• 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-$VcR_6$.

• Journal of Hospice and Palliative Care
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• v.14 no.1
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• pp.28-33
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• 2011

Purpose: Recognition of impending death is crucial not only for efficient communication with the caregiver of the patient, but also determination of the time to refer to a separate room. Current studies simply list the events 'that have already occurred' around 48 hours before the death. This study is to analyze the predictability of each event by comparing the time length from 'change' to death. Methods: Subjects included 160 patients who passed away in a palliative care unit in Incheon. The analysis was limited to 80 patients who had medical records for the last week of their lives. We determined 9 symptoms and 8 signs, and established the standard of 'significant change' of each event before death. Results: The most common symptom was increased sleeping (53.8%) and the most common sign was decreased blood pressure (BP) (87.5%). The mean time to death within 48 hours was 46.8% in the case of resting dyspnea, 13.6% in the ease of low oxygen saturation, and 36.9% in the case of decreased BP. The symptom(s) which had the highest positive predictive value (PV) for death within 48 hours was shown to be resting dyspnea (83%), whereas the combination of resting dyspnea and confusion/delirium (65%) had the highest negative PV. As for the most common signs before death within 48 hours, the positive PVs were more than 95%, and the negative PV was the highest when decreased BP and low oxygen saturation were combined. The difference in survival patterns between symptoms and signs was significant. Conclusion: The most reliable symptoms to predict the impending death are resting dyspnea and confusion/delirium, and decline of oxygen saturation and BP are the reliable signs to predict the event.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.289-294
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• 2008

Purpose: To improve the quality of the statistical analysis of papers published in the Journal of the Korean Society for Therapeutic Radiology and Oncology (JKOSTRO) by evaluating commonly encountered errors. Materials and Methods: Papers published in the JKOSTRO from January 2006 to December 2007 were reviewed for methodological and statistical validity using a modified version of Ahn's checklist. A statistician reviewed individual papers and evaluated the list items in the checklist for each paper. To avoid the potential assessment error by the statistician who lacks expertise in the field of radiation oncology; the editorial board of the JKOSTRO reviewed each checklist for individual articles. A frequency analysis of the list items was performed using SAS (version 9.0, SAS Institute, NC, USA) software. Results: A total of 73 papers including 5 case reports and 68 original articles were reviewed. Inferential statistics was used in 46 papers. The most commonly adopted statistical methodology was a survival analysis (58.7%). Only 19% of papers were free of statistical errors. Errors of omission were encountered in 34 (50.0%) papers. Errors of commission were encountered in 35 (51.5%) papers. Twenty-one papers (30.9%) had both errors of omission and commission. Conclusion: A variety of statistical errors were encountered in papers published in the JKOSTRO. The current study suggests that a more thorough review of the statistical analysis is needed for manuscripts submitted in the JKOSTRO.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.57-63
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• 2010

Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.

• Journal of Life Science
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• v.29 no.4
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• pp.410-420
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• 2019

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.