The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.
Caenorhabditis elegans* ; Drug Discovery* ; Drug Evaluation, Preclinical ; Germ Cells ; Humans ; Infertility ; Mass Screening ; Molecular Biology ; Neoplastic Stem Cells ; Phenotype ; Social Control, Formal ; Stem Cell Niche ; Stem Cells ; Vertebrates

We retrospectively analyzed the prognostic factors on overall survival (OS) in patients with brain metastasis (BM) and evaluated the role of combined primary tumor and extracranial metastasis (ECM) status as a constituent factor for prognostic index. This study involved 897 patients with BMs who underwent radiotherapy between April 2003 and December 2009. Among the clinical parameters, multivariate analysis showed that age, Karnofsky performance status (KPS), combined primary tumor and ECM status, number of BMs, and treatment group were significant prognostic factors for OS (P < 0.05). To compare the discriminatory ability of 5 prognostic indices, i.e., recursive partitioning analysis (RPA), basic score for BMs (BSBM), score index for radiosurgery (SIR), graded prognostic assessment (GPA), and modified GPA including the combined primary tumor and ECM status (mGPA), the Akaike information criteria (AIC) were calculated. The mGPA showed the lowest AIC value, followed by RPA, GPA, SIR, and BSBM, in that order. It is implicated that modified score of pre-existing factors (i.e., age and KPS) and addition of the combined primary tumor and ECM status to the prognostic index can improve its discriminatory ability and the combined primary tumor and ECM status may be useful as one of constituent factors for prognostic index.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Brain Neoplasms/*mortality/radiotherapy/secondary ; Breast Neoplasms/pathology ; Female ; Follow-Up Studies ; Humans ; Karnofsky Performance Status ; Lung Neoplasms/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Tomography, X-Ray Computed

OBJECTIVES: This study estimated the association of cardiovascular health behaviors with the risk of all-cause and cardiovascular disease (CVD) mortality in middle-aged men in Korea. METHODS: In total, 12 538 men aged 40 to 59 years were enrolled in 1993 and followed up through 2011. Cardiovascular health metrics defined the following lifestyle behaviors proposed by the American Heart Association: smoking, physical activity, body mass index, diet habit score, total cholesterol, blood pressure, and fasting blood glucose. The cardiovascular health metrics score was calculated as a single categorical variable, by assigning 1 point to each ideal healthy behavior. A Cox proportional hazards regression model was used to estimate the hazard ratio of cardiovascular health behavior. Population attributable risks (PARs) were calculated from the significant cardiovascular health metrics. RESULTS: There were 1054 total and 171 CVD deaths over 230 690 person-years of follow-up. The prevalence of meeting all 7 cardiovascular health metrics was 0.67%. Current smoking, elevated blood pressure, and high fasting blood glucose were significantly associated with all-cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined were 35.2% (95% confidence interval [CI], 21.7 to 47.4) and 52.8% (95% CI, 22.0 to 74.0) for all-cause and CVD mortality, respectively. The adjusted hazard ratios of the groups with a 6-7 vs. 0-2 cardiovascular health metrics score were 0.42 (95% CI, 0.31 to 0.59) for all-cause mortality and 0.10 (95% CI, 0.03 to 0.29) for CVD mortality. CONCLUSIONS: Among cardiovascular health behaviors, not smoking, normal blood pressure, and recommended fasting blood glucose levels were associated with reduced risks of all-cause and CVD mortality. Meeting a greater number of cardiovascular health metrics was associated with a lower risk of all-cause and CVD mortality.
Adult ; Blood Glucose/analysis ; Blood Pressure ; Body Mass Index ; Cardiovascular Diseases/epidemiology/*mortality ; Cohort Studies ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Life Style ; Male ; Middle Aged ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Smoking

Authors evaluated pulmonary tuberculosis (PTB) history as a risk factor for lung cancer in current male smokers in a prospective, population-based cohort study. The subjects were the 7,009 males among the participants in the Seoul Male Cancer Cohort Study for whom there was full information on PTB history and smoking habits. With a 16-yr follow-up, 93 cases of lung cancer occurred over the 99,965 person-years of the study. The estimated relative risk (RR) of PTB history of current smokers in lung cancer after adjusting for three confounders - intake of coffee and tomatoes, and age at entry - was 1.85 (95% CI: 1.08-3.19). The observed joint RRs and attributable risks (ARs) across strata of three confounders were greater than the expected, indicating a positive interaction. Thus a history of PTB in current smokers may be another risk factor for lung cancer. Based on a synergic interaction, a heavy male smoker with a PTB history would be expected to belong to the group at high risk of lung cancer.
Adult ; Cohort Studies ; Follow-Up Studies ; Humans ; Lung Neoplasms/*diagnosis/etiology ; Male ; Middle Aged ; Prospective Studies ; Republic of Korea ; Risk Factors ; *Smoking ; Time Factors ; Tuberculosis, Pulmonary/complications/*diagnosis

The relative risk (RR) of smoking and mortality of lung cancer in British doctors was previously reported to have increased throughout a 40-yr period. Here, we evaluated this RR based on the incidence of lung cancer in Korean men using a longer follow-up period. We compared our data to the RR reported in a study using a 10-yr follow-up period; the subjects and methods were identical to those of the previous paper with the exception of the follow-up period, which ended on December 31, 2008. We found that the RR of smoking habits in patients with lung cancer did not increase, and that the data showed narrowing 95% confidence intervals over a longer observation in Korean men. Estimated lung cancers attributable to smoking were 55.6%. These results highlight the need for an intervention program to help patients quit smoking in Korea.
Asian Continental Ancestry Group ; Cohort Studies ; Follow-Up Studies ; Humans ; Incidence ; Lung Neoplasms/*epidemiology ; Male ; Republic of Korea/epidemiology ; Risk ; *Smoking

PURPOSE: To estimate the current cancer burden in Korea, newly diagnosed cancer cases and cancer incidence rates were calculated for the years 2003~2005. MATERIALS AND METHODS: The cancer incidence cases and rates were calculated from the Korea National Cancer Incidence Database. Crude and age-standardized incidence rates were calculated by gender for specified cancer sites in 5-year age groups. RESULTS: From 2003 to 2005, 398,824 cases of cancer were newly diagnosed in Korea (218,856 in men and 179,968 in women). For all sites combined, the crude incidence rate (CR) was 300.0 and 248.2 for men and women and the age-standardized incidence rate (ASR) was 297.0 and 191.2 per 100,000, respectively. Among men, five leading cancers were stomach (CR 66.0, ASR 64.2), lung (CR 48.5, ASR 50.3), liver (CR 44.9, ASR 42.1), colon and rectum (CR 37.9, ASR 37.2), and prostate cancer (CR 12.7, ASR 13.8). Among women, five leading cancers were breast (CR 37.3, ASR 29.0), thyroid (CR 36.2, ASR 28.8), stomach (CR 34.1, ASR 25.4), colon and rectum (CR 28.0, ASR 21.1), and lung cancer (CR 17.9, ASR 12.8). In the 0~14-year-old group, leukemia was the most common in both sexes; in the 15~34 group, the most common cancer was stomach cancer for men and thyroid cancer for women; in the 35~64 group, stomach cancer for men and breast cancer for women; among those 65 and over, lung cancer for men and stomach cancer, for women, respectively. CONCLUSION: The cancer incidence rates have increased in recent years, and more cancers are expected to develop as Korea is quickly becoming an aged society. The cancer incidence statistics in this report can be used as an important source to effectively plan and evaluate the cancer control program in Korea.
Aged ; Breast ; Breast Neoplasms ; Colon ; Female ; Humans ; Incidence ; Korea ; Leukemia ; Liver ; Lung ; Lung Neoplasms ; Male ; Prostatic Neoplasms ; Rectum ; Stomach ; Stomach Neoplasms ; Thyroid Gland ; Thyroid Neoplasms

PURPOSE: Since the revised Cancer Act of October 2006, cancer registration was reactivated, based on the Statistics Law. MATERIALS AND METHODS: The incidence of cancer during 2002 was calculated on the basis of the information available from the National Cancer Incidence Database. Crude and age-standardized rates were calculated by gender for 18 age groups (0~4, 5~9, 10~14, every five years, 85 years and over). RESULTS: The overall crude incidence rates (CRs) were 269.2 and 212.8 per 100,000 for males and females, and the overall age-standardized incidence rates (ASRs) were 287.8 and 172.9 per 100,000, respectively. Among males, the five leading primary cancer sites were stomach (CR 62.4, ASR 65.7), lung (CR 45.4, ASR 51.0), liver (CR 43.2, ASR 43.7), colon and rectum (CR 30.7, ASR 32.7), and prostate (CR 8.0, ASR 9.6). Among females, the most common cancer sites were breast (CR 33.1, ASR 26.9), followed by stomach (CR 32.8, ASR 26.0), colon and rectum (CR 23.1, ASR 18.5), thyroid (CR 19.1, ASR 15.7), and uterine cervix (CR 18.2, ASR 14.7). In the 0~14 age group, leukemia was the most common cancer for both genders. For males, stomach cancer was the most common cancer in the 15~64 age-group, but lung cancer was more frequent in men 65 or older. For females, thyroid cancer among the 15~34 age-group, breast cancer among 35~64 age-group and stomach cancer in women 65 years or older were the most common forms of cancer for each age group. The quality indices for the percentage of deaths, by death certificate only, were 4.7% for males and 4.5% for females. CONCLUSIONS: Since the National Cancer Incidence Database was started, the annual percent change of cancer cases increased by 4.8% (4.1% for males, 5.7% for females) during 1999~2002. This value reflects the increase in prostate cancer for males and breast and thyroid cancer in females during 2002. The timely reporting of improved quality of cancer registration is needed for evidence-based decisions regarding cancer control in Korea.
Breast ; Breast Neoplasms ; Cervix Uteri ; Colon ; Death Certificates ; Female ; Humans ; Incidence* ; Jurisprudence ; Korea* ; Leukemia ; Liver ; Lung ; Lung Neoplasms ; Male ; Prostate ; Prostatic Neoplasms ; Rectum ; Stomach ; Stomach Neoplasms ; Thyroid Gland ; Thyroid Neoplasms

Lung cancer is the leading cause of cancer deaths in Korea. The aim of this study was to estimate lung cancer risk of cigarette smoking in Korean men by a 10-yr follow-up prospective cohort study using the primary databases. The number of subjects was 14,272 men, who had full information of smoking habits among participants in the Seoul Male Cancer Cohort Study (SMCC). Total 125,053 personyears were calculated by determining the number of days from the start of followup, January 1, 1993, until the date of lung cancer diagnosis, death from another cause, or the end of follow-up, December 31, 2002, followed by converting the number of days to years. The information of outcome was obtained by the database of Korea Central Cancer Registry, Seoul Regional Cancer Registry, and Korea Statistical Office. The relative risk (RR) and its 95% confidence interval (CI) values of smoking were calculated using Cox proportional hazards regression stratified on potential confounders. During the follow-up periods, 78 cases of lung cancer occurred. The cigarette smoking is the major risk factor and increases the 4.18-fold risk of lung cancer in Korean men. In order to control lung cancer, intervention of quitting smoking is needed.
Adult ; Cohort Studies ; Follow-Up Studies ; Humans ; Korea ; Lung Neoplasms/*diagnosis/*etiology ; Male ; Middle Aged ; Proportional Hazards Models ; Risk ; Risk Factors ; *Smoking ; Treatment Outcome

PURPOSE: The first Korean national population- based cancer registry using nationwide hospital-based recording system and the regional cancer registries provided the source to obtain national cancer incidences for the period 1999~2001. MATERIALS AND METHODS: The incidence of cancer in Korea was calculated based on the Korea Central Cancer Registry database, data from additional medical record review survey, the Regional Cancer Registry databases, site-specific cancer registry databases, and cancer mortality data from the Korea National Statistical Office. Crude and age-standardized rates were calculated by sex for 18 age groups. RESULTS: The overall crude incidence rates (CR) were 247.3 and 188.3 per 100, 000 for men and women and the overall age-standardized incidence rates (ASR) were 281.2 and 160.3 per 100, 000, respectively. Among men, five leading primary cancer sites were stomach (CR 58.6, ASR 65.6), lung (CR 42.1, ASR 50.9), liver (CR 41.9, ASR 44.9), colon and rectum (CR 24.2, ASR 27.3) and bladder (CR 7.7, ASR 9.2). Among women, the most common cancers were stomach (CR 30.8, ASR 25.8), breast (CR 25.7, ASR 21.7), colon and rectum (CR 19.6, ASR 16.7), uterine cervix (CR 18.4, ASR 15.5), and lung cancer (CR 15.1, ASR 12.4). In 0~14 age group, leukemia was most common for both sexes. For men, stomach cancer was most common in 15~64 age group, but lung cancer was more frequent for over 65 age group. For women, thyroid cancer in 15~34 age group, breast cancer in 35~64 age group, and stomach cancer in over 65 age group were most common for each age group. The proportions of death certificate only were 7.5% for men and 7.4% for women. CONCLUSION: This is the first attempt to determine the national cancer incidence and this data will be useful to plan for research and national cancer control in Korea.
Breast ; Breast Neoplasms ; Cervix Uteri ; Colon ; Death Certificates ; Female ; Humans ; Incidence* ; Korea* ; Leukemia ; Liver ; Lung ; Lung Neoplasms ; Male ; Medical Records ; Mortality ; Rectum ; Registries ; Stomach ; Stomach Neoplasms ; Thyroid Neoplasms ; Urinary Bladder

OBJECTIVE: To evaluate the learning achievement and satisfaction levels for the Field Epidemiology Specialist Training Program (FESTP), on infectious disease control between March 19 and October 31, 2002. METHODS: The FESTP was designed as a set of 84 hours curricula including lectures, discussions, self-studies, and field practicals, and organized both centrally and locally by the Division of Communicable Disease Control of the National Institute of Health and 11 universities. Before and after the program, a questionnaire survey on the educational need (49 items) and satisfaction (15 items) was conducted on 484 trainees, who were responsible for communicable disease control and immunization at 242 regional health centers. The data were analyzed with paired t-tests for comparison of the educational needs between the pre and post scores. RESULTS: The average score for satisfaction was 3.06 out of 5.0; with relatively higher scores for sincerity (4.10) and professionalism (4.01) of the tutors, adequacy (3.54) and clearness (3.51) of the evaluation criteria, usefulness (3.54) and fitness (3.52) of the contents, but with relatively lower satisfaction for schedule (2.96) and self-studies (2.91). The average for requirement for education improved, as shown by the decrease from 2.72 to 2.22 (p< .0001) with the biggest decrease in the outbreak investigation from 2.60 to 2.08. CONCLUSION: The FESTP was evaluated as being effective, the trainees showed moderate satisfaction and decrease educational needs. However, the actual schedules and self-studies should be rearranged to improve the satisfaction level.
Appointments and Schedules ; Communicable Disease Control ; Communicable Diseases ; Curriculum ; Education* ; Epidemiology* ; Immunization ; Learning ; Lectures ; Professionalism ; Specialization*