• IMMUNE NETWORK
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• v.9 no.6
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• pp.236-242
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• 2009

Background: Melanoma is the most fatal form of skin cancer due to its rapid metastasis. Recently, several studies reported that selenium can induce apoptosis in melanoma cells. However, the precise mechanism remains to be elucidated. In this study, we investigated the effect of selenium on cell proliferation in murine melanoma and on tumor growth and metastasis in C57BL/6 mice. Methods: Cell proliferation was measured by MTT assay in selenium-treated melanoma cells. Cell cycle distribution was analysized by staining DNA with propidum iodide (PI). mRNA and protein expression related to cell cycle arrest was measured by reverse transcription PCR and western blot. Tumor growth and metastasis was measured by in vivo model. Results: Selenium was suppressed the proliferation of melanoma cells in a dose dependent manner. The growth inhibition of melanoma by selenium was associated with an arrest of cell cycle distribution at G0/G1 stage. The mRNA and protein level of CDK2/CDK4 was suppressed by treatment with selenium in a time-dependent manner. In vivo, tumor growth was not suppressed by selenium; however tumor metastasis was suppressed by selenium in mouse model. Conclusion: These results suggest that selenium might be a potent agent to inhibit proliferative activity of melanoma cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.463-467
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• 2012

Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 $mg/m^2$ on days one and eight intravenously over 90 minutes, followed by docetaxel 75 $mg/m^2$ on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8371-8376
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• 2014

Background: The use of statistical methods has become an imperative tool in breast cancer survival data analysis. The purpose of this study was to develop the best statistical probability model using the Bayesian method to predict future survival times for the black non-Hispanic female breast cancer patients diagnosed during 1973-2009 in the U.S. Materials and Methods: We used a stratified random sample of black non-Hispanic female breast cancer patient data from the Surveillance Epidemiology and End Results (SEER) database. Survival analysis was performed using Kaplan-Meier and Cox proportional regression methods. Four advanced types of statistical models, Exponentiated Exponential (EE), Beta Generalized Exponential (BGE), Exponentiated Weibull (EW), and Beta Inverse Weibull (BIW) were utilized for data analysis. The statistical model building criteria, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) were used to measure the goodness of fit tests. Furthermore, we used the Bayesian approach to obtain the predictive survival inferences from the best-fit data based on the exponentiated Weibull model. Results: We identified the highest number of black non-Hispanic female breast cancer patients in Michigan and the lowest in Hawaii. The mean (SD), of age at diagnosis (years) was 58.3 (14.43). The mean (SD), of survival time (months) for black non-Hispanic females was 66.8 (30.20). Non-Hispanic blacks had a significantly increased risk of death compared to Black Hispanics (Hazard ratio: 1.96, 95%CI: 1.51-2.54). Compared to other statistical probability models, we found that the exponentiated Weibull model better fits for the survival times. By making use of the Bayesian method predictive inferences for future survival times were obtained. Conclusions: These findings will be of great significance in determining appropriate treatment plans and health-care cost allocation. Furthermore, the same approach should contribute to build future predictive models for any health related diseases.

• Journal of Life Science
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• v.26 no.4
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• pp.398-405
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• 2016

Statins, the inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used in treatments of hypercholesterolemia and newly known as anti-cancer effect of various cancer cells. Recently, several studies suggested that reactive oxygen species (ROS) play a critical role on cell death signaling. However, mechanism of ROS by rosuvastatin is currently unclear. This study aimed to explore the molecular mechanism of apoptosis by rosuvastatin in human prostate cancer PC-3 cells. Cell viability and apoptosis-related protein expression were measured by MTT assay and western blotting, respectively. In addition, the levels of apoptosis and ROS were analyzed. The results showed that rosuvastatin dramatically reduced cell viability in a dose- and time-dependent manner. We confirmed that rosuvastatin induced apoptosis through reduction of procaspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) in PC-3 cells. In addition, rosuvastatin stimulated ROS production in a dose-dependent manner and pre-treatment with N-acetylcysteine (NAC), a ROS scavenger, significantly recovered rosuvastatin-induced ROS and apoptosis. Thus, we concluded that rosuvastain induces apoptosis through generation of ROS in human prostate cancer PC-3 cells and provides a promising approach to improve the efficacy of cancer therapy.

• Journal of Korean Academy of Nursing Administration
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• v.7 no.3
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• pp.403-414
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• 2001

The study was intended to identify the nurses' experiences, understanding, and attitudes on DNR. Also, the study was to provide the data base for a standard of DNR decision-making and practice. The sample consisted of 347 nurses in eight general hospitals. The data were collected between August 1 and August 31, 2000. The data were analyzed using descriptive statistics and $x^2-test$. The results of the study were as follows : 1. Regarding DNR-related experience, 74.6 percent of the participants experienced DNR situations. Eleven percent of the participants received DNR education. DNR was most frequently (81.5%) requested by family members and relatives of patients. The decision-making on DNR was most frequently (76.8%) made by agreement between family members and medical staff. The DNR order was recorded at 81.9 percent on charts. Problems after DNR order were negligence in treatment and nursing care (30.6%) and guilty feelings due to doing the best (22.1%). CPR (cardiopulmonary resuscitation) was performed about 49.8 percent of DNR cases. 2. Regarding understanding and attitude on DNR, most of the participants (93.1%) thought DNR was necessary. The major reasons for the necessity of DNR were impossible recovery (44.4%) and death with dignity (41.1%). The decision-making on DNR was most frequently made by patient and family members (47.8%) and followed by agreement between family members and medical staff (25.6%), and patients themselves (16.4%). Most of the participants thought that medical staff must explain DNR to critical and end-of-life patients and their family members. Forty four percent of the participants thought that the most appropriate time for DNR explanation was when patients with critical disease were admitted to hospitals. Most of the participants (90.2%) thought a guide book for DNR is necessary to be made in hospitals. 3. There were significant differences in the participants' understanding and attitudes on DNR according to religion career education and experience of DNR. Of the participants those who have religions and education experience on DNR thought that there would be more DNR requests after DNR is explained to patients and family members (p<.05). In addition, there was higher understanding on the necessity of DNR in those who have more career and DNR experience(p<.01). The findings of the study suggest that a guide book for DNR need to be made with inclusion of legal, ethical, and cultural aspects. Also, there needs to be more education on DNR in medical ethics to health care professional and to provide more information on DNR to the general public.

• Molecules and Cells
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• v.25 no.1
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• pp.55-63
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• 2008

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective death of motor neurons. Mutations in the SOD1 gene are responsible for a familial form of ALS (FALS). Although many studies suggest that mutant SOD1 proteins are cytotoxic, the mechanism is not fully understood. To investigate the role of mutant SOD1 in FALS, human SOD1 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD fusion proteins (wild type and mutants). The expressed and purified PEP-1-SOD fusion proteins were efficiently transduced into neuronal cells. Neurones harboring the A4V, G93A, G85R, and D90A mutants of PEP-1-SOD were more vulnerable to oxidative stress induced by paraquat than those harboring wild-type proteins. Moreover, neurones harboring the mutant SOD proteins had lower heat shock protein (Hsp) expression levels than those harboring wild-type SOD. The effects of the transduced SOD1 fusion proteins may provide an explanation for the association of SOD1 with FALS, and Hsps could be candidate agents for the treatment of ALS.

• Toxicological Research
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• v.29 no.2
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• pp.91-98
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• 2013

Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower ($2.73{\pm}0.32{\mu}g/ml$; p<0.01) than the content in the extract that contained the endocarps ($28.50{\pm}6.71{\mu}g/ml$); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

• Journal of Chest Surgery
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• v.20 no.1
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• pp.112-127
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• 1987

Myasthenia gravis is a neuromuscular transmission function disorder characterized by fatigue and weakness of voluntary muscles. This muscular weakness is intensified by activity and stress, and improved by the use of anticholinesterase compounds. It was initially described by Erb in 1879 and later named myasthenia gravis by Jolly in 1895. Although the pathogenesis is Known to be an autoimmune related reduction in the number of available acetylcholine receptors at neuromuscular junctions, the role of thymus in myasthenia gravis is still unclear and under investigation. Thymectomy in the management of myasthenia gravis has become increasingly important since Dr. Blalock observed in 1939 that some patients with thymic tumors and myasthenia gravis improved following thymectomy. A clinical study of 102 cases of myasthenia gravis was performed at Yonsei University College of Medicine. Seoul, Korea from Jan. 1976 to Jun. 1986. In order to determine which factors are of prognostic significance, attention is focused upon pre-operative patient evaluation, problems in operative and post-operative care, and long-term follow-up observations. The results were as follows: 1. The sex distribution was 67 females and 35 males, the mean age of onset was 28.95*1.69 years, and the maximal incidence occurred between 21 and 40 years of age [56 cases: 54.9%]. 2. Clinical manifestations of ocular symptoms were seen to 70 patients [68.6%] extremities weakness in 33 [32.3%], bulbar weakness in 29 [28.4%], and dyspnea in 13 [12.7%]. 3. Study cases more than two thirds were classified as mild types [MG 1 and MG 11A] and 6 cases as grave [MG 1V] based on the modified Osserman`s classification system, 4. Thymectomy was performed in 19 cases which presented in severe myasthenia symptoms and showed no improvement with cholinergic drugs. Histologic examination of the excised thymus glands revealed no abnormalities in 4 cases, thymic hyperplasia in 5, benign thymoma in 5, and malignant thymoma in 5. 5. Immediate post-operative complications included 2 cases of pneumothorax which were treated by tube thoracostomies, there was no operative mortality. 6. The response to cholinergic drugs in 36 cases younger than 20 years old and in 27 cases older than 40 years was relatively poor, while that in 35 cases between the ages of 21 and 40 years old was good. 7. Thirty of 39 cases in groups IIB, III & IV improved markedly with medical or surgical management while only 16 of 59 cases in the mild groups [I and IIA] improved, almost all surgical cases improved in all categories. 8. There were 5 deaths. occurring between 7 months and 3 years 3 months of treatment of myasthenia gravis. The causes of death were myasthenic crisis in 2 cases, respiratory failure due to candidiasis & radiation pneumonitis in one case, cerebral hemorrhage due to high blood pressure in two case.

• Journal of Chest Surgery
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• v.32 no.8
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• pp.702-708
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• 1999

Background: Surgical closure of the PDA in premature infants with complications or contraindications to indomethacin use, or recurrence of symptomatic PDA is a safe and effective procedure with low operative risk and minimal complications. Material and Method: From April 1996 to August 1998, 11 premature infants with body weight under 1.5 kg at operation underwent operation for a symptomatic PDA (male:5, female: 6). Associated dise ases were congenital heart disease(7), hyaline membrane disease(6), intraventricular hemor rhage(4), pneumonia(4), pneumothorax(3), hyperbilirubinemia(2), necrotizing enterocolitis(2), renal failure(1), epilepsy(1), and hydrocephalus(1). Surgical techniques are hemoclipping(8) and ligation(3). The size of PDA was 3~6 mm (5.0$\pm$1.2). Result: Systolic and diastolic blood pressure rised and heart rates decreased after PDA closure. ABGA improved postoperatively. There were no surgical complications. Six infants with improved ABGA data were weaned from mechanical ventilatory support. The follow-up durations after discharge were 3 month to 12 month. Five deaths were not related to operation. The causes of death were hyaline membrane disease(2), bronchopulmonary dysplasia with pneumonia(1), sepsis(1), and con gestive heart failure with respiratory distress syndrome(1). Conclusion: Early operative closure is the treatment of choice in most premature infants with a hemodynamically significant shunt(PDA), recurrence of symptomatic PDA, complications of Indomethacin, or contraindi cations to Indomethacin.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10193-10198
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• 2015

Background: Cancer is a major cause of mortality in developing countries and correct and valid information about the epidemiology of this disease is the first step in the planning of health care in each region. The aim of this study was to determine the relative frequency, mean age and sex ratio of the most 10 common non-skin cancers in the world and Iran, among patients referred to an oncology clinic. Materials and Methods: This descriptive study was conducted in Mashhad, north east of Iran. The data obtained from the records of patients referred to the private oncology center between the years of 1985-2012". According to the latest report of GLOBOCAN study commonest malignancies included were lung, breast, colorectal, prostate, stomach, liver, cervix, esophageal, bladder cancers and Non-Hodgkin lymphoma. Results: A total of 4,606 cases were analyzed. The mean age was $55.5{\pm}13.8years$ (male: $59.5{\pm}13.9$, female: $52.6{\pm}12.9$). Overall, breast cancer (1,264 cases, relative frequency of 27.4%) was the most prevalent cancer; however the mean ages of diagnosis were not significantly different between 5-year time period divisions (p=0.290). The most common cancer in men was esophageal cancer (26.3%).The lowest mean age was related to women diagnosed with breast cancer ($48.5{\pm}11.8$) and men with non-Hodgkins lymphoma ($48.4{\pm}17.8$). There were statistically significant differences between the mean age of men and women with gastric (p=0.003) and esophageal cancers (p<0.001). Male to female sex ratios in our study for bladder, lung and stomach cancers were 6.57, 2.60 and 2.50 respectively. Conclusions: The results showed that breast cancer tends to be found in younger female patients and bladder cancer appears more often in men. Screening in target population in addition to early diagnosis may reduce death and disability.