• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.237-243
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• 2016

Oleanolic acid (OA) has a wide variety of bioactivities such as hepatoprotective, anti-inflammatory and anti-cancer activity and is used for medicinal purposes in many Asian countries. In the present study, the effect of OA on induction of autophagy in human hepatocellular carcinoma HepG2 and SMC7721 cells and the related mechanisms were investigated. MTT assay showed that OA significantly inhibited HepG2 and SMC7721 cells growth. OA treatment enhanced formation of autophagic vacuoles as revealed by monodansylcadaverine (MDC) staining. At the same time, increasing punctuate distribution of microtubule-associated protein 1 light chain 3 (LC3) and an increasing ratio of LC3-II to LC3-I were also triggered by OA incubation. In addition, OA-induced cell death was significantly inhibited by autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) pretreatment. And we found out that OA can suppress the PI3K/Akt1/mTOR signaling pathway. Furthermore, our data suggested that OA-triggered autophagy was ROS-dependent as demonstrated by elevated cellular ROS levels by OA treatment. When ROS was cleared by N-acetylcysteine (NAC), OA-induced LC3-II convertsion and cell death were all reversed. Taken together, our results suggest that OA exerts anticancer effect via autophagic cell death in hepatocellular carcinoma.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.251-256
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• 2009

Previous observations suggest that Bis, a Bcl-2-binding protein, may playa role the neuronal and glial differentiation in vivo. To examine this further, we investigated Bis expression during the in vitro differentiation of P19 embryonic carcinoma cells induced by retinoic acid (RA). Western blotting and RT-PCR assays showed that Bis expression was temporarily decreased during the free floating stage and then began to increase on day 6 after the induction of differentiation. Double immunostaining indicated that Bis-expressing cells do not express several markers of differentiation, including NeuN, MAP-2 and Tuj-1. However, some of the Bis-expressing cells also were stained with GFAP-antibodies, indicating that Bis is involved glial differentiation. Using an shRNA strategy, we developed bis-knock down P19 cells and compared them with control P19 cells for the expression of NeuroD, Mash-1 and GFAP during RA-induced differentiation. Among these, only GFAP induction was significantly attenuated in Pl9-dnbis cells and the population showing GFAP immunoreactivity was also decreased. It is noteworthy that distribution of mature neurons and migrating neurons was disorganized, and the close association of migrating neuroblasts with astrocytes was not observed in P19-dnbis cells. These results suggest that Bis is involved in the migration-inducing activity of glial cells.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.2
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• pp.92-95
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• 2014

Objective: This study sought to evaluate platelet volume indices (mean platelet volume [MPV], platelet distribution width [PDW], and platelet large cell ratio [P-LCR]) in varicocele patients, and compare it with platelet volume parameters in healthy controls. Methods: This cross-sectional study involved 2 groups: group 1 included 51 varicocele subjects and group 2 consisted of 50 healthy control subjects of similar ages. Peripheral venous blood samples were collected with ethylenediaminetetraacetic acid-K2 anticoagulant between 8:30 AM and 10 AM following an overnight fast. Platelet volume parameters (MPV, PDW, and P-LCR) were measured in both groups within 2 hours of sampling. Results: The mean PDW, MPV, and P-LCR were $13.9{\pm}2.5%$, $10.1{\pm}1.3fL$, and $27.3{\pm}7.8%$ in varicocele patients, respectively, and were $12.6{\pm}2.4%$, $9.3{\pm}1.1fL$, and $21.9{\pm}6.4%$ in the control group, respectively. The mean PDW, MPV, and P-LCR were significantly higher in the varicocele group than the control group. Conclusion: The results of the present study suggest that vascular components may play an important role in the pathophysiology of varicocele; therefore, there is a great need for prospective studies to confirm this relationship.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.5
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• pp.265-270
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• 2016

Objectives: To gain information on anatomical variation in anterolateral thigh (ALT) flaps in a series of clinical cases, with special focus on perforators and pedicles, for potential use in reconstruction of oral and maxillofacial soft tissue defects. Materials and Methods: Eight patients who underwent microvascular reconstructive surgery with ALT free flaps after ablative surgery for oral cancer were included. The number of perforators included in cutaneous flaps, location of perforators (septocutaneous or musculocutaneous), and the course of vascular pedicles were intraoperatively investigated. Results: Four cases with a single perforator and four cases with multiple perforators were included in the ALT flap designed along the line from anterior superior iliac spine to patella. Three cases had perforators running the septum between the vastus lateralis and rectus femoris muscle (septocutaneous type), and five cases had perforators running in the vastus lateralis muscle (musculocutaneous type). Regarding the course of vascular pedicles, five cases were derived from the descending branch of the lateral circumflex femoral artery (type I), and three cases were from the transverse branch (type II). Conclusion: Anatomical variation affecting the distribution of perforators and the course of pedicles might prevent use of an ALT free flap in various reconstruction cases. However, these issues can be overcome with an understanding of anatomical variation and meticulous surgical dissection. ALT free flaps are considered reliable options for reconstruction of soft tissue defects of the oral and maxillofacial area.

• Progress in Medical Physics
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• v.7 no.2
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• pp.57-65
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• 1996

Total Skin Electron Beam Therapy (TSEBT) is one of the most effective treatment methods for superficially disseminated skin cancer or cutaneous T-cell lymphoma. We have treated a patient with cutaneous T-cell lymphoma. We have used Stanford technique using six dual field. The nominal energy of electron beam was 4MeV. SSD was 390cm and the gantry angles of dual fields were 76$^{\circ}$ and 104$^{\circ}$. The dose profiles of single field and dual fields were measured with films and a Farmer type ion chamber. The field uniformity was 10％ over the patient's surface. During treatment, the patient was placed in six different positions for homogenous dose distribution over the body surface. The areas not directly exposed to the path of the electron beam (soles of feet, perineum and vertex of scalp) were boosted with 7MeV electron beam. During the treatment, lens, fingernails and toenails were shielded.

• Progress in Medical Physics
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• v.25 no.1
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• pp.23-30
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• 2014

The purpose of this study is to evaluate the developed dose verification program for in vivo dosimetry based on transit dose in radiotherapy. Five intensity modulated radiotherapy (IMRT) plans of lung cancer patients were used in the irradiation of a homogeneous solid water phantom and anthropomorphic phantom. Transit dose distribution was measured using electronic portal imaging device (EPID) and used for the calculation of in vivo dose in patient. The average passing rate compared with treatment planning system based on a gamma index with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit was 95% for the in vivo dose with the homogeneous phantom, but was reduced to 81.8% for the in vivo dose with the anthropomorphic phantom. This feasibility study suggested that transit dose-based in vivo dosimetry can provide information about the actual dose delivery to patients in the treatment room.

• The Korean Journal of Nuclear Medicine
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• v.36 no.1
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• pp.74-79
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• 2002

In addition to the well-established use of positron emission tomography (PET) in clinical oncology, novel roles for PET are rapidly emerging in the field of gene therapy. Methods for controlled gene delivery to living bodies, made available through advances in molecular biology, are currently being employed in animals for research purposes and in humans to treat diseases such as cancer. Although gene therapy is still in its early developmental stage, it is perceived that many serious illnesses could be treated successfully by the use of therapeutic gene delivery. A major challenge for the widespread use of human gene therapy is to achieve a controlled and effective delivery of foreign genes to target cells and subsequently, adequate levels of expression. As such, the availability of noninvasive imaging methods to accurately assess the location, duration, and level of transgene expression is critical for optimizing gene therapy strategies. Current endeavors to achieve this goal include methods that utilize magnetic resonance imaging, optical imaging, and nuclear imaging techniques. As for PET, reporter systems that utilize genes encoding enzymes that accumulate positron labeled substrates and those transcribing surface receptors that bind specific positron labeled ligands have been successfully developed. More recent advances in this area include improved reporter gene constructs and radiotracers, introduction of potential strategies to monitor endogenous gene expression, and human pilot studies evaluating the distribution and safety of reporter PET tracers. The remarkably rapid progress occurring in gene imaging technology indicates its importance and wide range of application. As such, gene imaging is likely to become a major and exciting new area for future application of PET technology.

• Journal of IKEEE
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• v.11 no.4
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• pp.257-264
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• 2007

The MM22 microtron has used as a cancer therapy machine from Nov. 1986 to Feb. 2006. This machine was moved and installed to a radiation research center to use as an education and research tool from treatment machine because of aging of MM22 microtron. In this paper, for extracting the electron beam from microtron, operation principle of the microtron, system characteristics of each module, and pulse structures were reviewed. The beam extraction and measurement were performed after measuring pulses of each major module and extraction trials in the beam line. After finishing the movement of MM22 microtron, the 30mA target current in the case of 10 MV X-ray beam was extracted and the beam flatness of radiation distribution was acquired within 3% error ratio after 100 MU was irradiated on X-omatV Film at SSD 100 cm and field size $10{\times}10cm^2$. As a result, the microtron movement and new installation was performed with success.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.1-13
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• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.1-9
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• 2006

Human solid tumors exhibit a multicellular resistance (MCR) resulting from limited drug penetration and decreased sensitivity of tumor cells when interacting with their microenvironments. Multicellular cultures represent solid tumor condition in vivo and provide clinically relevant data. There is little data on antitumor effect of paclitaxel (PTX) in multicellular cultures although its MCR has been demonstrated. In the present study, we evaluated antiproliferative effects of PTX in multicellular layers (MCL) of DLD-1 human colorectal carcinoma cells. BrdU labeling index (LI), thickness of MCL, cell cycle distribution and cellular uptake of calcein were measured before and after exposure to PTX at 0.1 to 50 ${\mu}M$ for 24, 48 and 72 hrs. BrdU LI and thickness of MCL showed a concentration- and time-dependent decrease and the changes in both parameters were similar, i.e., 34.2% and 40.6% decrease in BrdU LI and thickness, respectively, when exposed to $50\;{\mu}M$ for 72 hr. The DLD-1 cells grown in MCL showed increase in $%G_{0}/G_{1}$ and resistance to cell cycle arrest and apoptosis compared to monolayers. Calcein uptake in MCL did not change upon PTX exposure, indicating technical problems in multicellular system. Overall, these data indicate that antitumor activity of PTX may be limited in human solid tumors (a multicellular system) and MCL may be an appropriate model to study further pharmacodynamics of PTX.