P70S6K and Elf4E Dual Inhibition Is Essential to Control Bladder Tumor Growth and Progression in Orthotopic Mouse Non-muscle Invasive Bladder Tumor Model

We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 microM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.

P70S6K and Elf4E Dual Inhibition Is Essential to Control Bladder Tumor Growth and Progression in Orthotopic Mouse Non-muscle Invasive Bladder Tumor Model

We investigated how the dual inhibition of the molecular mechanism of the mammalian target of the rapamycin (mTOR) downstreams, P70S6 kinase (P70S6K) and eukaryotic initiation factor 4E (eIF4E), can lead to a suppression of the proliferation and progression of urothelial carcinoma (UC) in an orthotopic mouse non-muscle invasive bladder tumor (NMIBT) model. A KU-7-luc cell intravesically instilled orthotopic mouse NMIBC model was monitored using bioluminescence imaging (BLI) in vivo by interfering with different molecular components using rapamycin and siRNA technology. We then analyzed the effects on molecular activation status, cell growth, proliferation, and progression. A high concentration of rapamycin (10 microM) blocked both P70S6K and elF4E phosphorylation and inhibited cell proliferation in the KU-7-luc cells. It also reduced cell viability and proliferation more than the transfection of siRNA against p70S6K or elF4E. The groups with dual p70S6K and elF4E siRNA, and rapamycin reduced tumor volume and lamina propria invasion more than the groups with p70S6K or elF4E siRNA instillation, although all groups reduced photon density compared to the control. These findings suggest that both the mTOR pathway downstream of eIF4E and p70S6K can be successfully inhibited by high dose rapamycin only, and p70S6K and Elf4E dual inhibition is essential to control bladder tumor growth and progression.

Establishment of an Orthotopic Mouse Non-Muscle Invasive Bladder Cancer Model Expressing the Mammalian Target of Rapamycin Signaling Pathway

We established an orthotopic non-muscle invasive bladder cancer (NMIBC) mouse model expressing the mammalian target of the rapamycin (mTOR) signaling pathway. After intravesical instillation of KU-7-lucs (day 0), animals were subsequently monitored by bioluminescence imaging (BLI) on days 4, 7, 14, and 21, and performed histopathological examination. We also validated the orthotopic mouse model expressing the mTOR signaling pathway immunohistochemically. In vitro BLI photon density was correlated with KU-7-luc cell number (r2 = 0.97, P < 0.01) and in vivo BLI photon densities increased steadily with time after intravesical instillation. The tumor take rate was 84.2%, formed initially on day 4 and remained NMIBC up to day 21. T1 photon densities were significantly higher than Ta (P < 0.01), and histological tumor volume was positively correlated with BLI photon density (r2 = 0.87, P < 0.01). The mTOR signaling pathway-related proteins were expressed in the bladder, and were correlated with the western blot results. Our results suggest successful establishment of an orthotopic mouse NMIBC model expressing the mTOR signaling pathway using KU-7-luc cells. This model is expected to be helpful to evaluate preclinical testing of intravesical therapy based on the mTOR signaling pathway against NMIBC.

Erratum: Correction of Acknowledgement. Establishment of an Orthotopic Mouse Non-Muscle Invasive Bladder Cancer Model Expressing the Mammalian Target of Rapamycin Signaling Pathway

We found an error in our published article.

An Epidemiologic Investigation of Shigella Sonnei Outbreak at a Primary School in Taegu city / 한국역학회지

PURPOSES: This study was conducted to determine the source of infection and mode of transmission of the shigellosis outbreak on March 27, 1998 at a primary school in Taegu city. METHODS: On-site interview using a standard questionnaire and rectal swab were conducted to 1,629 peoples who ate lunch on March 26 and 1,389 peoples who contacted with suspected cases. And bacteriological examination for 91 environmental materials and 25 food items were performed. RESULTS: Of the 1,629 persons who ate lunch on March 26, seventy three had culture-confirmed S. sonnei infection(first attack rate: 4.5%). And additional fifty four had shigellosis among those 1,389 persons who might be exposed to the suspected cases(second attack rate: 3.9%). A total of 730 persons who complained one of four typical symptoms or more were treated as suspected cases(first attack rate of suspected cases: 44.8%). S. sonnei was never isolated from water, foods, and other environmental materials. The median incubation period was estimated about two days. The common symptom reported were diarrhea(88.7%), fever(73.4%), abdominal pain(54.7%), and vomiting episode(38.4%) in order. The shorter duration of the outbreak and the large proportion of cases involving students who ate lunch on March 26 are consistent with fecal-oral transmission, although the limited epidemiologic data obtainable do not clearly define the route of transmission. CONCLUSIONS: Thus the outbreak reported here appear to be related to the unsanitary conditions of food facility in this school.

Death Orientation of the Korean Adult: Data was focused on residents who were living in urban area / 기본간호학회지

Death and dying of human being is a comprehensive system, and death orientation, the subjective meaning related to every component of the death system is developed throughout life. this study was designed and carried out to identify, describe and classify the orientations of Korean adult toward the death system. In an attempt to measure the subjective meaning of death and dying, unstructured Q-methodology was used. The 65 Q-statements developed by Kim(1994), used by Kim(1994) and Park(1996) were adopted as Q-population and 39 Q-statements were selected by the three researchers for Q-items for this study. Thirty-three P-samples were sampled from P-population of literature Korean men and women, 35 and 55 years of age, lived in urban Korea for the last 10 years. Sorting of the 39 Q-items according to the level of personal agreement, and a forced normal distribution into the 9 levels were carried out by the P-samples. the Z-scores of the Q-sort data were computed, and the principal components factor analysis by PC-QUANL Program were carried out. the demographic, socio-cultural and health-related attributes of the P-samples were descriptively analysed. Eight types of death orientation were identified : Type I ; "naturalist". Six P-samples. Death is a natural phenomena, to be accepted as it is and to follow its natural course. Prefer to be informed of all facts and possibilities concerning the course of dying and death to occur to self. Type II ; "life-after-life negator". Three P-samples. Time and process of death is the destiny of each person. Death means 'darkness' and 'end to every thing, the absolute end'. Yet, wish physical integrity at the dying and after death. Type III ; "life-after-life believer". Six P-samples. Men are travellers passing by this life bound to the life-after-life. Priority concerns are on the activities. to prepare self for the eternal life ahead. Disregard premature and sudden death. Type IV ; "here-now believer". Five P-samples. Positive regard to the cremation of the body and donation of the organs on death. Regard religious and customary post-mortem rituals meaningless. Negate life-after life. Type V ; "believer of rituals". Five P-samples. Death being accepted as a part of a natural end to, and destiny of human life. Concerned to ensure a dignified end to personal life and dignified post-mortem rituals. Type VI ; "Realist"(derived from Type I). Tow P-samples. Life and death as universal reality. The abrupt death at golden age at the peak of happiness is favored to avoid inevitable physical and mental distress of self and the family. Agreed to the cremation of the body. disregard rituals. Type VII ; "Fatalist"(derived from Type II). Five P-samples. Not favored, yet, all man are destined to death, the inevitable end of all living beings. to ensure dignified end by personal consummation, information. on one's dying and imminent death are to be shared. Type VIII ; "reality avoider"(derived from Type III. One P-sample. Negative to longevity, artificial prolongation of, meaningless and distressful life. Highly positive to post-mortem organ donation.

A Study of Factors Influencing Health Promoting Behavior and Quality of life in the Elderly / 간호학회지

The purpose of this study was to investigate the factors influencing health promoting behavior and quality of life in the elderly, to provide the basic data for health promoting intervention in order to improve quality of life. The subjects of this study were 51 elderly person over the age of 65, living in Seoul, Korea, during the period from November, 1997 to January, 1998. The instruments for this study were the health promoting behavior scale developed by Walker et (1987), the quality of life scale by RoyouJa(1988), the health concept scale by Laffrey(1986), the perceived health states scale by Lawston et al. (1992), the health value scale by Walston et al.(1978), the self esteem scale by Rogenberg(1965) and self efficacy scale by Sherer(1982). The instruments of this using descriptive statistics, t-test, Person correlation coefficients ANOVA and stepwise multiple regression. The results of this study are as follows; 1. The health promoting behavior showed significant positive correlation with health concept perception of health status, self esteem, internal health locus of control, self efficacy and quality of life in the elderly. 2. The quality of life showed significant positive correlation with health concept, perception of health status, self esteem, internal health locus of control, self efficacy in the elderly. 3. Stepwise multiple regression analysis revealed that the most powerful predictor of health promoting behavior was quality of life. A combination of quality of life, health concept, perceived health status, self esteem, internal health locus of control, and self esteem, internal health locus, and self efficacy accounted for 46% of the variance in health promoting behavior in the elderly. 4. Stepwise multiple regression analysis revealed that the most powerful predictor of quality of life in the elderly was self esteem. A combination of self esteem. health concept, perceived health status, health promoting behavior and self efficacy account for 56% of the variance in quality of life in the elderly. From the results of the study, the following recommendations are presented as follow : 1. Development of a health promoting program to improve quality of life in the elderly. 2. In developing the health promoting, the above major influencing factors be considered. 3. It is suggested that an education specialist in practice in the community be include in the program development.

A Classification of Death Orientation of Cancer Patient`s Family Members: A Q-Methodological Approach / 기본간호학회지

This study was designed to identify, describe and classify orientations of cancer patient's family members to death and to identify factors related to their attitudes on death. Death to the male is understood as a comprehensive system and believed to be highly subjective experience. Therefore attitude on death is affected by personalities. As an attempt to measure the subjective meaning toward death, the unstructured Q-methodology was used. Korean Death Orientation Questionnaire prepared by Kim was used. Item-reliability and Sorting reliability were tested. Forty five cancer patient's family members hospitalized in one university medical center in Seoul were sampled. Sorting the 65 Q-items according to the level of personal agreement; A forced normal distribution into the 11 levels, were carried out by the 45 P-samples. The demographic data and information related to death orientation of the P-sample was collected through face to face in depth interviews. Data was gathered from August 30 till September 22, 1995. The Z-scores of the Q-items were computed and principal component factor analysis was carried out by PC-QUANL Program. Three unique types of the death orientation were identified and labeled. Type I consists of twenty P-samples. Life and death was accepted as people's destiny. They firmly believed the existence of life after life. They kept aloof from death and their concern was facing the end of the life with dignity. They were in favor of organ donation. Type II consists of Nine P-samples. They considered that death was the end of everything and did not believed the life after life. They were very concerned about the present life. Type III consists of Sixteen P-samples. They regarded the death as a natural phenomena. And they considered that the man is just a traveller and is bound to head for the next life which is believed to be free of agony, pain or darkness. They neither feared death nor its process. Their concerns were on the activities to prepare themselves for the eternal-life after death. Thus, it was concluded that there were three distinctive type of attitudes on death among cancer patient family members, and their death attitudes were affected by demographic and socio-cultural factors such as sex, education, and religion.