Jin-Myung Jung

Perfusion MR Imaging in Gliomas: Comparison with Histologic Tumor Grade

Objective To determine the usefulness of perfusion MR imaging in assessing the histologic grade of cerebral gliomas. Materials and Methods In order to determine relative cerebral blood volume (rCBV), 22 patients with pathologically proven gliomas (9 glioblastomas, 9 anaplastic gliomas and 4 low-grade gliomas) underwent dynamic contrast-enhanced T2*-weighted and conventional T1- and T2-weighted imaging. rCBV maps were obtained by fitting a gamma-variate function to the contrast material concentration versus time curve. rCBV ratios between tumor and normal white matter (maximum rCBV of tumor / rCBV of contralateral white matter) were calculated and compared between glioblastomas, anaplastic gliomas and low-grade gliomas. Results Mean rCBV ratios were 4.90°±1.01 for glioblastomas, 3.97°±0.56 for anaplastic gliomas and 1.75°±1.51 for low-grade gliomas, and were thus significantly different; p < .05 between glioblastomas and anaplastic gliomas, p < .05 between anaplastic gliomas and low-grade gliomas, p < .01 between glioblastomas and low-grade gliomas. The rCBV ratio cutoff value which permitted discrimination between high-grade (glioblastomas and anaplastic gliomas) and low-grade gliomas was 2.60, and the sensitivity and specificity of this value were 100% and 75%, respectively. Conclusion Perfusion MR imaging is a useful and reliable technique for estimating the histologic grade of gliomas.

Polyphenols isolated from Allium cepa L. induces apoptosis by suppressing IAP-1 through inhibiting PI3K/Akt signaling pathways in human leukemic cells.

Allium cepa Linn is commonly used as supplementary folk remedy for cancer therapy. Evidence suggests that Allium extracts have anti-cancer properties. However, the mechanisms of the anti-cancer activity of A. cepa Linn are not fully elucidated in human cancer cells. In this study, we investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in human leukemia cells and their mechanisms. PEAL inhibited cancer cell growth by inducing caspase-dependent apoptosis. The apoptosis was suppressed by caspase 8 and 9 inhibitors. PEAL also up-regulated TNF-related apoptosis-inducing ligand (TRAIL) receptor DR5 and down-regulated survivin and cellular inhibitor of apoptosis 1 (cIAP-1). We confirmed these findings in other leukemic cells (THP-1, K562 cells). In addition, PEAL suppressed Akt activity and the PEAL-induced apoptosis was significantly attenuated in Akt-overexpressing U937 cells. In conclusion, our data suggested that PEAL induced caspase-dependent apoptosis in several human leukemic cells including U937 cells. The apoptosis was triggered through extrinsic pathway by up-regulating DR5 modulating as well as through intrinsic pathway by modulating IAP family members. In addition, PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of leukemia.

Spontaneous Rapid Reduction of a Large Acute Subdural Hematoma

The majority of acute post-traumatic subdural hematomas (ASDH) require urgent surgical evacuation. Spontaneous resolution of ASDH has been reported in some cases. We report here on a case of a patient with a large amount of ASDH that was rapidly reduced. A 61-yr-old man was found unconscious following a high speed motor vehicle accident. On initial examination, his Glasgow Coma Score scale was 4/15. His pupils were fully dilated and non-reactive to bright light. Brain computed tomography (CT) showed a massive right-sided ASDH. The decision was made to treat him conservatively because of his poor clinical condition. Another brain CT approximately 14 hr after the initial scan demonstrated a remarkable reduction of the previous ASDH and there was the new appearance of high density in the subdural space adjacent to the falx and the tentorium. Thirty days after his admission, brain CT revealed chronic SDH and the patient underwent surgery. The patient is currently able to obey simple commands. In conclusion, spontaneous rapid resolution/reduction of ASDH may occur in some patients. The mechanisms are most likely the result of dilution by cerebrospinal fluid and the redistribution of hematoma especially in patients with brain atrophy.

Anaplastic Ganglioglioma in a Middle-aged Woman: A Case Report with a Review of the Literature

We report a case of anaplastic ganglioglioma. A 45-yr-old woman was admitted with a 5-month history of headache and dizziness, both of which progressed slowly. Preoperative magnetic resonance imaging revealed a strong enhancing mass in the left frontal lobe extending to the cingulate gyrus. Adjuvant radiation therapy and chemotherapy were given after gross total resection of the tumor. Histological and immunohistochemical studies showed an anaplastic ganglioglioma. Gangliogliomas of the central nervous system are rather uncommon tumors, and anaplastic ones are extremely rare. The pertinent literature regarding gangliogliomas is reviewed.

Flavonoids from Citrus unshiu Marc. inhibit cancer cell adhesion to endothelial cells by selective inhibition of VCAM-1

Citrus fruits have been used as edible fruit and a component of traditional medicine for various diseases including cancer since ancient times. Herein, we investigated the anticancer activity of flavonoids of Citrus unshiu Marc. (FCM) focusing on anti-metastatic effects. We prepared FCM and performed experiments using MDA-MB-231 human breast cancer cells. FCM inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. FCM inhibited the expression of VCAM-1, but not of ICAM-1, on MDA-MB-231 cells as well as HUVECs. FCM inhibited protein kinase C (PKC) phosphorylation, but not Akt phosphorylation. FCM also inhibited cancer cell invasion in a dose-dependent manner, but not MMP-9 expression. In conclusion, this study suggested that FCM inhibits TNF-induced cancer cell adhesion to HUVECs by inhibiting VCAM-1 through inhibition of PKC, providing evidence that FCM have anti-metastatic activity by inhibiting adhesion molecules and invasion on human breast cancer cells.

Polyphenols from Artemisia annua L Inhibit Adhesion and EMT of Highly Metastatic Breast Cancer Cells MDA‐MB‐231

Recent evidence suggests that polyphenolic compounds from plants have anti‐invasion and anti‐metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti‐metastatic effects of pKAL on the highly metastatic MDA‐MB‐231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial‐mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA‐MB‐231 cells in a dose‐dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA‐MB‐231 cells to ECs through reducing vascular cell adhesion molecule‐1 expression of MDA‐MB‐231 and ECs, but not intracellular adhesion molecule‐1 at the concentrations where pKAL did not influence the cell viability of either MDA‐MB‐231 cells nor EC. Further, pKAL inhibited tumor necrosis factor‐activated MDA‐MB‐231 breast cancer cell invasion through inhibition of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule‐1 and invasion through suppression of EMT. Copyright

Polyphenols Isolated from Allium cepa L. Induces Apoptosis by Induction of p53 and Suppression of Bcl-2 through Inhibiting PI3K/Akt Signaling Pathway in AGS Human Cancer Cells.

Background: The extract of Allium cepa Linn is commonly used as adjuvant food for cancer therapy. We assumed that it includes a potential source of anti-cancer properties. Methods: We investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in AGS human cancer cells. Results: PEAL inhibited cell growth in a dose-dependent manner. It was related to caspase-dependent apoptosis. We confirmed this finding with annexin V staining. PEAL up-regulated p53 expression, and subsequent Bax induction, down regulated Bcl-2 protein, anti-apoptotic protein. In addition, PEAL suppressed Akt activity and PEAL-induced apoptosis were significantly accentuated with Akt inhibitor (LY294002). Conclusions: Our data suggested that PEAL induce caspase-dependent apoptosis through mitochondrial pathway by up-regulating p53 protein, and subsequent Bax protein as well as by modulating Bcl-2 protein, and that PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of cancer.

Flavonoids from Orostachys japonicus A. Berger Inhibit the Invasion of LnCaP Prostate Carcinoma Cells by Inactivating Akt and Modulating Tight Junctions

Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins are frequently over-expressed in cancers and their overexpression is implicated in the invasive potential of cancer. Hence, we investigated the effects of flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ suppressed cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses cancer migration and invasion by tightening TJs through the suppression of claudin expression, and by suppressing MMPs in LnCaP human prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway.

Tetraarsenic hexoxide induces G2/M arrest, apoptosis, and autophagy via PI3K/Akt suppression and p38 MAPK activation in SW620 human colon cancer cells

Tetraarsenic hexoxide (As4O6) has been used in Korean folk medicines for the treatment of cancer, however its anti-cancer mechanisms remain obscured. Here, this study investigated the anti-cancer effect of As4O6 on SW620 human colon cancer cells. As4O6 has showed a dose-dependent inhibition of SW620 cells proliferation. As4O6 significantly increased the sub-G1 and G2/M phase population, and Annexin V-positive cells in a dose-dependent manner. G2/M arrest was concomitant with augment of p21 and reduction in cyclin B1, cell division cycle 2 (cdc 2) expressions. Nuclear condensation, cleaved nuclei and poly (adenosine diphosphate‑ribose) polymerase (PARP) activation were also observed in As4O6-treated SW620 cells. As4O6 induced depolarization of mitochondrial membrane potential (MMP, ΔΨm) but not reactive oxygen species (ROS) generation. Further, As4O6 increased death receptor 5 (DR5), not DR4 and suppressed the B‑cell lymphoma‑2 (Bcl-2) and X-linked inhibitor of apoptosis protein (XIAP) family proteins. As4O6 increased the formation of AVOs (lysosomes and autophagolysosomes) and promoted the conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3)-I to LC3-II in a dose- and time- dependent manner. Interestingly, a specific phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002) augmented the As4O6 induced cell death; whereas p38 mitogen-activated protein kinases (p38 MAPK) inhibitor (SB203580) abrogated the cell death. Thus, the present study provides the first evidence that As4O6 induced G2/M arrest, apoptosis and autophagic cell death through PI3K/Akt and p38 MAPK pathways alteration in SW620 cells.

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.