• Title/Summary/Keyword: Genetic screening

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Screening of novel alkaloid inhibitors for vascular endothelial growth factor in cancer cells: an integrated computational approach

  • Shahik, Shah Md.;Salauddin, Asma;Hossain, Md. Shakhawat;Noyon, Sajjad Hossain;Moin, Abu Tayab;Mizan, Shagufta;Raza, Md. Thosif
    • Genomics & Informatics
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    • v.19 no.1
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    • pp.6.1-6.10
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    • 2021
  • Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

A Fundamental Genetic Study for Identifying Band 3 and CHS Genetic Diseases in Korean Cattle (Hanwoo) (한우 Band 3 및 CHS 유전병의 분자유전학적 기초연구)

  • Chung, Haeng-Jin;Yu, Seong-Lan;Sang, Byung-Chan;Lee, Jun-Heon
    • Korean Journal of Agricultural Science
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    • v.32 no.1
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    • pp.53-61
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    • 2005
  • Many bovine genetic diseases are currently unidentified in Korea because of the relatively low monitoring systems in the livestock farms. The molecular detection system using PCR-RFLP of two genetic diseases, namely Band 3 (Erythrocyte Membrane Protein Band III) and CHS (Chediak-Higashi Syndrome), have been identified in Japan and used for screening large number of cattle whether each individual has the genetic disease or not. Using the 22 unrelated Korean cattle (Hanwoo) individuals, molecular detection system based on PCR-RFLP have been investigated, which can be distinguishable carriers for the genetic diseases. Even though we could not found the causative mutations for two genetic diseases, the PCR-RFLP techniques used in this study are very valuable for the screening the genetics diseases in Korean cattle, especially for the proven or candidate bulls.

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Reviewing Articles Related to Recent Advances in Non-invasive Prenatal Testing and Nursing Implications (최신 비침습적 산전 유전 검사(NIPT)의 임상 적용과 간호학적 의미)

  • Jun, Myunghee;Shin, Gyeyoung;Hur, Myung Haeng;Choi, Kyung-Sook
    • The Journal of Korean Academic Society of Nursing Education
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    • v.19 no.4
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    • pp.675-683
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    • 2013
  • Purpose: Nineteen articles were analyzed to gather opinions and nursing implications about NIPT recently launched. Methods: Nineteen articles were selected from EBSCO (eBook business collection), Google Scholar, and two Korean academic d-bases with key words 'prenatal screening testing', 'prenatal genetic diagnostic testing', NIPT or 'cell free DNA (cfDNA)'. Authors developed a framework for analyzing the 19 articles including opinions and suggestions for future implications. Results: Eleven articles written by the first author affiliated with medicine or genetics, viewed NIPT as promising because of safety, accuracy, early detectability and cost effectiveness. Articles written by journalists or authors affiliated with history and ethics were concerned with the possible risk of ELSI (ethical, legal, social issues), erratic interpretation of test results, and lack of genetic counseling service. Conclusion: With consideration of Korean clinical, and legal circumstances, not only pregnant women and families but also health professionals must prepare for clinical NIPT implications including updating prenatal genetic testing, counseling services, protecting ELSI and amulticultural team approach.

Hereditary cancer and genetic counseling (유전성 암과 유전상담)

  • Jeong, Seung-Yong
    • Journal of Genetic Medicine
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    • v.4 no.1
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    • pp.15-21
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    • 2007
  • Hereditary syndromes cause approximately 5 to 10% of overall cancer cases. Cancer related with genetic syndromes are found elsewhere, including stomach, breast, colorectum, ovary, brain and so on. Because hereditary cancers are due to germline mutations, these patients have unique clinical features distinct from sporadic cancer. Generally these features include (i) early age-of onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent bilateral involvement in paired organs (iv) frequent association with other site tumors or characteristic clinical manifestation specific to each genetic syndrome. Due to these differences, the management strategy for patients with hereditary cancer is quite different from that for sporadic cancer. Additionally, there are important screening and surveillance implications for family members. Genetic counselling is prerequisite to these families for risk assessment by pedigree analysis, and guidance to clinical or genetic testing. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become important determining factor in clinical decisions.

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Genetic testing in clinical pediatric practice

  • Yoo, Han Wook
    • Clinical and Experimental Pediatrics
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    • v.53 no.3
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    • pp.273-285
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    • 2010
  • Completion of the human genome project has allowed a deeper understanding of molecular pathophysiology and has provided invaluable genomic information for the diagnosis of genetic disorders. Advent of new technologies has lead to an explosion in genetic testing. However, this overwhelming stream of genetic information often misleads physicians and patients into a misguided faith in the power of genetic testing. Moreover, genetic testing raises a number of ethical, legal, and social issues. Diagnostic genetic tests can be divided into three primary but overlapping categories: cytogenetic studies (including routine karyotyping, high-resolution karyotyping, and fluorescent in situ hybridization studies), biochemical tests, and DNA-based diagnostic tests. DNA-based testing has grown rapidly over the past decade and includes preandpostnatal testing for the diagnosis of genetic diseases, testing for carriers of genetic diseases, genetic testing for susceptibility to common non-genetic diseases, and screening for common genetic diseases in a particular population. Theoretically, once a gene's structure, function, and association with a disease are well established, the clinical application of genetic testing should be feasible. However, for routine applications in a clinical setting, such tests must satisfy a number of criteria. These criteria include an acceptable degree of clinical and analytical validity, support of a quality assurance program, possibility of modifying the course of the diagnosed disease with treatment, inclusion of pre-and postnatal genetic counseling, and determination of whether the proposed test satisfies cost-benefit criteria and should replace or complement traditional tests. In the near future, the application of genetic testing to common diseases is expected to expand and will likely be extended to include individual pharmacogenetic assessments.

Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

  • Kobet, Robert A.;Pan, Xiaoping;Zhang, Baohong;Pak, Stephen C.;Asch, Adam S.;Lee, Myon-Hee
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.371-383
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    • 2014
  • 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.

Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach

  • Habib, Abdul Musaweer;Islam, Md. Saiful;Sohel, Md.;Mazumder, Md. Habibul Hasan;Sikder, Mohd. Omar Faruk;Shahik, Shah Md.
    • Genomics & Informatics
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    • v.14 no.4
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    • pp.255-264
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    • 2016
  • The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

Molecular Genetic Analysis of Leaf Senescence in Arabidopsis

  • Woo, Hye-Ryun;Lee, Ung;Cho, Sung-Whan;Lim, Pyung-Ok;Nam, Hong-Gil
    • Korean Journal of Plant Tissue Culture
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    • v.27 no.4
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    • pp.259-268
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    • 2000
  • Senescence is a sequence of biochemical and physiological events that lead to death of a cell, organ, or whole organism. Senescence is now clearly regarded as a genetically determined and evolutionarilly acquired developmental process comprising the final stage of development. However, in spite of the biological and practical importance, genetic mechanism of senescence has been very limited. Through forward and reverse genetic approaches, we are trying to reveal the molecular and genetic mechanism of senescence in plants, employing leaf organs of Arabidopsis as a model system. Using forward genetic approach, we have initially isolated several delayed senescence mutants either from T-DNA insertional lines or chemical-mutagenized lines. In the case of ore 4 and ore 9 mutants, the mutated genes were identified. The recent progress on characterization of mutants and identification of the mutated genes will be reported. We are also screening mutations from other various sources of mutant pools, such as activation tagging lines and promoter trap lines. Two dominant senescence-delayed mutants were isolated from the activation tagging pool. Cloning of the genes responsible for this phenotype is in progress. For reverse genetic approach, the genes that induced during leaf senescence were first isolated by differential screening method. We are currently using PCR-based suppression subtractive hybridization, designed to enrich a cDNA library for rare differentially expressed transcripts. Using this method, we have identified over 35 new sequences that are upregulated at leaf senescence stage. We are investigating the function of these novel genes by systemically generating antisense lines.

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