• Journal of Life Science
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• v.19 no.8
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• pp.1073-1080
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• 2009

A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

• Journal of Life Science
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• v.26 no.2
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• pp.147-154
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• 2016

Osteosarcoma (OS) is the most common and malignant bone tumors. Although many types of resection surgery and experimental agents were developed, median survival and clinical prognosis are poorly investigated. Recently, several researches have reported that Eucheuma cottonii has potent as protective effects of coal dust-induced lung damage via inhibition of malondialdehyde (MDA) and oxidative stress in bronchoalveolar lavage fluids (BALF). However, anti-cancer effects and specific molecular mechanism of extract from Eucheuma cottonii (EE) has not been clearly studied yet. This study evaluated that anti-cancer potential of EE in human osteosarcoma Saos-2 cells. EE indicated cytotoxicity on Saos-2 cells in a dose-dependent manner. Morphological degradation and nucleic condensation were also observed under the EE treatment. However, it did not significantly affect on non-cancerous kidney HEK-293 cells under the same concentration which is shown cytotoxicity on Saos-2 cells. The phosphorylation of Fas-Associated Death Domain (FADD) and expression of cleaved caspase-8, -7 and -3 were upregulated in a dose-dependent manner. In immunofluorescence staining, expression level of Fas and cleaved PARP were upregulated by EE treatment. Furthermore, treatment of EE induces upregulation of sub G1 phase by flow cytometry analysis. The results demonstrated that EE has a therapeutic potential against osteosarcoma via FADD mediated caspase cascade apoptosis signal pathway.

• The Journal of Korean Society for Radiation Therapy
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• v.28 no.2
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• pp.171-178
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• 2016

Purpose : In order to minimize the dose of femoral head as an appropriate treatment plan for rectal cancer radiation therapy, we compare and evaluate the usefulness of 3-field 3D conformal radiation therapy(below 3fCRT), which is a universal treatment method, and 5-field 3D conformal radiation therapy(below 5fCRT), and Volumetric Modulated Arc Therapy (VMAT). Materials and Methods : The 10 cases of rectal cancer that treated with 21EX were enrolled. Those cases were planned by Eclipse(Ver. 10.0.42, Varian, USA), PRO3(Progressive Resolution Optimizer 10.0.28) and AAA(Anisotropic Analytic Algorithm Ver. 10.0.28). 3fCRT and 5fCRT plan has $0^{\circ}$, $270^{\circ}$, $90^{\circ}$ and $0^{\circ}$, $95^{\circ}$, $45^{\circ}$, $315^{\circ}$, $265^{\circ}$ gantry angle, respectively. VMAT plan parameters consisted of 15MV coplanar $360^{\circ}$ 1 arac. Treatment prescription was employed delivering 54Gy to recum in 30 fractions. To minimize the dose difference that shows up randomly on optimizing, VMAT plans were optimized and calculated twice, and normalized to the target V100%=95%. The indexes of evaluation are D of Both femoral head and aceta fossa, total MU, H.I.(Homogeneity index) and C.I.(Conformity index) of the PTV. All VMAT plans were verified by gamma test with portal dosimetry using EPID. Results : D of Rt. femoral head was 53.08 Gy, 50.27 Gy, and 30.92 Gy, respectively, in the order of 3fCRT, 5fCRT, and VMAT treatment plan. Likewise, Lt. Femoral head showed average 53.68 Gy, 51.01 Gy and 29.23 Gy in the same order. D of Rt. aceta fossa was 54.86 Gy, 52.40 Gy, 30.37 Gy, respectively, in the order of 3fCRT, 5fCRT, and VMAT treatment plan. Likewise, Lt. Femoral head showed average 53.68 Gy, 51.01 Gy and 29.23 Gy in the same order. The maximum dose of both femoral head and aceta fossa was higher in the order of 3fCRT, 5fCRT, and VMAT treatment plan. C.I. showed the lowest VMAT treatment plan with an average of 1.64, 1.48, and 0.99 in the order of 3fCRT, 5fCRT, and VMAT treatment plan. There was no significant difference on H.I. of the PTV among three plans. Total MU showed that the VMAT treatment plan used 124.4MU and 299MU more than the 3fCRT and 5fCRT treatment plan, respectively. IMRT verification gamma test results for the VMAT plan passed over 90.0% at 2mm/2%. Conclusion : In rectal cancer treatment, the VMAT plan was shown to be advantageous in most of the evaluation indexes compared to the 3D plan, and the dose of the femoral head was greatly reduced. However, because of practical limitations there may be a case where it is difficult to select a VMAT treatment plan. 5fCRT has the advantage of reducing the dose of the femoral head as compared to the existing 3fCRT, without regard to additional problems. Therefore, not only would it extend survival time but the quality of life in general, if hospitals improved radiation therapy efficiency by selecting the treatment plan in accordance with the hospital's situation.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.99-106
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• 1998

Purpose : We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Materials and Methods : Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and subrethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using $Sperman-H\"{a}rbor$ method and mathematical analysis of survival curves was done with linear-quadratic (LQ) , multitarget-single hit(MS) model and mean inactivation dose$(\v{D})$. Results : Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85 The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of $\alpha$ for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of $\beta$ were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79. MKN-45, HeLa and PC-14 were 1.59. 1.84. 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1 69 respectively. The $\v{D}s$ calculated by Gauss-Laguerre method were 1.62, 2.37, 2,01 and 3.95 respectively So the SF2 was significantly correlated with $\alpha$, Do and $\v{D}$. Their Pearson correlation coefficiencics were -0.953 and 0,993. 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, ${\alpha}$, ${\beta}$, Do, $\v{D}$. Conclusion : The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-l4 was the least sensitive. SF2 was well correlated with ${\alpha}$, Do, and $\v{D}$. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.170-180
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• 2008

Purpose : Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods : Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results : The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/Bcl-2 expression in geneticin-treated animal model. Conclusion : Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain.

• Journal of Hospice and Palliative Care
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• v.1 no.1
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• pp.39-46
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• 1998

Purpose : Hospice Care is considered as one of the most perfect solutions for the problems brought up as the number of chronically ill patients are increasing rapidly and most of social welfare oriented countries are seeking the quality of life. Our former studies(1996, 1997) were to find out the current status of the hospice care in Korea by surveying terminally ill patients and their family members as well as medical professionals. The former study was also to conduct the operation research by developing an information service system for training of hospice care teams and volunteers, and hospice patients management. The purpose of this study was that hospice information service system was tested by home visiting hospice care through visiting nurses. Methods : From October 1, 1997 to March 31, 1998, Twenty six terminal cancer patients were included in this study from Seoul National University Hospital and other hospital. Databases and homepage, hospice information service system were designed and developed for the information needed for the hospice care before this study by our research team and this services were available through the internet. Visiting nurses were trained about this system and they visited the patients with PC notebook and provided them hospice care with hospice information system. They collected physical, psychiatric, social data of the subjects at the first visit and during hospice care at home. Results : Sixteen subjects(61.5%) died during the study and the mean survival was 20.7 days. Anorexia(96.2%), immobility(88.5%) and pain(84.6%) were the major symptom in the 26 subjects, Altered nutrition(26.1%) and pain(12.4%) were the most frequent diagnoses in 226 nursing diagnoses of the subjects. Families understood and demanded the hospice care more than patients. And most patients and families didn't demand spiritual or social care. Conclusion : Through this demonstration study, it was found that we have to provide the information of pain management and nutritional support for patients by the nurses and visiting hospice nurse. The information service system needs to be upgraded with information and manpower of spiritual and social care according to the findings.

• The Korean Society of Law and Medicine
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• v.20 no.3
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• pp.83-139
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• 2019

Recognition of liability for damages due to medical malpractice has been developed largely on the basis of two paths. First is the case where there is an error in a physician's medical practice and this infringes upon the legal interests of life and body, and the compensation for monetary and non-monetary damages incurred from such infringement on life and body becomes an issue. Second is the case where there is a breach of a physician's duty of explanation that results in a infringement on the patient's right of autonomous decision, and the compensation for non-monetary damages incurred from such infringement becomes an issue. However, even if there is a medical error, since it is difficult to prove the causation between the medical error of a physician and the infringement upon legal interests, the physician's responsibility for damage compensation is denied in some cases. Consider, for example, a case where a patient is already in the final stage of cancer and has a very low possibility of a complete recovery even if proper treatment is received from the physician. Here, it is not appropriate to refuse recognition of any damage compensation based on the reason that the possibility of the patient dying is very high even in the absence of a medical error. This is so because, at minimum, non-monetary damage such as psychological suffering is incurred due to the physician's medical error. In such a case, our courts recognize on an exceptional basis consolation money compensation for losing the chance to receive proper treatment. However, since the theoretical system has not been established in minutiae, what comes under the benefit and protection of the law is not clearly explicated. The recent discourse on compensating for damages incurred by patients, even when the causation between the physician's medical error and infringement upon the legal interests of life and body is denied, by establishing a new legal interest is based on the "legal principle of loss of opportunity for treatment." On what should be the substance of the new legal interest, treatment possibility argument, expectation infringement argument, considerable degree of survival possibility infringement argument and loss of opportunity for treatment argument are being put forth. It is reasonable to see the substance of this protected legal interest as "the benefit of receiving treatment appropriate to the medical standard" according to the loss of opportunity for treatment argument. The above benefit to the patient is a value inherent to human dignity that should not be infringed upon or obstructed by anyone, and at the same time, it is a basic desire regarding life and a benefit worthy of protection by law. In this regard, "the benefit of receiving treatment appropriate to the medical standard" can be made concrete as one of the general personal rights related to psychological legal interest.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.1
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• pp.52-58
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• 2016

Purpose Recent retrospective studies are being actively conducted to analyze the survival of patients with SUVmax, MTV, TLG, such as information from a variety of PET originating. However, there is no clear way is difficult to accurately measure the volume of the tumor may be the difference between the caster is raised. In this study, to evaluate compare the volume measuring methods according to the characteristics of the tumor. Materials and Methods 18F-saline to fill the NEMA IEC Body Phantom insert the volume of balance and imbalance in phantom were acquired to the Biograph truepoint 40 (Siemens medical system, Germany) PET/CT scanner. The ratio of the volume and Background was acquired as 3.0, 5.0, 8.0, 18, 40. Clinical patients were randomly selected 120 people in staging patients with cancer of the digestive system from the year 2010 until the year 2014. Measurement methods were used a 40% threshold, 50% threshold and gradient segmentation technique, i.e. PET EDGE. Five years of experience of the two radio-technologist and one doctor was measured by repeated three times. Analysis methods were Intraclass correlation coefficient and Pearson correlation. Results In Phantoms, the 40% threshold method gave the best concordance between measured and actual volumes (r = 0.992, 0.997). In clinical patient outcome agreement between observers EDGE it is as high as 0.999 (CI: 0.998-0.999). And there were no statistical significance of the difference between the measurements (P = 0.620). 40% threshold method showed the best correlation between the measurements (r = 0.953). Increasing the ratio of tumor to background decreased the influence of a measuring method. Conclusion How to measure volume of the tumor in the patient was clinically most useful is 50% and the lowest impact on the characteristics of the tumor. Therefore, to reduce the background of the patients in PET/CT scan, it should be required research and effort.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.432-444
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• 1993

Multidrug resistance(MDR) phenotype is frequently observed in animal and human cancer cell lines selected for in vitro resistance to a single chemotherapeutic agent. It is characterized by the diminished drug accumulation and is related to the drug efflux mechanism in resistant cells. In the present study, adriamycin resistant cells(L1210-$AdR_6$ : $10^{-6}M$ adriamycin, $-AdR_5$ : $10^{-5}M$) and vincristine resistant cells (L1210-$VcR_7$ : $10^{-7}M$ vincristine, $-VcR_6$ : $10^{-6}M$) were produced from mouse lymphoblastic leukemia cell line L1210. Growth profiles of survived cells were observed for 5 days with MTT(thiazolyl blue) assay and resistance was compared with $IC_{50}$(drug concentration of 50% survival reduction in absorbance). Resistant cells proliferated more slowly than sensitive cell. Doubling times were 29.7hr in L1210, 68.7hr in L1210-$AdR_5$ and 58.2hr in $-VcR_6$. MDRs expressed as resistance factor were as follows, L1210-$AdR_5$ was 76.4 times for vincristine, L1210-$VcR_6$ was 96.4 times for adriamycin. The cell membrane proteins with three different M.W. were recognized to be related resistance, 220, 158, and 88 kd in L1210-$AdR_5$, 158, 140 and 88 kd in L1210-$VcR_6$ by SDS-PAG electrophoresis. Cell surface membrane proteins were identified by radio-iodination and autoradiogram, their molecular weights were 158, 72.8, and 42.4 Kd in L1210-$VcR_6$.