Purpose: Cervical cancer that is invisible on magnetic resonance imaging (MRI) may suggest lower tumor burden than physical examination. Recently, 3 tesla (3T) MRI has been widely used prior to surgery because of its higher resolution... more
Purpose: Cervical cancer that is invisible on magnetic resonance imaging (MRI) may suggest lower tumor burden than physical examination. Recently, 3 tesla (3T) MRI has been widely used prior to surgery because of its higher resolution than 1.5T MRI. The aim was to retrospectively evaluate the utility of 3T MRI in women with early cervical cancer in determining the necessity of less invasive surgery. Materials and methods: Between January 2010 and December 2015, a total of 342 women with FIGO stage IB1 cervical cancer underwent 3T MRI prior to radical hysterectomy, vaginectomy, and lymph node dissection. These patients were classified into cancer-invisible (n = 105) and cancer-visible (n = 237) groups based on the 3T MRI findings. These groups were compared regarding pathologic parameters and long-term survival rates. Results: The cancer sizes of the cancer-invisible versus cancer-visible groups were 11.5 ± 12.2 mm versus 30.1 ± 16.2 mm, respectively (p < 0.001). The depths of str...
Research Interests:
PurposeThis study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent... more
PurposeThis study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.Materials and MethodsWe conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.ResultsAmong 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38....
Research Interests:
ObjectiveBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in several... more
ObjectiveBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in several cancers, the objective of this study was to investigate BRCA1 expression using immunohistochemistry (IHC) in cervical cancer and its possible prognostic relevance.MethodsSeventy patients with cervical cancer were enrolled in this study. Samples from each tumor were stained for BRCA1 and reviewed independently by gynecologic pathologists blinded to the BRCA status. Kaplan–Meier methods were used to estimate overall survival according to BRCA1 expression. Differentially expressed genes (DEGs) by BRCA1 expression were selected using GSE44001 dataset, which included 300 samples treated with radical hysterectomy. In addition, cox regression analysis with backward elimination was performed to select independent prognostic markers. Gene set enrichment analysis (...
Research Interests:
Research Interests:
Research Interests:
Ovarian cancer is an intractable disease because patients with ovarian cancer frequently develop drug resistance after long-term chemotherapy. Despite the availability of cumulative information on drug-resistant patients, strategies to... more
Ovarian cancer is an intractable disease because patients with ovarian cancer frequently develop drug resistance after long-term chemotherapy. Despite the availability of cumulative information on drug-resistant patients, strategies to reverse drug resistance have still not been established. In this study, we analyzed drug resistance-associated transcription factors (TFs) in ovarian cancer. Gene expression profiles of 15 drug-resistant and 11 drug-sensitive patients with ovarian cancer were compared. Our results showed that TFs TFEB1 and YEATS4 regulated the expression of downstream target genes. These 2 TFs have already been implicated in tumorigenesis or metastasis. To our knowledge, this is the first study to evaluate the involvement of these TFs in drug resistance of ovarian cancer. Interestingly, 70% knockdown of each of these TFs with siRNAs resulted in approximately 20%~30% recovery of drug sensitivity. Further, combination treatment of ovarian cancer cells with TFEB1 and YEA...
Research Interests: Metastasis, Cancer Research, Ovarian Cancer, Transcription Factors, Medicine, and 13 moreWestern blotting, Signal Transduction, Drug, Transcriptome, Humans, Female, Drug Resistance, Transcription Factor, Carcinogenesis, Gene expression profiling, real time polymerase chain reaction, reverse transcriptase polymerase chain reaction, and Ovarian Neoplasms
The aim of this study was to investigate outcomes in uterine cancer patients undergoing pulmonary metastasectomy and prognostic factors associated with survival after the procedure. A retrospective study was performed in 29 uterine cancer... more
The aim of this study was to investigate outcomes in uterine cancer patients undergoing pulmonary metastasectomy and prognostic factors associated with survival after the procedure. A retrospective study was performed in 29 uterine cancer patients who underwent surgical resection of pulmonary metastatic lesions at Samsung Medical Center between June 1995 and December 2011. Histopathology showed carcinoma in 17 patients (58.6%) and sarcoma in 12 patients (41.4%). Of the 29 patients, 17 patients (58.6%) had less than three pulmonary metastatic lesions. Eight patients (27.6%) had symptoms related to lung metastasis. The five-year survival rate after pulmonary metastasectomy for the entire cohort was 48.2%. On univariate and multivariate analysis, the presence of pulmonary symptoms and more than three lesions of metastasis were associated with poor survival after pulmonary metastasectomy. Pulmonary metastasectomy for uterine cancer is an acceptable treatment in selected patients. Patien...
Research Interests:
Research Interests:
The aim of this study was to assess the efficacy and safety of laparoscopic treatment for adnexal cystic masses that were predicted to be benign in postmenopausal women. Postmenopausal women found to have an adnexal cystic mass were... more
The aim of this study was to assess the efficacy and safety of laparoscopic treatment for adnexal cystic masses that were predicted to be benign in postmenopausal women. Postmenopausal women found to have an adnexal cystic mass were retrospectively evaluated with transvaginal ultrasonography, and serum CA-125 levels. The selection criteria were adnexal cystic masses greater than 3 cm but less than 10 cm, the masses were in the benign range (4-8) of Sassone's scoring system for transvaginal ultrasonography, and the patients had serum CA-125 levels less than 65 IU/mL. Two hundred nineteen women fulfilled the criteria and underwent operative laparoscopy. Almost all the masses (99.5%) were accurately predicted to be benign except for one borderline ovarian tumor. Two hundreds thirteen (97.3%) women were successfully managed by operative laparoscopy and six (2.7%) required laparotomy. For the patients managed by laparoscopy, the mean operative time was 51.3 min; the mean hospital sta...
Research Interests:
This study was designed to compare survival outcomes of patients with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CC) to those of patients with grade 3 endometrioid carcinoma (G3EC) according to 1988 and 2009... more
This study was designed to compare survival outcomes of patients with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CC) to those of patients with grade 3 endometrioid carcinoma (G3EC) according to 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems. We retrospectively reviewed all patients with endometrial cancer treated at a single institution between 1995 and 2009. Among the 647 patients with endometrial cancer, 51 with G3EC and 46 with UPSC and CC histology were confirmed. 1988 FIGO stage, 2009 FIGO stage, and extrauterine metastasis were significantly different between the UPSC and CC group and G3EC group (p=0.002, p=0.041, and p=0.020, respectively). Restaging from the 1988 FIGO to the 2009 FIGO criteria increased the number of stage I cases by 10 (11.0%). Overall, 8 in the UPSC and CC and 2 in the G3EC group were down-staged to stage I. In the UPSC and CC group, the 3-year overall survival for 1988 FIGO stage I was 92...
Research Interests:
Research Interests: Oncology, Cancer, Medicine, Korean, Internal Medicine, and 3 moreCervical Cancer, Cervix, and Adenocarcinoma
This study aimed to identify features on preoperative computed tomography (CT) scans that are predictive of suboptimal primary cytoreduction and to evaluate the correlation between CT findings and intraoperative findings in advanced... more
This study aimed to identify features on preoperative computed tomography (CT) scans that are predictive of suboptimal primary cytoreduction and to evaluate the correlation between CT findings and intraoperative findings in advanced ovarian cancer. We retrospectively reviewed preoperative CT scans and operative findings from patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreduction between 2003 and 2006. Fourteen criteria were assessed. Clinical data were extracted from medical records. Residual tumors measuring ≥1 cm were considered suboptimal. We retrospectively identified 118 patients who met the study inclusion criteria. The rate of optimal cytoreduction (≤1 cm residual disease) was 40%. On preoperative CT scans, omental extension to the stomach or spleen and inguinal or pelvic lymph nodes >2 cm were predictors of suboptimal cytoreduction on univariate (p = 0.016 and p = 0.028, respectively) and multivariate analysis (p = 0.042 and p = 0.029, re...
Research Interests:
To discuss the feasibility of single-site robotic surgery for benign gynecologic tumors and early stage gynecologic cancers. In this single institution, prospective analysis, we analyzed six patients who had undergone single-site robotic... more
To discuss the feasibility of single-site robotic surgery for benign gynecologic tumors and early stage gynecologic cancers. In this single institution, prospective analysis, we analyzed six patients who had undergone single-site robotic surgery between December 2013 and August 2014. Surgery was performed using the da Vinci Si Surgical System. Patient characteristics and surgical outcomes were analyzed. Single-site robotic surgery was performed successfully in all six cases. The median patient age was 48 years, and the median body mass index was 25.5 kg/m² (range, 22 to 33 kg/m²). The median total operative time was 211 minutes, and the median duration of intracorporeal vaginal cuff suturing was 32 minutes (range, 22 to 47 minutes). The median duration of pelvic lymph node dissection was 31 minutes on one side and 27 minutes on the other side. Patients' postoperative courses were uneventful. The median postoperative hospital stay was 4 days. No postoperative complications occurr...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Aim: To evaluate prognostic factors in Korean patients with endometrial cancer. Methods: A retrospective analysis was conducted on 248 patients who were staged surgically at the Samsung Medical Center between 1995 and 2004. Survival data... more
Aim: To evaluate prognostic factors in Korean patients with endometrial cancer. Methods: A retrospective analysis was conducted on 248 patients who were staged surgically at the Samsung Medical Center between 1995 and 2004. Survival data were analyzed using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression method. Results: The median age was 51 years (range 21–75), which was younger than in previous studies in Western patients, and the age of 50 years was the cutoff to predict survival. More than half (55.6%) were normal weight or underweight (BMI <25). Multivariate analysis revealed that age, Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage, and histopathology were independent predictors of disease-free survival, and FIGO stage and p53 mutation were independent prognostic factors for disease-specific survival (DSS). The 5-year DSS for patients with stage I, II, III and IV disease was 95.6, 93.8, 69.8 and 50%, respectiv...
Research Interests: Gastroenterology, Membrane Proteins, Medicine, Multivariate Analysis, Endometrial Cancer, and 15 moreHumans, Internal Medicine, Mutation, Female, Republic of Korea, Aged, Middle Aged, Gynecology, Neoplasm Invasiveness, Adult, Proportional Hazards Models, Disease Free Survival, Neoplasm staging, Paediatrics and reproductive medicine, and Endometrial neoplasms
Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we... more
Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Animal experiment of selenium with paclitaxel was performed using SKOV3ip1 cells in nude mice to evaluate their inhibiting effect for tumor growth. In addition, another animal experiment of paclitaxel with or without selenium was performed to assess the effect of survival and food intake in mice. The in vitro growth of selenium-treated cells was significantly decreased dose-dependently in A2780, HeyA8, and SKOV3ip1 cells. Therapy experiment in mice w...
Research Interests:
HER3 has been recognized to have an oncogenic role in various types of cancer. However, its prognostic significance has not been elucidated in cervical cancer. The aim of this study was to investigate the prognostic significance of HER3... more
HER3 has been recognized to have an oncogenic role in various types of cancer. However, its prognostic significance has not been elucidated in cervical cancer. The aim of this study was to investigate the prognostic significance of HER3 expression in cervical cancer using immunohistochemistry (IHC). HER3 immunohistochemical staining was performed on the tumor tissue samples of 336 cervical cancer patients. The association between the clinicopathological characteristics and patient survival analysis was assessed according to HER3 expression. HER3 IHC staining was positive in 31.0% (104/336) of the cervical cancer patients. A higher proportion of adeno-/adenosquamous carcinoma was observed in the HER3-positive group (34.6%) than in the HER3-negative group (18.8%). In survival analysis, HER3 expression was significantly associated with poorer disease-free survival (DFS) and overall survival (OS) (p < 0.001 and p = 0.002, respectively). Multivariate analysis also indicated that HER3 ...
Research Interests:
To support the implementation of genome-based precision medicine, we developed machine learning models that predict the recurrence of patients with gynecologic cancer in using immune checkpoint inhibitors (ICI) based on clinical and... more
To support the implementation of genome-based precision medicine, we developed machine learning models that predict the recurrence of patients with gynecologic cancer in using immune checkpoint inhibitors (ICI) based on clinical and pathologic characteristics, including Lynch syndrome-related screening markers such as immunohistochemistry (IHC) and microsatellite instability (MSI) tests. To accomplish our goal, we reviewed the patient demographics, clinical data, and pathological results from their medical records. Then we identified seven potential characteristics (four MMR IHC [MLH1, MSH2, MSH6, and PMS2], MSI, Age 60, and tumor size). Following that, predictive models were built based on these variables using six machine learning algorithms: logistic regression (LR), support vector machine (SVM), naive Bayes (NB), random forest (RF), gradient boosting (GB), and extreme gradient boosting (EGB) (XGBoost). The experimental results showed that the RF-based model performed best at pre...
Research Interests:
Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6... more
Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6 consecutive patients with PSTT treated in our institution. The electronic medical record database of Samsung Medical Center was screened to identify patients with PSTT from 1994 to 2017. Medical records for the details of each patient's clinical features and treatment were extracted and reviewed. This study was approved Institutional Review Board of our hospital. A total of 418 cases of GTD, 6 (1.4%) patients with PSTT were identified. The median age of the patients was 31 years. The antecedent pregnancy was term in all 5 cases with available antecedent pregnancy information and the median interval from pregnancy to diagnosis of PSTT was 8 months. The median titer of serum beta human chorionic gonadotropin (β-hCG) at diagnosis was 190.9 mIU/mL. Five...
Research Interests:
This retrospective study is to evaluate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with... more
This retrospective study is to evaluate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least one chemotherapy regimen were to receive etoposide at a dose of 100 mg/m/day intravenous (IV) on days 1 to 3 in combination with ifosfamide 1 g/m/day IV on days 1 to 5, every 21 days. From August 2008 to August 2016, 66 patients were treated with ETI regimen. Most patients were heavily pretreated prior to ETI: 53 (80.3%) patients had received 3 or more chemotherapy regimens. The response rate (RR) of ETI chemotherapy was 18.2% and median duration of response was 6.8 months (range, 0-30). Median survival of all patients was 5 months at a median follow up of 7.2 months. Platinum-free interval (PFI) more than 6 months prior to ETI has statistically significant correlation with overall survi...
Research Interests:
We investigated the feasibility of dynamin 2 as a potential treatment target in cervical cancer cells. We performed tissue microarray for dynamin 2 expression in 208 patients with early cervical cancer and in vitro in HeLa cells with... more
We investigated the feasibility of dynamin 2 as a potential treatment target in cervical cancer cells. We performed tissue microarray for dynamin 2 expression in 208 patients with early cervical cancer and in vitro in HeLa cells with dynamin 2 inhibitors MiTMAB, OcTMAB, Dynasore, and DD-6. Tumor size greater than 2 cm or tumor invasion of more than half of the entire cervix was associated with expression of dynamin 2 compared to no expression (p=0.013, and p=0.045, respectively). All dynamin 2 inhibitors significantly reduced proliferation, increased apoptotic activity, and reduced matrix metallopeptidase 9 expression in HeLa cells. Dynasore and DD-6 reduced migration of HeLa cells on laminin 1-coated plates and DD-6 most strongly reduced migration performance on fibronectin-coated plates. Targeting dynamin 2 may be a promising new approach for the treatment of cervical cancer.
Research Interests:
The purpose of this study was to analyze clinical outcomes from cervical cancer and stratify patients into risk groups for prognostic factors for early-stage disease. We retrospectively reviewed patients with stage IB or IIA cervical... more
The purpose of this study was to analyze clinical outcomes from cervical cancer and stratify patients into risk groups for prognostic factors for early-stage disease. We retrospectively reviewed patients with stage IB or IIA cervical cancer treated with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) following primary surgery at Samsung Medical Center from 2001 to 2011. Adjuvant RT was added for patients with intermediate-risk factors, and adjuvant CCRT was performed on high-risk patients after surgery. We reviewed 247 patients-149 in the high-risk group and 98 in intermediate-risk group. The median follow-up was 62 months. Loco-regional failure (LRF) alone occurred in 7 patients (2.8%), distant metastasis alone in 37 patients (15.0%) and LRF with DM in 4 patients (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates for both groups were 79.7% and 87.6%, respectively. In the high-risk group, the 5-year DFS and OS probabilities were 72.5% an...
Research Interests:
Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The... more
Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received a...
Research Interests:
Magnetic resonance imaging (MRI) is useful for staging endometrial cancer. The treatment and prognosis of MRI-invisible endometrial cancer remain unclear. The purpose of this study was to retrospectively evaluate the long-term outcomes of... more
Magnetic resonance imaging (MRI) is useful for staging endometrial cancer. The treatment and prognosis of MRI-invisible endometrial cancer remain unclear. The purpose of this study was to retrospectively evaluate the long-term outcomes of patients with MRI-invisible endometrial cancer. Between February 1995 and December 2011, we reviewed the medical records of 433 patients with endometrial cancer, which was staged IA on MRI. Of these patients, 89 had MRI-invisible cancer and 344 had MRI-visible cancer. Both cancers were treated with simple hysterectomy with or without lymph node dissection according to the surgeon's decision. Both cancers were compared regarding pathologic findings, recurrence rates, and survival rates. The median sizes of MRI-invisible and MRI-visible cancers were 4 mm (0 to 40 mm) and 20 mm (0 to 89 mm), respectively (p<0.001). Myometrial invasion of these groups were detected in 20.2% (18/89) and 56.7% (195/344), respectively (p<0.001). Lymphadenectomy ...
Research Interests:
Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed... more
Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (...
Research Interests:
Research Interests:
Research Interests:
Primary vaginal cancer represents only 1% to 2% of malignant neoplasm of the female genital tract. Here, we report a 68-year-old woman who showed a vaginal tumor extending to urethra and clitoris, a 10 cm-sized mass in left adnexa and... more
Primary vaginal cancer represents only 1% to 2% of malignant neoplasm of the female genital tract. Here, we report a 68-year-old woman who showed a vaginal tumor extending to urethra and clitoris, a 10 cm-sized mass in left adnexa and multiple metastases in lung and liver. Vaginal biopsy showed squamous cell carcinoma of vagina and she was diagnosed as International Federation of Gynecology and Obstetrics stage IVB vaginal cancer. Palliative surgery including left salpingectomy, tumorectomy, and clitoris mass excision was performed. Concurrent chemoradiation therapy (CCRT) with six cycles of 5-fluorouracil and cisplatin was administered. The patient had a complete remission of 20 months after treatment. At a 40-month follow-up, there was no evidence of local recurrence or distant metastasis. We can suggest that CCRT is very effective in treating primary squamous cell carcinoma of the vagina, not only in locally advanced but also systemically involved vaginal cancer in selected cases.
Research Interests:
Research Interests:
Research Interests:
The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the... more
The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the workshop, and the up-to-date findings on the management of gynecologic cancers were presented and discussed. This meeting focused on the new trends in the management of cervical cancer, fertility-sparing management of gynecologic cancers, surgical management of gynecologic cancers, and recent advances in translational research on gynecologic cancers.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Gastroenterology, Medicine, Multivariate Analysis, Humans, Internal Medicine, and 15 moreGynecologic Oncology, Female, Cervical Cancer, Aged, Middle Aged, Adult, Monocytes, Prognosis, Cancer Incidence, Gynecologic, Disease Free Survival, Neoplasm staging, Monocyte, Paediatrics and reproductive medicine, and leukocyte Count
Research Interests: Obstetrics, Surgery, Cancer, Treatment, Chemotherapy, and 15 moreTreatment Outcome, Medicine, Humans, Female, European, Gynecology, Survival Rate, Prognosis, Ovary, Stomach, Proportional Hazards Models, Stomach neoplasms, Paediatrics and reproductive medicine, Colonic Neoplasms, and Ovarian Neoplasms
Purpose: Src is an attractive target because it is overexpressed in a number of malignancies, including ovarian cancer. However, the effect of Src silencing on other Src family kinases (SFKs) is not known. We hypothesized that other SFK... more
Purpose: Src is an attractive target because it is overexpressed in a number of malignancies, including ovarian cancer. However, the effect of Src silencing on other Src family kinases (SFKs) is not known. We hypothesized that other SFK members could compensate for the lack of Src activity.Experimental Design: Cell viability after either Src or Fgr silencing was examined in ovarian cancer cell lines by MTT assay. Expression of SFKs after Src silencing in ovarian cancer cells was examined by real-time reverse transcriptase (RT)-PCR. Therapeutic effect of in vivo Src and/or Fgr silencing was examined using siRNA incorporated into chitosan nanoparticles (siRNA/CH-NP). Microvessel density, cell proliferation, and apoptosis markers were determined by immunohistochemical staining in ovarian tumor tissues.Results: Src silencing enhanced cytotoxicity of docetaxel in both SKOV3ip1 and HeyA8 cells. In addition, Src silencing using siRNA/CH-NP in combination with docetaxel resulted in signific...
Research Interests:
The purpose of this study was to assess the efficacy and toxicity of capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The chemotherapy... more
The purpose of this study was to assess the efficacy and toxicity of capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The chemotherapy regimen consisted of capecitabine 1250 mg/m(2) orally twice a day on day 1 to day 14 and cisplatin 60 mg/m(2) i.v. on day 1. Each cycle was repeated every 3 weeks up to a maximum of six cycles. By intent-to-treat analysis, the overall response rate was 50% [complete response, 0/36; partial response, 18/36; 95% confidence interval (CI) 32% to 67%]. The median progression-free survival was 3.7 months (95% CI 2.1-5.3 months), and the median response duration was 4.9 months. The median overall survival and 1-year survival rate were 10.3 months (95% CI 8.5-12.1 months) and 43.3%, respectively. The common grade 3 or 4 nonhematologic adverse events were anorexia (8.8%), fatigue (4.4%), diarrhea (4.4%), stomatitis (3.6%), and the hand-foot syndrome (1.5%). The most common grade 3 or 4 hematologic adverse event was neutropenia (14.6%), followed by anemia (1.5%). There was no treatment-related death. The XP combination regimen has antitumor activity and acceptable safety profile in patients with metastatic or recurrent SCCHN.
Research Interests:
Purpose: Bromodomain-containing protein 7 (BRD7), which is a subunit of SWI/SNF complex, has been recently suggested as a novel tumor suppressor in several cancers. In this study, we investigated the tumor suppressive effect of BRD7 in... more
Purpose: Bromodomain-containing protein 7 (BRD7), which is a subunit of SWI/SNF complex, has been recently suggested as a novel tumor suppressor in several cancers. In this study, we investigated the tumor suppressive effect of BRD7 in epithelial ovarian cancer. Experimental Design: We analyzed the expression of BRD7 in human ovarian tissues with real-time PCR. To investigate the functional role of BRD7, we transfected ovarian cancer cells (A2780 and SKOV3) with BRD7 plasmid and checked the cell viability, apoptosis, and invasion. The activities of BRD7 in the signaling pathways associated with carcinogenesis were also tested. In addition, we used the orthotopic mouse model for ovarian cancer to evaluate tumor growth-inhibiting effect by administration of BRD7 plasmid. Results: The BRD7 expression was downregulated in the ovarian cancer tissues compared with normal (P < 0.05), high-grade serous cancer exhibited significantly decreased expression of BRD7 compared with low-grade (P...
Research Interests: Flow Cytometry, Biology, Cancer Research, Ovarian Cancer, Apoptosis, and 13 moreMedicine, Cell separation, Humans, Mice, Female, Animals, Carcinogenesis, Ovarian Carcinoma, Transfection, Enzyme Linked Immunosorbent Assay, real time polymerase chain reaction, reverse transcriptase polymerase chain reaction, and Ovarian Neoplasms
Purpose: EphA2 overexpression is frequently observed in endometrial cancers and is predictive of poor clinical outcome. Here, we use an antibody drug conjugate (MEDI-547) composed of a fully human monoclonal antibody against both human... more
Purpose: EphA2 overexpression is frequently observed in endometrial cancers and is predictive of poor clinical outcome. Here, we use an antibody drug conjugate (MEDI-547) composed of a fully human monoclonal antibody against both human and murine EphA2 (1C1) and the tubulin polymerization inhibitor monomethylauristatin F. Experimental Design: EphA2 expression was examined in endometrial cancer cell lines by Western blot. Specificity of MEDI-547 was examined by antibody degradation and internalization assays. Viability and apoptosis were investigated in endometrial cancer cell lines and orthotopic tumor models. Results: EphA2 was expressed in the Hec-1A and Ishikawa cells but was absent in the SPEC-2 cells. Antibody degradation and internalization assays showed that the antibody drug conjugate decreased EphA2 protein levels and was internalized in EphA2-positive cells (Hec-1A and Ishikawa). Moreover, in vitro cytotoxicity and apoptosis assays showed that the antibody drug conjugate d...
Research Interests: Biology, Cancer Research, Apoptosis, Medicine, Western blotting, and 15 moreEndometrial Cancer, Internalization, Humans, Mice, Endocytosis, Female, Animals, Monoclonal Antibodies, Fluorescent Antibody Technique, Antibody, Endometrial carcinoma, Monoclonal Antibody, Cell Proliferation, Cell Survival, and Endometrial neoplasms
Research Interests:
We previously showed that PAUF is involved in tumor development and metastases in cervical cancer. This study was conducted to discover novel molecular markers linked with PAUF in cervical cancer using genomic network analysis and to... more
We previously showed that PAUF is involved in tumor development and metastases in cervical cancer. This study was conducted to discover novel molecular markers linked with PAUF in cervical cancer using genomic network analysis and to assess their prognostic value in cervical cancer. Three PAUF-related genes were identified using network-based analysis of the open genome datasets. To assess the expression of these genes and their relationship to the outcome of cervical cancer, immunohistochemical analysis was performed using cervical cancer TMA. The associations of the identified proteins with clinicopathologic characteristics and prognosis were examined. AGR2, BRD7, and POM121 were identified as interconnected with PAUF through network-based analysis. AGR2 ( = 0.213, < 0.001) and POM121 ( = 0.135, = 0.013) protein expression were positively correlated with PAUF. BRD7 and AGR2 were significantly associated with favorable disease-free survival (DFS) ( = 0.009 and < 0.001, respec...
Research Interests:
Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular... more
Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscapes of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared with the traditional long-term cultured cancer cell line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. Here, we provide insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors, and the potential repurposing of ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present a potential...
Research Interests:
Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important... more
Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells. This study aimed to improve targeted delivery and enhance therapeutic efficacy for tumor anti-angiogenesis. The HA-CH-NP/siRNA was 200 ± 10 nm in size with a zeta potential of 26.4 mV. The loading efficiency of siRNA to the HA-CH-NP/siRNA was up to 60%. The selective binding of HA-CH-NP/siRNA to CD44-positive tumor endothelial cells increased by 2.1-fold compared with that of the CD44 nontargeted CH-NP/siRNA. PLXDC1 silencing by the HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor-bearing mice compa...
Research Interests: Biochemistry, Chemistry, Cancer, Chitosan, Drug delivery, and 15 moreCell Biology, Cancer Research, Apoptosis, Angiogenesis, Cell line, Endothelial Cells, Female, Animals, Drug Delivery Systems, CD, Cell Proliferation, Antineoplastic Agents, Chitosan Nanoparticles, epithelial ovarian cancer, and Angiogenesis inhibitors
This study aims to analyze the published literatures on the effect of less radical fertility-preserving procedures, such as conization or simple trachelectomy, on oncological outcomes in IA1 cervical cancer patients with lymphovascular... more
This study aims to analyze the published literatures on the effect of less radical fertility-preserving procedures, such as conization or simple trachelectomy, on oncological outcomes in IA1 cervical cancer patients with lymphovascular space invasion (LVSI) through a systematic-review. The EMBASE and MEDLINE databases and Cochrane Library were searched for published studies reporting the oncological outcomes of conization/simple trachelectomy in these patients, through April 2017. The endpoints were recurrence and mortality rates. Data were presented as per the Meta-analysis Of Observational Studies in Epidemiology checklist. Practice guidelines were generated via the Grading of Recommendation, Assessment, Development and Evaluation system. From 6,755 records, 94 full-texts articles were reviewed for eligibility, and five studies were included in this systematic review. All included studies were nonrandomized studies: two case-control studies comparing conization (n = 14) with hyste...
Research Interests:
This study was done to evaluate whether perioperative propranolol (ß-blocker) in ovarian cancer patients undergoing debulking surgery reduced perioperative tumor growth induced by surgical stress. This was a prospective randomized single... more
This study was done to evaluate whether perioperative propranolol (ß-blocker) in ovarian cancer patients undergoing debulking surgery reduced perioperative tumor growth induced by surgical stress. This was a prospective randomized single institution analysis. The primary objective was to compare the changes in CA 125 level (changes between preoperation day 2 and postoperative day 7). As a study arm, patients received a low dose of propranolol 40 mg/day (4×10 mg) starting two days before surgery and 40 mg twice daily for three days following surgery. Twenty-two patients were enrolled and 16 were evaluable for efficacy. The drug was well tolerated. The mean decrease of CA 125 during the seven perioperative days was 83.1±8.9% in the propranolol group and 72.4±14.7% in the placebo group. The difference was statistically significant (P=0.044). The change of C-reactive protein, cortisol, and anxiety score (State-Trait Anxiety Inventory-X1) were not different between the two groups. This p...
Research Interests:
We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome... more
We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation, we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and 7 methylated DNAs from primary EOC tissues that predicted lymphatic invasion, and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic r...
Research Interests:
This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer. The expression of V-ATPase was evaluated in 351... more
This study was conducted to investigate whether a proton pump inhibitor (PPI) could enhance chemosensitivity via the inhibition of vacuolar-type H+ ATPase (V-ATPase) in cervical cancer. The expression of V-ATPase was evaluated in 351 formalin-fixed, paraffin-embedded human cervical cancer tissues using immunohistochemistry and compared with clinicopathologic risk factors for disease prognosis. The influence of cell proliferation and apoptosis following V-ATPase siRNA transfection or esomeprazole pretreatment was assessed in cervical cancer cell lines using MTT and ELSIA assay, respectively. Immunohistochemical analysis revealed that V-ATPase was expressed in about 60% of cervical cancer tissue samples (211/351), and the expression was predominantly found in adenocarcinoma histology (P=0.016). Among patients with initially bulky cervical cancer (n=89), those with V-ATPase expression had shorter disease-free survival (P=0.005) and overall survival (P=0.023). Co-treatment with V-ATPase...
Research Interests:
Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the... more
Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compa...