Yongchel Ahn

Synthesis of diethylamino-curcumin mimics with substituted triazolyl groups and their sensitization effect of TRAIL against brain cancer cells.

A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone. In particular, 11a and 11j are promising candidates for TRAIL-sensitizers with potential use in combination chemotherapy for brain tumors.

Efficacy of Fulvestrant in Heavily Pretreated Postmenopausal Women with Advanced Breast Cancer: A Preliminary Report

Purpose Fulvestrant, a potent estrogen receptor (ER) antagonist with a novel mechanism of action, has shown efficacy in pretreated patients with advanced breast cancer. We assessed the efficacy and tolerability of fulvestrant in Korean postmenopausal women. Methods Of the 25 candidates identified at Asan Medical Center, Seoul, Korea, six were deemed ineligible due to inadequate baseline and follow-up imaging. The 19 patients included in this retrospective analysis received the approved dose of fulvestrant (250 mg intramuscular injection, once per month) as second- (n=8), third- (n=7), or fourth-line (n=4) endocrine therapy. Results At a median follow-up of 7.4 months (range, 1.2-34.8 months), the 19 patients received a median of four cycles (range, 1-34 cycles) of fulvestrant. Median time to progression was 5.5 months (95% confidence interval [CI], 0.4-10.7 months), and median overall survival was 17.9 months (95% CI, 2.7-33.1 months). Among 17 evaluable patients, one (5.3%) achieved a partial response, 10 (52.6%) showed stable disease, and six (31.6%) showed progressive disease. The clinical benefit rate was 26.3%. Four patients (21.1%) reported adverse events, but all were grade 1 or 2. Conclusion Fulvestrant was effective and well tolerated in patients with advanced breast cancer who had been previously treated with several lines of endocrine and chemotherapeutic agents.

Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells

Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway.

Prognostic Implications of Primary Tumor Resection in Stage IVB Colorectal Cancer in Elderly Patients.

Purpose The aim of this study was to identify prognostic factors in stage IVB colorectal cancer in elderly patients, focusing on the influence of treatment modalities, including palliative chemotherapy and primary tumor resection. Methods A cohort of 64 patients aged over 65 years who presented with stage IVB colorectal cancer at the Gangneung Asan Hospital between July 1, 2001, and December 31, 2009, was analyzed. Demographics, tumor location, tumor grade, performance status, levels of carcinoembryonic antigen (CEA), level of aspartate aminotransferase (AST), and distant metastatic site at diagnosis were analyzed. Using the treatment histories, we analyzed the prognostic implications of palliative chemotherapy and surgical resection of the primary tumor retrospectively. Results The cohort consisted of 30 male (46.9%) and 34 female patients (53.1%); the median age was 76.5 years. Primary tumor resection was done on 28 patients (43.8%); 36 patients (56.2%) were categorized in the nonresection group. The median survival times were 12.43 months in the resection group and 3.58 months in the nonresection group (P < 0.001). Gender, level of CEA, level of AST, Eastern Cooperative Oncology Group performance status, tumor location, and presence of liver metastasis also showed significant differences in overall survival. On multivariate analysis, male gender, higher level of CEA, higher AST level, and no primary tumor resection were independent poor prognostic factors. In particular, nonresection of the primary tumor was the most potent/poor prognostic factor in the elderly-patient study group (P = 0.001; 95% confidence interval, 2.33 to 21.99; hazard ratio, 7.16). Conclusion In stage IVB colorectal cancer in elderly patients, resection of the primary tumor may enhance survival.

Primary esophageal mucosa-associated lymphoid tissue lymphoma diagnosed by using stacked forceps biopsy.

Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case.

Diethylamino-curcumin mimic with trizolyl benzene enhances TRAIL-mediated cell death on human glioblastoma cells

BackgroundsGlioblastoma multiforme is one of the most aggressive human malignant brain tumors. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known as the death ligand, which induces preferential apoptosis of transformed cancer cells. In this study, we demonstrated that the newly synthesized diethylamino-curcumin mimic with trizolyl benzene (YM-4) enhances cytotoxicity in combination with TRAIL in human glioblastoma cells.MethodsWe synthesized diethylamino-curcumin mimic with trizolyl benzene (YM-4) and investigated possible apoptotic cell signaling by co-treatment with YM-4 and TRAIL on human glioblastoma cells.ResultsCaspase-8, 9, and 3 and poly (ADP-ribose) polymerase were more efficiently cleaved with cotreatment of YM-4 and TRAIL than treatment with each alone in human glioblastoma cells. Co-treatment with YM-4 and TRAIL significantly increased the expression of Bax and Smac/Diablo and also inhibited the expression of the X-linked inhibitor of apoptosis protein and Survivin in human glioblastoma cells.ConclusionThese results demonstrated that YM-4 can be an anticancer candidate that can be effective on human glioblastoma cells in combination with TRAIL.

Practicality of using the figure-of-eight bandage to prevent fatal wound dehiscence after spinal tumor surgery for upper thoracic metastasis

Abstract Object: Serious postoperative wound problems can frequently develop after surgery with perioperative RT for upper thoracic metastatic lesions. The figure-of-eight bandage can restrict excessive shoulder motion, which could prevent wound dehiscence. The purpose of this study was to describe the efficacy of using the figure-of-eight bandage to prevent postoperative wound dehiscence. Methods: Between February 2005 and July 2015, we retrospectively evaluated the medical records of cancer patients who underwent surgery with or without RT for spinal metastasis involving the upper thoracic spine. From January 2009, all patients received figure-of-eight bandaging immediately postoperatively, which was then maintained for 2 months. The outcome measures were the incidence and successful management of wound dehiscence following application of the figure-of-eight bandage. Results: One hundred and fifteen patients (71 men and 44 women) were enrolled in the present study. A figure-of-eight bandage in conjunction with a thoracolumbosacral orthosis (TLSO) was applied to 78 patients, while only TLSO was applied to 37 patients. The overall rate of wound dehiscence was 4.34% and the mean duration before wound dehiscence was 27.0 days (range, 22–31 days) after surgery. In the TLSO-only group, wound dehiscence occurred in four patients (10.81%), meanwhile there was only one case (1.33%) of wound dehiscence in the group that had received the figure-of-eight bandage with TLSO. Three of four patients with wound dehiscence in the TLSO only group died from unresolved wound problems and another patient was treated with wound closure followed by the application of the figure-of-eight bandage. The only patient with wound dehiscence among the patients who received both the figure-of-eight bandage and TLSO was managed by primary wound closure without further complication. Conclusion: Current study suggests that the figure-of-eight bandage could prevent wound dehiscence and be used to treat wound problems easily.

Multidisciplinary approach for treatment of primary hepatic choriocarcinoma in adult male patient

Choriocarcinoma is a rare malignant germ cell tumor and it usually occurs in the gonads (ovary or testis) and uterus. Primary hepatic choriocarcinoma (PHC) is a variant of choriocarcinoma featuring sole liver presentation without any evidence of gonodal involvements. Adult male patients with PHC carry dismal prognosis and their median survival period was less than 5 months. We herein present a first Korean case of a 54-year-old male patient with adult PHC, who was treated by surgical resection and chemotherapy through a multidisciplinary approach.

Primary central nervous system lymphoma: a new prognostic model for patients with diffuse large B-cell histology

Background Age and performance status are important prognostic factors in primary central nervous system (CNS) lymphoma. Although several prognostic models have been proposed, there is no consensus on the optimal model for patients with diffuse large B-cell histology. Methods Seventy-seven patients with primary CNS diffuse large B-cell lymphoma were retrospectively analyzed to determine factors affecting survival. Three Western models were applied to our eligible patients; we devised a novel model based on our findings. Results The median patient age was 59 years (range, 29–77); the median event-free and overall survival (OS) durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and Memorial Sloan Kettering Cancer Center models were applicable to our cohorts. Multivariate analysis showed that advanced age, multifocal lesions, and high cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A novel model for predicting prognosis was then developed based on these variables. Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3 were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very high-risk groups (N=4), respectively. Sixty-one patients were eligible considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the low-, moderate-, high-, and very high-risk groups, respectively (P<0.01). Conclusion Advanced age, multifocal lesions, and high CSF protein concentration were adversely related with prognosis. Our model can be helpful in pre-treatment risk stratification for patients with primary CNS lymphoma with diffuse large B-cell histology.

O1-6-3Novel curcumin mimics: Potential anticancer drugs against human glioblastoma multiforme

Yongchel Ahn, Cheon-Soo Park, HyukJai Jang, JiHwan Lee, Mikyong Byun, Byung-Gon Park, Woon-Seob Shin, Yoon-Sun Park, Seokjoon Lee, Daeho Kwon Department of Hematology and Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Korea, Department of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Medical Research Center, Gangneung Asan Hospital, University of Ulsan College of Medicine, Department of Nursing, Korea University College of Nursing, Department of Physiology, Catholic Kwandong University College of Medicine, Department of Pharmacology, Catholic Kwandong University College of Medicine, Department of Microbiology, Catholic Kwandong University College of Medicine