Jeong-Hee Lee

D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric Cancer Treated by Chemotherapy

Abstract Systemic activation of hemostasis and thrombosis has been implicated in tumor progression and metastasis. D-dimer has been used as an indicator for the thrombosis. Here, we investigated the role of the activation of coagulation in patients with metastatic gastric cancer by measuring D-dimer level. We conducted an observation study of 46 metastatic gastric cancer patients who received palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the first response evaluation after CTx. The overall survival (OS) of patients with pretreatment D-dimer levels <1.5 &mgr;g/mL was significantly longer than that of patients with D-dimer levels ≥1.5 &mgr;g/mL (22.0 vs 7.9 months, P = 0.019). At the first response evaluation, the mean level of D-dimer was significantly decreased by 2.11 &mgr;g/mL in patients either with partial response or stable disease (P = 0.011) whereas the mean level of D-dimer, although the difference did not reach statistical significance, was increased by 2.46 &mgr;g/mL in patients with progressive disease. In addition, the OS of patients with D-dimer levels <1.0 &mgr;g/mL at the first response evaluation was significantly longer than that of patients with D-dimer levels ≥1.0 &mgr;g/mL (22.0 vs 7.0 months, P = 0.009). The lower D-dimer levels (<1.0 &mgr;g/mL) at the first response evaluation after CTx was independent predictive factor for better survival in multivariate analysis (P = 0.037). This study suggests that D-dimer levels may serve as a biomarker for response to CTx and OS in patients with metastatic gastric cancer.

Population-Based Regional Cancer Incidence in Korea: Comparison between Urban and Rural Areas

Purpose The purpose of this study is to investigate differences in organ-specific cancer incidence according to the region and population size in Korea. Materials and Methods We reviewed the data of the cancer registration program of Gyeongnam Regional Cancer Center between 2008 and 2011. Age-standardized rates of cancer incidence were analyzed according to population size of the region and administrative zone. Results Incidence of thyroid cancer has been increasing rapidly in both urban and rural areas. However, the thyroid cancer incidence was much lower in rural areas than in urban areas and megalopolis such as Seoul. Gastric cancer was relatively more common in rural areas, in megalopolis near the sea (Ulsan, Busan, and Incheon), and other southern provinces (Chungcheongnam-do, Gyeongsangbuk-do, and Gyeongsangnam-do). A detailed analysis in Gyeongsangnam-do revealed that rural areas have relatively low incidence of thyroid and colorectal cancer, and relatively high incidence of gastric and lung cancer compared to urban areas. Conclusion This study suggests that there are some differences in cancer incidence by population size. Thyroid and colorectal cancer incidence was increasing, and gastric and lung cancer was slightly decreasing in urban areas, whereas gastric and lung cancer incidence still remains high in rural areas.

Cyclosporine A as a Primary Treatment for Panniculitis-like T Cell Lymphoma: A Case with a Long-Term Remission.

Subcutaneous panniculitis-like T cell lymphoma (SPTL) is a distinctive cutaneous lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic T cells, similar to panniculitis. It is well-established that patients who are diagnosed with SPTL usually respond poorly to chemotherapy, showing fatal outcome. As a first line treatment for SPTL, anthracycline-based chemotherapy was most frequently used. For the treatment of SPTL, the efficacy of cyclosporine A has been recently reported in relapsed SPTL after anthracycline-based chemotherapy. However, it is still not clear whether cyclosporine A can be used as a first-line treatment against SPTL. Here, we report a case of SPTL, which achieved complete remission for nine years after first-line cyclosporine A therapy. This study suggests that cyclosporine A can induce a complete long-term remission as a first-line treatment.

Tetraarsenic hexoxide demonstrates anticancer activity at least in part through suppression of NF-κB activity in SW620 human colon cancer cells

Tetraarsenic hexoxide (As4O6) has been used in Korean traditional medicine for the treatment of cancer since the late 1980s, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. Previous studies suggest that the As4O6-induced cell death pathway is different from that of As2O3 and its mechanism of anticancer activity remains unclear. Nuclear factor (NF)-κB is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Hence, in the present study, we investigated the effects of As4O6 on NF-κB activity and NF-κB-regulated gene expression in vitro and in vivo. The cytotoxicity assay revealed that As4O6 inhibited the growth of SW620 cells in a dose-dependent manner, and the half maximal inhibitory concentration (IC50) was ~1 µM after a 48 h treatment. As4O6 suppressed NF-κB activation and suppressed inhibitory κBα (IκBα) phosphorylation stimulated by tumor necrosis factor (TNF). As4O6 also suppressed downstream NF-κB-regulated proteins involved in cancer anti-apoptosis, proliferation, invasion and metastasis. In addition, As4O6 marginally suppressed tumor growth and the anti-NF-κB activity was confirmed using an in vivo xenograft mouse model in which animals were injected with SW620 cells. The present study provides evidence that As4O6 has anticancer properties through suppression of NF-κB activity and NF-κB-mediated cellular responses.

Programmed Death-Ligand 1 Expression and Its Correlation with Lymph Node Metastasis in Papillary Thyroid Carcinoma

Background The immunotherapeutic role of programmed death-ligand 1 (PD-L1) in life expectancy in many cancers has been highlighted. However, data regarding PD-L1 expression in papillary thyroid carcinoma (PTC) are limited. In this study, we describe the PD-L1 and programmed cell death protein 1 (PD-1) expressions in PTC and analyze their correlation with lymph node (LN) metastasis. Methods Clinicopathological data were obtained from 116 patients with PTC who were treated in Gyeongsang National University Hospital, Jinju, Korea in 2009. Tissue microarray blocks were made using representative paraffin blocks of classical PTCs excluding follicular variants. Two pathologists graded the proportion and intensity of PD-L1 and PD-1 expression in both tumor and inflammatory cells. According to their proportions, positive PTC cells were scored as negative (0%), grade 1 (1%–50%), and grade 2 (51%–100%). Similarly, positive inflammatory cells were graded as negative (0%), grade 1 (1%–10%), and grade 2 (11%–20%). The intensity of each protein expression was simplified as positive or negative. Results A statistically significant correlation exists between the proportions of PD-1 and PD-L1 expression both in papillary carcinoma (p=.001) and peritumoral lymphoid cells in the thyroid (p<.001). In addition, the proportion of PD-L1 expression in PTC cells was closely related to metastatic LNs (p=.036). Conclusions PD-L1 is a valuable predictive marker for LN metastasis in PTC. Immunomodulating therapies that inhibit PD-L1 might be an option for patients with LN metastasis.

15-Deoxy-Δ12,14-prostaglandin J2 prevents oxidative injury by upregulating the expression of aldose reductase in vascular smooth muscle cells

Abstract The omega-6 fatty acid derivative 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is believed to play a role in cellular protection against oxidative stress in diverse cell systems. However, the cellular mechanisms by which protection is afforded by 15d-PGJ2 are not fully elucidated in vascular smooth muscle cells (VSMCs). In this study, we report the finding that 15d-PGJ2 elicited a time and concentration- dependent increase in aldose reductase (AR) expression. This induction was independent of the activation of peroxisome proliferator- activated receptor γ. Inhibition of phosphatidylinositol 3-kinase (PI3K) significantly suppressed the increase in expression and promoter activity of AR induced by 15d-PGJ2. Luciferase reporter assays demonstrated that 15d-PGJ2 targets the multiple stress response regions comprising the antioxidant response element in the promoter of the AR gene. 15d-PGJ2-mediated induction of AR promoter activity was potentiated in the presence of nuclear factor-erythroid 2-related factor 2 (Nrf2), but not in cells expressing dominant negative Nrf2. Cells treated with 15d-PGJ2 were resistant to oxidant-induced apoptotic cell death by inhibiting production of reactive oxygen species. These effects were significantly attenuated in the presence of an AR inhibitor or small interfering RNA against AR, indicating that AR plays a protective role against oxidative injury. Taken together, these findings demonstrate that activation of PI3K by 15d-PGJ2 increases the expression of AR through Nrf2, and increased AR activity may function as an important cellular response against oxidative injury.

Response to concurrent chemoradiotherapy as a prognostic marker in elderly patients with locally advanced esophageal cancer.

AIMS AND BACKGROUND Little is known about chemoradiotherapy in elderly patients with locally advanced esophageal cancer. We compared the efficacy and toxicity of chemoradiotherapy in elderly and non-elderly patients with locally advanced esophageal cancer and determined the variables affecting the treatment outcome in the elderly patients with locally advanced esophageal cancer who had received chemoradiotherapy. METHODS Fifty-seven elderly patients (age ≥ 65 years) and 30 non-elderly patients (age <65 years) were reviewed retrospectively. RESULTS The median age of the elderly group was 69 years and in the non-elderly group, 56.5 years. Although treatment compliance appeared to be poor, the response rate and median survival were similar in both the groups (elderly versus non-elderly; 84.4% vs 87.5%, and 11.2 months vs 11.3 months) and so were G3/4 hematologic and non-hematologic toxicities. The treatment-related mortality of the elderly patients appeared to be higher than that of the non-elderly group (7.0% vs 3.3%), but did not reach statistical significance. In prognostic factor analysis, a major response to chemoradiotherapy was a good prognostic indicator in the elderly group (response versus non-response; median overall survival times of 19.5 vs 5.4 months, respectively, P <0.001). CONCLUSIONS The study suggests that chemoradiotherapy for locally advanced esophageal cancer in elderly patients, even though treatment compliance appears to be poor, is as safe and effective as in non-elderly patients and that the response to chemoradiotherapy is related to prognosis in elderly patients.

Cystic Meningiomas: Correlation between Radiologic and Histopathologic Features

Background Tumors with cysts often correlate with gliomas, metastatic tumors, or hemangioblastomas, which require differentiation. Methods Thirty-eight cases of cyst associated-meningioma based on preoperative radiologic studies and histologic confirmations were reviewed from November 1998 to July 2017. Results A total of 395 cases of meningioma were observed in the 20 years, and surgical treatment of intracranial meningioma was performed in 120 cases. Thirty-eight (9.6%) cases of cyst associated meningiomas were analyzed. Nauta type I was the most common type of cyst (39.5%) and the most frequent histopathological subtype was meningothelial type (36.8%). Conclusion Statistically there were no significant associations between meningioma histopathological type and associated cysts; however, the rate of World Health Organization grade II was higher in cyst associated meningiomas than in unrelated meningiomas. This correlation was weak, in accordance with the meningioma grade.

Can Thymidine Phosphorylase Be a Predictive Marker for Gemcitabine and Doxifluridine Combination Chemotherapy in Cholangiocarcinoma?: Case Series

AbstractUnresectable cholangiocarcinoma is poorly responded to chemotherapy, especially for the case refractory to gemcitabine and cisplatin. Here, we tested whether high expression of thymidine phosphorylase (TP) can be a predictive biomarker for the indicator for gemcitabine and doxifluridine combination chemotherapy in the cholangiocarcinoma refractory to gemcitabine and cisplatin.Immunohistochemical staining for TP was performed with a biopsy specimen. We accepted the result as positive when more than 10% of cancer cells were stained with moderate intensity.Here, we report 2 cases of TP-positive cholangiocarcinoma well controlled with gemcitabine and doxifluridine combination chemotherapy, which had been refractory to the first line treatment with gemcitabine and cisplatin combination chemotherapy.

Prognostic impact of Ki-67 in patients with gastric cancer—the importance of depth of invasion and histologic differentiation

Abstract Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic biomarker has not been established in gastric cancer. The present study was performed to investigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC). With tissue microarray for 320 patients with gastric cancer, we performed immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. For validation, we performed bootstrap resampling. The median follow-up duration was 72 months (range: 3–120 months). Ki-67-high group showed worse prognosis than Ki-67-low group in EGC (5-YSR, 78.9% vs 92.0%, P  =  .018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs 59.2%, P  =  .951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-high group was considerably worse than that for Ki-67-low group (5-YSR, 67.0% vs 94.4%, P  =  .012), but not in those with moderately differentiated (P  =  .504) and poorly differentiated histology (P  =  .905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r  =  0.215, P  =  .002). Multivariate analysis also revealed that the high-Ki-67 expression serves as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397–13.515, P  =  .011), especially in the well-differentiated histology, but not in all the patients (P  =  .171). Bootstrap resampling internally validated this result (P  =  .011). This study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC with well-differentiated histologic type.