The Relationship of Socioeconomic and Behavioral Risk Factors With Trends of Overweight in Korea / 예방의학회지

OBJECTIVES: Previous studies have shown that overweight (including obesity) has increased significantly in Korea in recent decades. However, it remains unclear whether this change has been uniform among all Koreans and to what extent socioeconomic and behavioral factors have contributed to this increase. METHODS: Changes in overweight were estimated using data from the 1998, 2001, 2005, 2007-2009, and 2010-2012 Korea National Health and Nutrition Examination Survey (n=55 761). RESULTS: Overweight increased significantly among men but not among women between 1998 and 2012. Changes in socioeconomic and behavioral factors over the time period were not associated with overall trends for both men and women. However, we found significant differences in the prevalence of overweight relative to key risk factors. For men, overweight increased at a significantly greater rate among the non-exercising (predicted probability [PP] from 0.23 to 0.32] and high-calorie (PP from 0.18 to 0.37) groups compared to their active and lower-calorie counterparts, respectively. For women, overweight increased only among the non-exercising (PP from 0.27 to 0.28) and low-income (PP from 0.31 to 0.36) groups during this period. CONCLUSIONS: These findings suggest that programs aimed at reducing overweight should target Korean men and women in specific socioeconomic and behavioral risk groups differentially.

In Vitro and In Vivo Radiosensitizing Effect of Valproic Acid on Fractionated Irradiation / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted in order to validate the radiosensitization effect of valproic acid, a biologically available histone deacetylase inhibitor, for fractionated radiation. MATERIALS AND METHODS: Radiosensitization effect of valproic acid was tested for the A549 cell line and U87MG cell line in vitro. Fractionated irradiation of 12 Gy in four fractions was administered on D2-5 with valproic acid, 150 mg/Kg, ip, bid for six consecutive days (D1-6) to A549 and U87MG tumors implanted in BALB/c-nude mice. A growth delay curve was formulated. RESULTS: Radiosensitization effect of valproic acid was found for both cell lines; A549 at 1.5 mM and 3.0 mM concentration and U87MG at 3.0 mM concentration. In growth delay analysis, a statistically significant radiosensitization effect was observed for both tumors (p < 0.001 for both tumors). Difference for change in slope for control and valproic acid versus radiotherapy and radiotherapy plus valproic acid showed borderline significance for the U87MG cell line (p=0.065), indicating beyond additive effect, whereas this difference was statistically insignificant for A549 tumor (p=0.951), indicating additive effect. CONCLUSION: Results of this study indicate that a radiosensitizing effect for fractionated radiotherapy of valproic acid for A549 and U87MG tumors in vivo is evident and that it may be more than additive for U87MG tumors. Further exploitation of histone deacetylase inhibitors in clinical trials is warranted.

Intravitreal Bevacizumab Injection in Diabetic Papillopathy

PURPOSE: To report a case where intravitreal bevacizumab injection was an effective treatment for diabetic papillopathy in a type 2 diabetic patient. CASE SUMMARY: A 47-year-old male with a 10-year history of diabetes mellitus type 2 presented to our clinic for evaluation of diabetic retinopathy. There were no subjective symptoms including blurred vision or visual defect, and best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/30 in the left eye. Fundus examination showed hyperemic optic disc swelling with telangiectatic new vessels, and fluorescein angiography leakage from the optic disc with neovascularization. The patient underwent fractionated panretinal photocoagulation. Ten days later, he complained of painless blurred vision with significant optic nerve head swelling and BCVA was 20/80 in the left eye. Intravitreal bevacizumab injection was administered, optic disc swelling was significantly decreased and BCVA improved to 20/30 after two months. CONCLUSIONS: Diabetic papillopathy with severe decreased visual acuity can be treated with intravitreal bevacizumab injection.

Comparative Analysis of the Humphrey Static Perimetry and the Goldmann Kinetic Perimetry: Application of the Humphrey Static Perimetry to Visual Disability Evaluation

PURPOSE: In the evaluation of visual field defect, Goldmann kinetic perimetry is the preferred method. However, in many cases, Humphrey static perimetry is performed for visual disability evaluation in Korea. In the present study we investigated the correlation between Goldmann kinetic perimetry and Humphrey static perimetry for disability evaluation using visual field score (VFS). METHODS: This study included 126 eyes, classified into the following groups: 60 eyes, normal group; 11 eyes, contraction of central visual field group; 42 eyes, irregular visual field group; 13 eyes, hemianopsia group. All subjects were examined with Goldmann kinetic perimetry and Humphrey static perimetry. We studied the correlation of the VFS between Goldmann kinetic perimetry and Humphrey static perimetry according to the Korean Academy of Medical Science Guides for Impairment Evaluation (KAMS Guides) and American Medical Association Guides for the Evaluation of Permanent Impairment (AMA Guides). RESULTS: Regarding contraction of central visual field group, Goldmann VFS, Humphrey VFS and extended Humphery VFS showed no statistical significance (AMA: p = 0.50, p = 0.30, KMAS: p = 0.36, p = 0.18. respectively). In the irregular visual field and hemianopsia groups, Goldmann VFS and Humphrey VFS showed statistical significance (AMA: p = 0.00, p = 0.00, KMAS: p = 0.00, p = 0.00. respectively). Goldmann VFS and extended Humphrey VFS showed no statistical significance (AMA: p = 0.13, p = 0.12, KMAS: p = 0.08, p = 0.99. respectively). CONCLUSIONS: The contraction of central visual field based on Humphrey static perimetry can be applied to visual disability evaluation. However, in the majority of cases, there is a difference between the two tests and Goldmann kinetic perimetry should be used first in the evaluation of visual field disability evaluation.

Sequence-Dependent Radiosensitization of Histone Deacetylase Inhibitors Trichostatin A and SK-7041 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This preclinical study is to determine whether the capacity of histone deacetylase (HDAC) inhibitors to enhance radiation response depends on temporal sequences of HDAC inhibition and irradiation. MATERIALS AND METHODS: The effects of HDAC inhibitors trichostatin A (TSA) and SK-7041 on radiosensitivity in human lung cancer cells were examined using a clonogenic assay, exposing cells to HDAC inhibitors in various sequences of HDAC inhibition and radiation. We performed Western blot of acetylated histone H3 and flow cytometry to analyze cell cycle phase distribution. RESULTS: TSA and SK-7041 augmented radiation cell lethality in an exposure time-dependent manner when delivered before irradiation. The impact of TSA and SK-7041 on radiosensitivity rapidly diminished when HDAC inhibition was delayed after irradiation. Radiation induced the acetylation of histone H3 in cells exposed to TSA, while irradiation alone had no effect on the expression of acetylated histone H3 in TSA-naive cells. Preirradiation exposure to TSA abrogated radiation-induced G2/M-phase arrest. When delivered after irradiation, TSA had no effect on the peak of radiation-induced G2/M-phase arrest. CONCLUSION: TSA and SK-7041 enhances radiosensitivity only when delivered before irradiation. Unless proven otherwise, it seems prudent to apply scheduling including preirradiation HDAC inhibition so that maximal radiosensitization is obtained.

Surgical Results of Modified Harada-Ito Operation for Excyclotorsion

PURPOSE: We evaluated the efficacy of the modified Harada-Ito operation for excyclotorsion in acquired superior oblique palsy patients after trauma. METHODS: This study represents a retrospective review of 10 eyes in 9 patients who were surgically treated for excyclotorsion. Cyclotorsion was measured with the double maddox-rod test and fundus photographies preoperatively and postoperatively. RESULTS: The median measured change in excyclotorsion before and after the surgery in the primary gaze was reduced from 15.67 +/- 6.00 to 4.78 +/- 3.42 according to fundus photographies and from 12.30 +/- 6.27 to 2.45 +/- 3.73 according to the double maddox-rod test. Subjective and objective changes in excyclotorsion werer not significantly different. CONCLUSIONS: The Modified Harada-Ito operation is an effective treatment for correcting excyclotorsion. Although not statistically significant, the amount of excyclotorsion on fundus photography is exaggerated. This point should be considered to achieve effective surgery.

A Case of Keratoconjunctival Chemical Injury from a Topical Anesthetic Ointment

PURPOSE: To report a case of keratoconjunctival chemical injury caused by exposure to EMLA(R) 5% cream. CASE SUMMARY: A 51-year-old woman presented with ocular pain and decreased visual acuity in her left eye after an autologous fat injection for forehead lifting. At her initial visit, her best corrected visual acuity was 20/40 in the left eye. Slit-lamp examination showed a diffuse corneal epithelial defect and conjunctival injection. Based on history of inadvertent seepage of EMLA(R) 5% cream into the left eye and clinical findings consistent with chemical injury, the patient was treated with antibiotics, steroids, and artificial tears. Two weeks after treatment, several corneal erosions remained, and best corrected visual acuity improved to 20/20. After two months, the corneal and conjunctival epithelia were healed. CONCLUSIONS: EMLA(R) 5% cream is commonly used as topical anesthetic ointment for dermatologic surgery, including laser procedures. The cream is highly alkaline and can cause chemical injury to the eye, thus extreme caution should be used when applying the cream to the eyelid or face.

Relationship between Metabolic Syndrome and Aging Male Symptoms in Middle-Aged Males in Korea / 가정의학회지

BACKGROUND: Metabolic syndrome is regarded as a risk factor of cardiovascular disease. We observed and compared aging males symptoms (AMS) between healthy and metabolic syndrome patients in middle-aged Korean men to evaluate clinical significance of AMS. METHODS: From May 2009 to July 2009, 171 middle-aged men (over 40 years-old) who visited a health promotion center of a university hospital in Gyeonggi Province were enrolled in study. The subjects were divided into two groups; metabolic syndrome (N = 87) vs. control (N = 84) and measured the aging male symptoms (AMS) scale. AMS were also grouped according to its severity. RESULTS: There were no significant differences except, weight, body mass index between two groups. In AMS severity, 'severe' group show higher prevalence of metabolic syndrome. And the group of metabolic syndrome gets higher AMS score than control. Among the five constitutive factors of metabolic syndrome, the prevalence of fasting blood sugar (> or = 100 mg/dL) and triglyceride (> or = 150 mg/dL) level is higher 'moderates' and 'severe' groups in AMS severity. In the subscale analysis of AMS, there are significant differences between two groups in sexual and somato-vegitative axis, but are not in psychological axis. With age-adjusted analysis, the results still show same trend. CONCLUSION: It might be necessary to approach aging males symptoms comprehensively during the management of metabolic syndrome in middle-aged men. And it could be helpful in treatment to recognize and control metabolic syndrome factors for the patients with severe aging males symptoms.

Reliability and Validity of the Korean Version of the Penn State Worry Questionnaire in Primary School Children

Worry is a generalized psychological phenomenon seen among most people. When worry is excessive and nearly uncontrollable, people usually suffer psychological pain. The Penn State Worry Questionnaire for Children (PSWQ-C) was developed to measure worry objectively. It comprises 14 items for measuring excessive, generalized, and uncontrollable worry in children. This study, conducted with a large group of elementary children (3rd through 6th graders, ages 8-12 yr; N=973), investigated the reliability and validity of the Korean version of the Penn State Worry Questionnaire for Children (PSWQ-CK). The PSWQ-CK showed high reliability by test-retest and also excellent internal consistency results. To examine the validity of the PSWQ-CK, we calculated its correlation with the Revised Children's Manifest Anxiety Scale (RCMAS). The PSWQ-CK had a higher correlation with the worry/oversensitivity factor than with other subscales of the RCMAS, and it showed no correlation with the lie factor. When 3 reversed PSWQ-CK items were eliminated, the instrument showed higher internal consistency. However, this did not improve its correlation with other anxiety-measuring tools. In conclusion, the PSWQ-CK's reliability and validity were satisfactory, and it is a useful tool for objectively measuring the worry of Korean children of this age group.

In vivo Radiosensitization Effect of HDAC Inhibitor, SK-7041 on RIF-1 Cell Line / 대한방사선종양학회지

PURPOSE: To test the radiosensitizing effect of the newly synthesized novel histone deacetylase inhibitor, SK-7041 in vivo. MATERIALS AND METHODS: The RIF-1 cell line was implanted into the back of a 6-week-old female C3H mouse, intradermally. The mice were grouped into control, drug, radiation (RT), and RT+drug group. SK-7041, 4 mg/kg was administered intraperitoneally for six cycles every 12 hours for mice in the drug and RT+drug group. An identical volume of phosphate buffered saline (PBS) was administered at the same frequency to mice in the control and RT groups. A single 5 Gy fraction was delivered to mice in RT and RT+drug group 6 hours after the fourth delivery. The volume of the implanted tumor was measured every 2~3 days to formulate the growth delay curve. RESULTS: For the control, drug, RT, and RT+drug groups, the average duration for implanted tumor to reach a volume of 1,500 mm3 was 10 days, 10 days, 9 days, and 12 days, respectively. Moreover, the tumor volume on D14 was 276.7 mm3, 279.9 mm3, 292.5 mm3, and 185.5 mm3, respectively (p=0.0004). The difference for the change in slope for the control and drug versus the RT and RT+drug groups were borderline significant (p=0.0650). CONCLUSION: The results of this study indicate that SK-7041 has a radiosensitizing effect for the RIF-I cell line in vivo at a low concentration and this effect may be synergistic. Implementing this result to clinical trial is warranted.

Relationship between Sleep Quality and Metabolic Syndrome and Infl ammatory Markers in Middle-aged Men in Korea / 가정의학회지

BACKGROUND: As many studies revealed that sleep restriction is associated with obesity and insulin resistance and blood pressure elevation, the relationship between sleep and metabolic syndrome has been concerned. But little information exists on correlation between sleep quality and metabolic syndrome. In this study, we investigated the relationship between sleep quality measured by Pittsburgh Sleep Quality Index (PSQI) and metabolic syndrome. METHODS: A total of 100 middle-aged male adults were included in this study from March to May 2008 at a health promotion center. The subjects were divided into two groups of poor sleeper group (N = 47) vs. good sleeper group (N=53) by PSQI global score. The components of metabolic syndrome and inflammatory markers were measured. The metabolic syndrome criterion of the AHA/NHLBI 2005 was adopted. RESULTS: There was no significant differences in baseline characteristics between the two groups. HDL-cholesterol was significantly lower in the poor sleeper group compared to the good sleeper group (P < 0.05). The negative correlation was noted between subjective sleep quality score with HDL-cholesterol (P < 0.05). There was a positive correlation between sleep latency and triglyceride and a negative correlation with HDL-cholesterol (P < 0.05). The longer sleep latency, the higher level of white blood cell count was observed (P = 0.001). CONCLUSION: The above data suggest that a possible causal interaction between poor sleep quality and lower HDL-cholesterol of metabolic syndrome components and higher level of white blood cell counts. Further prospective studies regarding the change in the components of metabolic syndrome and the risk factors of cardiovascular diseases after relieving sleep disturbance seem to be warranted.

Effect of Cerebral Motor Cortex Stimulation in Amyotrophic Lateral Sclerosis Model: A Preliminary Controlled Study

OBJECTIVE: To observe the effect of the depolarizing stimulation in amyotrophic lateral sclerosis (ALS) mouse model on the survival and behavioral performance. METHOD: Transgenic male mouse model of ALS at the age of 9~11 weeks were divided into sham control group (n=10) and stimulation group (n=9). Electrode was implanted in the motor cortex in left hemisphere. Movement thresholds (MT) were regularly checked. Half threshold of MT, unipolar, and continuous electrical stimulation (frequency, 50 Hz; pulse duration, 220micron s) was delivered through implanted electrode. Behavioral tests including Rota-rod and Paw-grip endurance were checked every day. RESULTS: Induction of symptom was delayed in 8 days in stimulation than sham control group. However, there was no significant difference in survival in both groups. Behavioral tests showed that stimulation group is significantly better than sham group in Rota-rod (11~15 weeks) and in grip endurance (11~14, 16 weeks). MT was always between 1.0 volt and 3.2 volt in sham group, however, MT was between 0.8 volt and 2.8 volt in stimulation group. MT was jumped up around the time of death in both groups. CONCLUSION: Electrical stimulation is considered to be one of possible trial methods in ALS model. However, parameters of the stimulation in the experiment should be modified for better results.

Relations between Worry, Attachment Styles and Perceived Parental Rearing in Primary School Children

BACKGROUND: Worry, a core feature of anxiety disorder, is shown in not only children with anxiety disorder but also normal children. This study was conducted to determine the relationship between worry and family environment factors, especially, perceived parental rearing and attachment styles among children. METHODS: Five hundred and nine children participated in this study among 549 children in third, fourth, fifth and sixth grades in two primary schools located in Seoul and Seongnam from October 2007 to December 2007. Forty children did not agree with participation (rejection rate: 7.3%). Their degrees of worry, attachment styles and perceived parental rearing were investigated with questionnaires. RESULTS: The reliability of a questionnaire asking children's worry, PSWQ-C and a questionnaire asking perceived parental rearing, modified EMBU-C was appropriate with internal consistency (Cronbach's alpha of PSWQ-C: 0.92, Cronbach's alpha of modified EMBU-C: 0.68~0.89). Around 22.4% of children had insecure attachment (avoidant or ambivalent attachment) and scores of worry were high in both girls and boys. When children perceived their parental rearing behavior as anxious rearing, they were classified to have ambivalent attachment in many cases by themselves. And when they perceived the rearing as rejection many of them were classified to have avoidant or ambivalent attachment by themselves. Worry showed a significantly negative correlation in the cases where children answered their perceived parental rearing as emotional warmth and showed a significantly positive correlation with rejective and anxious rearing. CONCLUSION: This study found that children's worry was closely related with their perceived parental rearing and attachment styles. If the children's attachment, which has been developed while they have grown up, was insecure and they did not perceive parental rearing as emotional warmth, the intensity of worry, a core symptom of anxiety disorder, increased.

Relationship between Mammographic Dense Breast and Other Risk Factors of Breast Cancer in Korean Women

BACKGROUND: Several studies have demonstrated that mammographic dense breast is related to the risk of breast cancer and is associated with decreased mammographic sensitivity and specificity. In contrast, studies concerning women with dense breast are virtually non-existent. This study was conducted to evaluate the relationship between mammographic dense breast and other risk factors of breast cancer, and to make a plan for individualized strategies in high risk populations. METHODS: The study subjects were 565 women, aged 20~70 years, who had a screening mammogram from April 2005 to August 2005 at a health promotion center. Data of demographic factors, breast caner risk factors and menstrual status were collected by the self-administered questionnaire. Mammographic breast density was classified according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) fours categories, as measured by the proportion of glandular tissues within the total breast tissue. RESULTS: By BI-RADS categories, 'entirely fat' were 46, 'scattered fibroglandular' were 96, 'heterogenous dense' were 332 and 'extremely dense' were 91 (16.1%). Univariate analysis showed that age, occupation, education level, body mass index, age at menarche, parity, breast feeding, menopausal status and triglyceride had significantly related to dense breast (P<0.05). In the multivariate logistic analysis, only low body mass index (P<0.001), low parity (P=0.009, 0.038) and premenopausal status (P=0.001) were significantly associated with dense breast. CONCLUSION: In Korean women, dense breast was significantly associated with low body mass index, low parity and premenopausal status. Therefore, if women with dense breast have these risk factors, they need to be managed more intensively with regular screening, breast sonogram, and lifestyle modification.

Change of CAVI in Maintenance Hemodialysis Patients / 대한신장학회잡지

BACKGROUND:CAVI, Cardio Ankle Vascular Index, has been proposed as an independent marker of arterial stiffness regardless of the blood pressure. We measured the CAVI of hemodynamically unstable patients on maintenance hemodialysis and at the same time measured other pulse pressure-related parameters in order to study their correlations with each other. METHODS:We studied 85 patients undergoing maintenance hemodialysis over 3 months. We categorized patients into 4 subgroups: Diabetes+Hypotension (N= 12), Diabetes+Normal blood pressure (N=16), Non- diabetes+Hypotension (N=15), and Non-diabetes+Normal blood pressure (N=42). Using automatic waveform analyzer, we measured CAVI and pulse pressure- related markers twice, before and after the hemodialysis session, and observed the change. RESULTS:After the dialysis, CAVI did not change despite the decreased mean blood pressure. Yet both brachial and ankle pulse pressure dropped significantly (4.34+/-15.22 mmHg, 11.50+/-20.65 mmHg, p<0.01). PEP (Pre-Ejection Period) on the other hand, remarkably increased (12. 13+/-22.18 msec) while ET (Ejection Time) showed considerable decrease (35.86+/-45.68 msec), and PEP/ ET ratio increased as well. Predialysis CAVI was significantly higher in Diabetes group than in Non-diabetes (11.02+/-2.33 vs. 8.20+/-1.87, p<0.001). However, no significant difference of CAVI was observed between Hypotension and Normal blood pressure groups. Diabetes+Hypotension Group displayed reduction in CAVI after dialysis with marginal significance (0.68+/-1.07, p=0.05) whilst PEP, ET and PEP/ET ratio showed no significant change compared to other groups. CONCLUSION:CAVI, a newly developed marker of arterial stiffness, is expected to be useful in prediction of the cardio-vascular risk and prognosis of patients undergoing hemodialysis.

The Clinical Significance of Aortic Pulse Wave Velocity in Korean Adults

BACKGROUND: As recent studies show that pulse pressure (PP) is the most potent predictor of cardiovascular diseases, many studies focus on the non-invasive methods to evaluate arterial stiffness influencing on pulse pressure. This study attempted to show the relationship between cardiovascular risk factors and aortic pulse wave velocity (PWV) as a classical factor of arterial stiffness in Korean adults. METHODS: The subjects were 305 adults who had visited a health care center of a university medical center in Suwon from December, 2003 to April, 2004. We had measured the aortic pulse wave velocity through auto PWV analyzer (PP-1000, Hanbyul Meditech, Korea) and had compared the relationships with smoking, total cholesterol, high density lipoprotein, low density lipoprotein, body mass index, sex, age, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and fasting glucose. RESULTS: There were positive correlation between aortic pulse wave velocity and age (P=0.001), fasting blood sugar (P=0.013), systolic blood pressure (P=0.007), diastolic blood pressure (P=0.038), mean blood pressure (P=0.012), pulse pressure (P=0.035), total cholesterol (P=0.009), low density lipoprotein (P=0.023). There were significant differences of the groups by sex (P=0.029). CONCLUSION: The estimation of the aortic pulse wave velocity (PWV) using the auto PWV analyzer (PP-1000, Hanbyul Meditech, Korea) seems to be a useful diagnostic method of early detection of atherosclerosis for management and prevention of cardiovascular diseases. In future more data about correlations between cardiovascular risk factors and pulse wave velocity and methods managing these factors, and more studies for determining the meaningful values of pulse wave velocity, in larger cases are needed.

Relationship between Fatigue Severity and Heart Rate Variability in Middle-Aged Male Workers / 대한산업의학회지

OBJECTIVES: This study investigated the relationship between the severity of fatigue and the cardiac autonomic function by analyzing the heart rate variability on middle-aged male workers. METHODS: The severity of fatigue and heart rate variability were assessed with the control measures of age, body mass index, blood pressure, alcohol consumption, smoking history, regular exercise on 82 healthy middle-aged male workers in an annual health checkup. The severity of fatigue was evaluated by the Fatigue Severity Scale (FSS), which was developed by Krupp. The 5-minute electrocardiographic recordings were analyzed as a function of the time and the frequency domain methods of the heart rate variability (HRV). Standard Deviation of the NN intervals (SDNN), Root-Mean-Square of Successive Differences (rMSSD), Total Power (TP), Low Frequency (LF: 0.04~0.15 Hz) power, High Frequency (HF: 0.15-0.4 Hz) power, LF/HF ratio were used as the indices of the HRV. For a comparison of autonomic nervous functions and other variables, the subjects were divided into three fatigue groups based on the FSS score as follows: low (N=31), moderate (N=33), high (N=18) fatigue groups. RESULTS: There were no significant differences in age, blood pressure, heart rate, body mass index, alcohol consumption, or regular exercise except for the smoking history among the groups. In addition, there were no significant differences in the time domain analysis (SDNN, rMSSD) of HRV among the groups. Spectral analysis of the HRV showed that the mean amplitudes of the HF and LF component were lower in the high fatigue group, whereas there was no significant difference in the LF/HF ratio among the fatigue groups. There were no significant differences in the HRV indices between the smoking and non-smoking groups. No significant interacting effects between the severity of fatigue and smoking on the HRV were observed. CONCLUSIONS: The association between severe fatigue and the reduced high and low frequency components of the HRV in middle-aged male workers reflects a dysregulation of the cardiac autonomous control. Although the pathophysiological mechanism of this association remains unclear, these results might explain their increased risk for cardiovascular disease. However, these effects need to be confirmed through a well-designed prospective study.

Enhancement of Radiation Effects by Flavopiridol in Uterine Cervix Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line. MATERIALS AND METHODS: Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone. RESULTS: The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation. CONCLUSION: Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.

Leptomycin B Increases Radiosensitization by Trichostain A in HeLa Cells / 대한방사선종양학회지

PURPOSE: Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components of anticancer therapy and their radiosensitizing effects have become evident. Specific HDIs are now available that preferentially inhibit specific HDAC classes; TSA inhibits Class I and II HDACs, and SK7041 inhibits Class I HDACs. MATERIALS AND METHODS: We tested the differential radiosensitization induced by two different classes of HDIs in HeLa cells. We next tested the hypothesis that p53 expression in cancer cells may influence the susceptibility to HDIs by using pharmacologic modification of the p53 status under an isogenic background. RESULTS: It is interesting that p53 expression in the HeLa cells clearly increased the degree of radiosensitization by TSA compared to that of the class I specific inhibitor SK7041. This suggests that p53 may, in part, be responsible for the mechanistic role for the greater radiosensitization induced by Class I & II inhibitors compared to that of the class I specific inhibitors. Thus, these studies are useful in distinguishing between events mediated solely by the Class I HDACs versus those events involving the other classes of HDACs as well. CONCLUSION: The anticancer efficacy of targeting Class I and II HDACs, in conjunction with radiation therapy, may be further enhanced by the restoration of p53 expression.

A Histone Deacetylase Inhibitor, Trichostatin A, Enhances Radiosensitivity by Abrogating G2/M Arrest in Human Carcinoma Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction. MATERIALS AND METHODS: A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed. RESULTS: TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner. CONCLUSION: The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiationinduced G2/M arrest.