Gelatinase A is a member of the matrix metalloproteinases that play an important role in cancer invasion and metastasis. In the course of screening gelatinase A inhibitors from microbial sources, a fungal strain PT-262 showed a strong inhibitory activity. The strain was identified as Chaunopycnis alba on the basis of its morphological characteristics. The inhibitor was isolated from acetone extract of mycelial cake by sequential chromatographies on MCI-gel, Sephadex LH-20, and a reverse-phase HPLC column. The purified inhibitor was identified as pyridoxatin by its physico-chemical properties and spectroscopic analysis. Pyridoxatin is not a peptide analog and has cyclic hydroxamic acid moiety. It inhibited activated gelatinase A with an $IC_{50}$ value of 15.2 ${\mu}M$ using fluorescent synthetic peptide. It also had a strong cytotoxicity against human cancer cell lines in vitro. Furthermore, this compound inhibited DNA synthesis with an $IC_{50}$ value of 2.92 ${\mu}M$ in PC-3 prostate cancer cells by [$^3H$]thymidine incorporation assay.
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.
Yie, Ga-Eun;Kim, An Na;Cho, Hyun Jeong;Kang, Minji;Moon, Sungji;Kim, Inah;Ko, Kwang-Pil;Lee, Jung Eun;Park, Sue K.
Korean Journal of Community Nutrition
/
v.26
no.3
/
pp.211-227
/
2021
Objectives: We aimed to examine the association between the relative preference for vegetables and meat and cancer incidence, in a population-based retrospective cohort in Korea. Methods: We included 10,148,131 participants (5,794,124 men; 4,354,007 women) who underwent national health screening between 2004 and 2005 from the National Health Information Database of the National Health Insurance Service (NHIS-NHID). Participants were asked whether they preferred consuming 1) vegetables more often, 2) both vegetables and meat or 3) meat more often. Participants were followed up to Dec. 31, 2017. All cancer and eighteen common cancer cases were identified through the code from the International Classification of Diseases, 10th revision. We estimated sex-specific relative risks and 95% confidence intervals, adjusting for age, body mass index, alcohol consumption, smoking, physical activity, and income level. Results: During an average follow-up of 12.4 years, 714,170 cancer cases were documented. In men, consuming meat more often was associated with lower risk of esophageal, liver, and stomach cancers, but higher risk of lung and kidney cancers. Consuming both vegetables and meat was associated with higher risk of prostate cancer, but with lower risk of esophageal, liver, and stomach cancers in men. In women, consuming meat more often was associated with a higher risk of colorectal cancer and breast, endometrial, and cervical cancers diagnosed before the age of 50. Consuming both vegetables and meat was associated with lower risk of liver cancer in women. Conclusions: Our study suggests a potential link between vegetable and meat intake and cancer incidence in the Korean population. Further investigation on the association between the intake of specific types of vegetables and meat and cancer risk in Korean prospective cohort studies is needed.
In the course of screening program for VHR DS-PTPase (dual-specificity protein tyrosine phosphatase) from natural sources, Gastrodia elata was selected. One compound showing potent inhibitory activity was isolated by the solvent extraction and column chromatography including silica gel, ODS RP-18, Sephades LH-20, and HPLC. This compound was identified as baicalein by several NMR techniques such as $^1H-NMR$, $^{13}C-NMR$, and DEPT. Baicalein showed selective inhibitory activity against VHR DS-PTPase with $IC_{50}=2.4\;{\mu}M$, and showed cytotoxicity against several human cancer cell lines with an $GI_{50}$ of $5.26{\sim}12.93\;{\mu}g/mL$ range, including, melanoma (LOX-IMVI), lung cancer (NCI H23 and A549), colon cancer (HCT 116 and SW 620), prostate cancer (PC-3), and leukemia (MOLT 4F).
Lee, Sangjun;Ko, Kwang-Pil;Lee, Jung Eun;Kim, Inah;Jee, Sun Ha;Shin, Aesun;Kweon, Sun-Seog;Shin, Min-Ho;Park, Sangmin;Ryu, Seungho;Yang, Sun Young;Choi, Seung Ho;Kim, Jeongseon;Yi, Sang-Wook;Kang, Daehee;Yoo, Keun-Young;Park, Sue K.
Journal of Preventive Medicine and Public Health
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v.55
no.5
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pp.464-474
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2022
Objectives: We introduced the cohort studies included in the Korean Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies. Methods: We mainly focused on the characteristics of individual cohort studies from the KCC. We developed "PROFAN", a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 1:1 case-control study were also calculated. Results: The KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917-72 102. Conclusions: We propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes.
Substantial evidences have been accumulated about the hormone-like effects of exogenous substances such as pesticides and industrial chemicals during past years. The effects of these substances on the endocrine system are believed to be either enhancing or reducing of various endocrine action. It is necessary to identify putative causal agents by the batter system and to assess their ability to disrupt the endocrine system. A variety of in vitro and In vivo approaches have been used to determine the androgenic effects of environmental chemicals. To establish the method for assessment of the putative endocrine disruptors with androgenic activity, we carried out the cell proliferation assay by MTS method after treatment with the various concentration of testosterone in LNCaP cells (human prostatic cancer cell line) and also observed the expression of androgen-related genes by quantitative RT-PCR. In the cell proliferation assay, the results showed that the grouth of LNCaP cells increased within level of at least 10pM testosterone. We measured by quantitative RT-PCR method on the effects of testosterone on mRNA expression of androgen receptor (AR), prostate-specific antigen (PSA), bone morphogenetic protein (BMP) and BMP receptor (BMPR) In LNCaP cells. The results demonstrated that mRNA expression of PSA and BMPR-IB was observed differently within level of at least 0.01 pM testosterone compared with non-treated control. These observations suggest that the detection of PSA and BMPR-IB mRNA by the quantitative RT-PCR in LNCaP cells is very sensitive method to identify the endocrine disruptors to have the androgenic effects.
Kim, Hee-Su;Kim, Yong-Bin;Choi, Donchan;Cheon, Yong-Pil;Lee, Sung-Ho
Development and Reproduction
/
v.21
no.4
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pp.441-448
/
2017
Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.
Journal of the Korea Academia-Industrial cooperation Society
/
v.12
no.6
/
pp.2660-2667
/
2011
TREK-1 channel is a member of the two-pore domain potassium (K2P) channel family that is regulated by intracellular pH, membrane stretch, polyunsaturated fatty acids, temperature, and some neuroprotectant agents. TREK-1 channel can influence neuronal excitability by regulating leakage of potassium ions and resting membrane potential. TREK-1 channel has been shown to be overexpressed in prostate cancer cells. Although the importance of these properties, relatively little is known about flavonoid effects in the regulations of TREK-1 channel. The purpose of the study was to screening of flavonoids as the TREK-1 channel modulator using one of electrophysiological techniques such as excised inside-out patch configuration. We demonstrated blocking effect on TREK-1 channel by flavonoids such as epigallocatechin-3-gallate (EGCG), curcumin and quercetin in CHO cells transiently expressing TREK-1 channel. The inhibition of TREK-1 channel by quercetin and curcumin was reversible, whereas EGCG was little reversible. Quercetin, EGCG and curcumin decreased the relative channel activity to 73%, 91% and 94%, respectively. The half-inhibitory concentration (IC50) of curcumin, quercetin and EGCG was $1.04{\pm}0.19\;{\mu}M$, $1.13{\pm}0.26\;{\mu}M$ and $13.5{\pm}2.20\;{\mu}M$ in CHO cells expressing TREK-1 channel, respectively. These results indicate that flavonoids might regulate TREK-1 and this regulation might be one of the pharmacological actions of flavonoid in nervous systems and cancer cells.
Kim, Ki-Jun;Sohn, Hyung-Sun;Park, Jeong-Mi;Chung, Soo-Kyo;Lee, Jae-Moon;Kim, Choon-Yul;Bahk, Yong-Whee;Shinn, Kyung-Sub
The Korean Journal of Nuclear Medicine
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v.28
no.3
/
pp.384-390
/
1994
Authors retrospectively compared the 99mTc MDP bone scans and corresponding MR imagings in 20 patients with histologically proven malignancy, Mean interval of the two studies was 16.6 days, Cancer diagnosis Included 8 lung, 2 each of colon, breast, stomach, 1 each of prostate, thyroid, malignant lymphoma and 3 adenocarcinoma of unknown primary site. Of the 105 regions compared, :t6 regions were positive for metastases in bone scans or MR imagings. 30 regions(65.2%) were positive by bone scan and 44 regions(95.7%) by MR imaging. 87 regions(82.9%) were concordantly positive or negative by bone scan and MR imaging, but 18 regions(17.1%) were discordant. In the discordant regions, 16 regions positive in MR imaging were negative in bone scan. The greatest number of discordant findings occured in the cervical region and in the patient with stomach cancer. Our results suggest that the sensitivity of MR Imaging is greater than that of bone scan in detecting spinal metastases. And bone scan is useful screening test of metastasis for evaluating entire skeleton including spine.
Objectives: Sleep disturbance is a very rapidly growing disease with aging. The purpose of this study was to investigate the prevalence of sleep disturbances and its predictive factors in a three-year cohort study of people aged 60 years and over in Korea. Methods: In 2012 and 2014, we obtained data from a survey of the Korean Social Life, Health, and Aging Project. We asked participants if they had been diagnosed with stroke, myocardial infarction, angina pectoris, arthritis, pulmonary tuberculosis, asthma, cataract, glaucoma, hepatitis B, urinary incontinence, prostate hypertrophy, cancer, osteoporosis, hypertension, diabetes, hyperlipidemia, or metabolic syndrome. Cognitive function was assessed using the Mini-Mental State Examination for dementia screening in 2012, and depression was assessed using the Center for Epidemiologic Studies Depression Scale in 2012 and 2014. In 2015, a structured clinical interview for Axis I psychiatric disorders was administered to 235 people, and sleep disturbance was assessed using the Pittsburgh Sleep Quality Index. The perceived stress scale and the State-trait Anger Expression Inventory were also administered. Logistic regression analysis was used to predict sleep disturbance by gender, age, education, depression score, number of coexisting diseases in 2012 and 2014, current anger score, and perceived stress score. Results: Twenty-seven percent of the participants had sleep disturbances. Logistic regression analysis showed that the number of medical diseases three years ago, the depression score one year ago, and the current perceived stress significantly predicted sleep disturbances. Conclusion: Comorbid medical disease three years previous and depressive symptoms evaluated one year previous were predictive of current sleep disturbances. Further studies are needed to determine whether treatment of medical disease and depressive symptoms can improve sleep disturbances.
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