• Title/Summary/Keyword: Lung Cancer Screening

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Suppressor of Variegation 3-9 Homolog 2, a Novel Binding Protein of Translationally Controlled Tumor Protein, Regulates Cancer Cell Proliferation

  • Kim, A-Reum;Sung, Jee Young;Rho, Seung Bae;Kim, Yong-Nyun;Yoon, Kyungsil
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.231-239
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    • 2019
  • Suppressor of Variegation 3-9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing $G_1$ cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120-172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.

Screening of Anti-oxidants Isolated from Natural Products on V79-4 Hamster Lung Fibroblast Cells Induced by Oxidative Stress (산화적 스트레스로 유도된 V79-4 햄스터 폐 섬유아세포에 대한 천연물 분리 항 산화물질 탐색)

  • Kang, Kyoung-Ah;Jo, Su-Hyun;Koh, Young-Sang;Kim, Jin-Sook;Hyun, Jin-Won
    • Korean Journal of Pharmacognosy
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    • v.36 no.1 s.140
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    • pp.34-37
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    • 2005
  • Reactive oxygen species (ROS) are known to cause oxidative modification of DNA, proteins, lipids and small cellular molecules and are associated with tissue damage and are the contributing factors for inflammation, aging, cancer, arteriosclerosis, hypertension and diabetes. We screened the anti-oxidants in V79-4 hamster lung fibroblast cells induced by hydrogen peroxide with eighteen pure compounds isolated from natural products. Allantoin, brassicasterol, and hypaconitine were found to strongly scavenge intracellular reactive oxygen species, which is measured by dichlorodihydrofluorescin diacetate method (DCHF-DA), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical.

Analysis of CEA Expression and EGFR Mutation Status in Non-small Cell Lung Cancers

  • Yang, Zhong-Ming;Ding, Xian-Ping;Pen, Lei;Mei, Lin;Liu, Ting
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3451-3455
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    • 2014
  • Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.

Studies on Anti-cancerous Substances from Higher Plane in East Asian Region

  • Takeya, Koichi
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 1999.10a
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    • pp.1-45
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    • 1999
  • To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for ncancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically Oridonin isolated from Rabdosia ssp.is now investigated for clinical trials in China. Moreover, camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity. This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifolia, has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential. Some efforts are continued in National Cancer Institute NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin III, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected in Japan, China, Korea, Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells in our laboratory, as primary screening. In this meeting, I will present on antitumor and cytotoxic substances of the higher plants (Rubia cordifolia, Ailanfhus Vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var drupacea, etc.) selected from above screening tests.

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Study of Lung Cancer Screening in Health Examination (건강검진에서 폐암검진의 대한 연구)

  • You, In Gyu;Lim, Cheong Hwan
    • Proceedings of the Korea Contents Association Conference
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    • 2014.11a
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    • pp.199-200
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    • 2014
  • 저선량 흉부 전산화단층촬영을 이용한 페암의 대한 조기검진 시기도 남녀공통 40세 이상을 시작연령으로 제시하고 있으나 조기검진의 연령확대로 인하여 다양한 연령층에서 시행하고 있다. 이에 본 연구에서는 임상적 증상이 없는 자기결정에 의해 저선량 흉부 전산화단층촬영을 시행한 건강검진 대상자를 대상으로 40세 전후로 구분하여 진단적 효용성과 저선량 흉부 전산화 단층촬영의 대한 바람직한 방향을 제시하고자 한다. 분석한 결과 결절의 개수는 유의하게 나타났으나 방사선 피폭에 대한 전체적인 위해와 이득에 대한 정당성 확보가 이루어지지 않았다. 저선량 흉부 전산화단층촬영 정당성 확보를 위해 흡연력 있는 40대 이상을 시작연령으로 해야 한다.

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Screening of angiogenesis inhibitors from Korean plants (I) (한국산 식물자원으로부터 신생혈관 억제제 검색 (I))

  • You, Young-Jae;Park, Jin-Young;An, Ren-Bo;Kim, Young-Ho;Kang, Jong-Seong;Ahn, Byung-Zun;Bae, Ki-Hwan
    • Korean Journal of Pharmacognosy
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    • v.31 no.3
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    • pp.320-324
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    • 2000
  • Methanol extracts of 94 Korean plants were screened for angiogenesis inhibitors using the tube-like formation assay of HUVEC (Human Umbilical Vein Endothelial Cell) and evaluated for growth inhibitory activity on A549 cells, human lung cancer cells. Extracts of Euphorbia sieboldiana, Adonis amurensis, and Anthriscus sylvestris showed antiangiogenic and growth inhibitory activity at $50\;{mu}g/ml$. Aristolochia manshuriens and Styrax obassia expressed antiangiogenic activity without growth inhibitory action.

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Identification of inhibitors against ROS1 targeting NSCLC by In- Silico approach

  • Bavya, Chandrasekhar
    • Journal of Integrative Natural Science
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    • v.15 no.4
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    • pp.171-177
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    • 2022
  • ROS1 (c-ros oncogene) is one of the gene with mutation in NSCLC (non-small cell lung cancer). The increased expression of ROS1 is leading to the increase proliferation of cell, cell migration and survival. Crizotinib and Entrectinib are the drugs that have been approved by FDA against ROS1 protein, but recently patients started to develop resistance against Crizotinib and there is a need of new drug that could act as an effective drug against ROS1 for NSCLC. In this study, we have performed virtual screening, where compounds are taken from Zinc 15 dataset and molecular docking was performed. The top compounds were taken based upon their binding affinity and their interactions with the residues. The compounds stability and chemical reactivity was also studied through Density Functional theory and their properties. Further study of these compounds could reveal the required information of ROS1-inhibitor complex and in the discovery of potent inhibitors.

Cytotoxicity Assessment of Six Different Extracts of Abelia triflora leaves on A-549 Human Lung Adenocarcinoma Cells

  • Al-Taweel, Areej Mohammad;Perveen, Shagufta;Fawzy, Ghada Ahmed;Ibrahim, Taghreed Abdou;Khan, Afsar;Mehmood, Rashad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4641-4645
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    • 2015
  • The present investigation was designed to assess the anticancer activity of six different leaf extracts (ethyl acetate, methanol, chloroform, petroleum ether, n-butanol, and water soluble) of Abelia triflora on A-549 human lung adenocarcinoma epithelial cells. A-549 cells were exposed to $10-1000{\mu}g/ml$ concentrations of the leaf extracts of A. triflorafor 24 h and then percentage cell viability was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay. The results showed that leaf extracts of A. triflora significantly reduced the viability of A-549 cells in a concentration-dependent manner. Decrease was recorded as 31% with ethyl acetate, 36% with methanol, 46% with chloroform, 54% with petroleum ether, 62% with n-butanol, and 63% with water soluble extracts at $1000{\mu}g/ml$ each. Among the various plant extracts, ethyl acetate extract showed the highest decrease in the percentage cell viability, followed by methanol, chloroform, petroleum ether, n-butanol, and water soluble extracts. Our results demonstrated preliminary screening of anticancer activity of different soluble extracts of A. triflora extracts against A-549 cells, which can be further used for the development of a potential therapeutic anticancer agents.

Cytotoxic Effect of Aromatic and Aliphatic Compounds Produced by Streptomyces sp. Isolated in Korea (한국 Streptomyces SP.로부터 분리한 방향족 화합물과 지질 화합물의 세포독성 연구)

  • Shin, Suck-Woo;Ryeom, Kon
    • Biomolecules & Therapeutics
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    • v.5 no.2
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    • pp.215-221
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    • 1997
  • In an effort to screen new selective antitumor agents from the broth of soil microorganism, cytotoxicity oriented screening was performed against tumor cells and 3 compounds (Compound 1, 2 and 3) were isolated from Sreptomyces parvullus ISP 5048 and their chemical structures were determined. Among these compounds, Compound 2 showed the highest cytotoxicity against P388Dl and L1210. While the $IC_{50}$/ values of compound 2 against P388Dl and L1210 were 0.073$\mu$g/ml and 0.07$\mu$g/ml, respectively, and the $IC_{50}$/ value of Compound 3 was 0.17$\mu$g/ml against human lung cancer cells, A549, the cytotoxicity of Compound 2 and 3 against normal cell line, Vero E6 cell was about 4- and 8-fold lower than that of adriamycin. Based on the chemical analysis data, Compound 3 was octacosamicine A, a known antibiotic, which was reported by Dobasih et al. (1988). Taken together the results demonstrated that Compound 2 and Compound 3 has the possibility to be developed as antitumor agent because of its potent cytotoxicity as well as high selectivity against various cancer cell lines.

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Projection of Burden of Cancer Mortality for India, 2011-2026

  • Dsouza, Neevan D.R.;Murthy, N.S.;Aras, R.Y.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4387-4392
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    • 2013
  • Projection of load of cancer mortality helps in quantifying the burden of cancer and is essential for planning cancer control activities. As per our knowledge, there have not been many attempts to project the cancer mortality burden at the country level in India mainly due to lack of data on cancer mortality at the national and state level. This is an attempt to understand the magnitude of cancer mortality problem for the various calendar years from 2011 to 2026 at 5-yearly intervals. Age, sex and site-wise specific cancer mortality data along with populations covered by the registries were obtained from the report of National Cancer Registry Programme published by Indian Council of Medical Research for the period 2001-2004. Pooled age sex specific cancer mortality rates were obtained by taking weighted average of these six registries with respective registry populations as weights. The pooled mortality rates were assumed to represent the country's mortality rates. Populations of the country according to age and sex exposed to the risk of cancer mortality in different calendar years were obtained from the report of Registrar General of India providing population projections for the country for the years from 2011 to 2026. Population forecasts were combined with the pooled mortality rates to estimate the projected number of cancer mortality cases by age, sex and site of cancer at various 5-yearly periods Viz. 2011, 2016, 2021 and 2026. The projections were carried out for the various cancer-leading sites as well as for 'all sites' of cancer. The results revealed that an estimated 0.44 million died due to cancer during the year 2011, while 0.51 million and 0.60 million persons are likely to die from cancer in 2016 and 2021. In the year 2011 male mortality was estimated to be 0.23 million and female mortality to be 0.20 million. The estimated cancer mortality would increase to 0.70 million by the year 2026 as a result of change in size and composition of population. In males increase will be to 0.38 millions and in females to 0.32 millions. Among women, cancer of the breast, cervical and ovary account for 34 percent of all cancer deaths. The leading sites of cancer mortality in males are lung, oesophagus, prostrate and stomach. The above results show a need for commitment for tackling cancer by reducing risk factors and strengthening the existing screening and treatment facilities.