• Title/Summary/Keyword: Therapeutic candidate

Search Result 275, Processing Time 0.026 seconds

Microarray and Next-Generation Sequencing to Analyse Gastric Cancer

  • Dang, Yuan;Wang, Ying-Chao;Huang, Qiao-Jia
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.19
    • /
    • pp.8035-8040
    • /
    • 2014
  • Gastric cancer is the second after lung cause of cancer-related mortality in the world. Early detection and treatment can lead to a long survival time. Recently microarrays and next generation sequencing (NGS) have become very useful tools of comprehensive research into gastric cancer, facilitating the identification of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discovery to practical clinical benefits. Although there are many biomarkers and target agents, only a minority of patients are tested and treated accordingly. Microarray technology with maturity was established more than 10 years ago, and has been widely used in the study of functional genomics, systems biology, and genomes in medicine. Second generation sequencing technology is more recent, but development is very fast, and it has been applied to the genome, including sequencing and epigenetics and many aspects of functional genomics. Here we review insights gained from these studies regarding the technology of microarray and NGS, how to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets, and how to analyse candidate genes. We also discuss the challenges and future directions of such efforts.

Cell proliferation effect of brown marine algae extracts on Mouse Fibroblast (해조류 추출물이 섬유아세포의 증식에 미치는 영향)

  • Ko, Ju-Young;Lee, Ji-Hyeok;Kim, Hyun-Soo;Kim, Hyung-Ho;Jeon, You-Jin
    • Journal of Marine Bioscience and Biotechnology
    • /
    • v.7 no.1
    • /
    • pp.28-34
    • /
    • 2015
  • We examined cell regeneration efficiency of brown marine algae living in Jeju coast for search of a novel therapeutic device with cutaneous wound healing materials. The five algae were collected and compared with epidermal growth factor (EGF) as a positive control in the assays of cell proliferation and cell migration of NIH3T3 fibroblast cells. Among the 80% methanol extracts of these brown algae, the two algal extracts from Ishige foliacea and Colpomenia bullosa showed the proliferative effects of the cells similar to the effect of EGF. Besides it was found that Colpomenia bullosa extract significantly enhanced cell migration of NIH3T3 cell. In the study, therefore, we confirmed that the Colpomenia bullosa extract improved proliferation of NIH3T3 cell and a potential candidate for cultaneous wound healing.

Dopamine Transporter Gene Polymorphism in ADHD (주의력결핍 과잉운동장애에서 도파민 수송체 유전자 다형성)

  • Shin, Dongwon
    • Korean Journal of Biological Psychiatry
    • /
    • v.9 no.1
    • /
    • pp.8-14
    • /
    • 2002
  • Patients with attention deficit hyperactivity disorder(ADHD) have symptoms of inattention, hyperactivity, impulsivity. Symptoms of ADHD are responsive to medications such as methylphenidate, dextroamphetamine, pemoline, and bupropion. The functional change of the dopamine transporter is related to the therapeutic effect of these drugs. This can be one reason for the dopamine transporter to be emphasized in the research field of ADHD. ADHD has a genetic tendency. Since dopamine transporter gene(DAT1) knock out mice were reported to be several times more active than normal mice in a novel situation, lights has been shed on DAT1 as a candidate gene for ADHD. Though there have been several studies which reported an association between DAT1 and ADHD, the association between DAT1 and ADHD is not conclusive. Since Vandenbergh reported the DAT1 polymorphism with variable number of tandem repeats(VNTR), and the racial differences in allelic frequencies of the DAT1, wide ethnic variation in the distribution of the DAT1 polymorphism had been confirmed. Wide ethnic variation in the distribution of the DAT1 suggested that there might be ethnic difference in the association between DAT1 and ADHD. Before applying previous findings to Koreans, verification might be needed for Korean patients with ADHD.

  • PDF

Anti-proliferative Effects of Bee Venom through Induction of Bax and Cdk Inhibitor p21WAF1/CIP1 in Human Lung Carcinoma Cells (Bax 및 Cdk inhibitor p21WAF1/CIP1 발현 증가에 의한 bee venom의 A549 인체폐암세포 성장억제)

  • Choi, Yung-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.19 no.1
    • /
    • pp.167-173
    • /
    • 2005
  • To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

Falcarindiol from Angelica koreana Down-regulated IL-8 and Up-regulated IL-10 in Colon Epithelial Cells

  • Shim, Sun-Yup;Lee, Seul-gi;Kim, Mihye;Lee, Jin Woo;Hwang, Bang Yeon;Lee, Mina
    • Natural Product Sciences
    • /
    • v.23 no.2
    • /
    • pp.103-107
    • /
    • 2017
  • Angelica koreana is an important medicinal plant for some locals in East Asia including Korea. A few reports have shown the efficacy of its phytochemical constituents. We have isolated and purified one compound falcarindiol (FAL) from the methanolic extract of A. koreana roots. At concentrations from to $1{\mu}M$ to $25{\mu}M$, the FAL isolated from the roots of A. koreana exerted no significant cytotoxicity and down-regulated LPS-stimulated pro-inflammatory cytokine IL-8 in colon epithelial cells, while up-regulating anti-inflammatory cytokine IL-10. In addition, the FAL decreased the expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein by Western blot analysis. Colon epithelial cells play pivotal roles in regulating the colon immune system and thus FAL is expected to be candidate agent as therapeutic potential for the treatment of inflammatory bowel disease (IBD) by modulating LPS-induced inflammation in colon epithelial cells.

Structure-Activity Relationship of the N-terminal Helix Analog of Papiliocin, PapN

  • Jeon, Dasom;Jeong, Min-Cheol;Kim, Jin-Kyoung;Jeong, Ki-Woong;Ko, Yoon-Joo;Kim, Yangmee
    • Journal of the Korean Magnetic Resonance Society
    • /
    • v.19 no.2
    • /
    • pp.54-60
    • /
    • 2015
  • Papiliocin, from the swallowtail butterfly, Papilio xuthus, shows high bacterial cell selectivity against Gram-negative bacteria. Recently, we designed a 22mer analog with N-terminal helix from $Lys^3$ to $Ala^{22}$, PapN. It shows outstanding antimicrobial activity against Gram-negative bacteria with low toxicity against mammalian cells. In this study, we determined the 3-D structure of PapN in 300 mM DPC micelle using NMR spectroscopy and investigated the interactions between PapN and DPC micelles. The results showed that PapN has an amphipathic ${\alpha}$-helical structure from $Lys^3$ to $Lys^{21}$. STD-NMR and DOSY experiment showed that this helix is important in binding to the bacterial cell membrane. Furthermore, we tested antibacterial activities of PapN in the presence of salt for therapeutic application. PapN was calcium- and magnesium-resistant in a physiological condition, especially against Gram-negative bacteria, implying that it can be a potent candidate as peptide antibiotics.

Anticancer Effect of Paedoksans for Oral Squamous Cell Carcinoma and Malignant Pleural Mesothelioma (패독산류의 구강편평세포암종 및 악성중피종에 대한 항암 활성)

  • Oh, Ha-Na;Kim, Hyun-Jung;Chae, Jung-Il;Shim, Jung-Hyun;Yoon, Goo
    • Korean Journal of Pharmacognosy
    • /
    • v.48 no.3
    • /
    • pp.213-218
    • /
    • 2017
  • In order to search for anticancer agent as therapy of oral squamous cell carcinoma (OSCC) and malignant pleural mesothelioma (MPM) from Korean traditional prescriptions, we selected 58 traditional prescriptions based on a review of the Korean traditional medicine books. Among the selected traditional prescriptions, only water extracts of paedoksan (敗毒散) showed relatively good cytotoxicity at the concentration of $50{\mu}g/ml$. Additionally, we evaluated cytotoxicity for various paedoksans and each herbal ingredient in paedoksans. The root of Anthriscus sylvestris exhibited more cytotoxic effect than any other ingredients in paedoksans. Bioactivity-guided fractionation of the MC layer of Anthriscus sylvestris led to the isolation of deoxypodophyllotoxin (DPT). DPT exhibited dose-dependently significant cytotoxicity against OSCC and MPM cell with nM range. Therefore, DPT from A. sylvestris might be a potential candidate as an effective anticancer therapeutic agent for OSCC and MPM.

XRP44X Enhances the Cytotoxic Activity of Natural Killer Cells by Activating the c-JUN N-Terminal Kinase Signaling Pathway

  • Kim, Kwang-Soo;Park, Kyung-Soon
    • Development and Reproduction
    • /
    • v.24 no.1
    • /
    • pp.53-62
    • /
    • 2020
  • Natural killer (NK) cells are innate lymphocytes that play an essential role in preventing cancer development by performing immune surveillance to eradicate abnormal cells. Since ex vivo expanded NK cells have cytotoxic activity against various cancers, including breast cancers, their clinical potential as immune-oncogenic therapeutics has been widely investigated. Here, we report that the pyrazole chemical XRP44X, an inhibitor of Ras/ERK activation of ELK3, stimulates NK-92MI cells to enhance cytotoxic activity against breast cancer cells. Under XRP44X stimulation, NK cells did not show notable apoptosis or impaired cell cycle progression. We demonstrated that XRP44X enhanced interferon gamma expression in NK-92MI cells. We also elucidated that potentiation of the cytotoxic activity of NK-92MI cells by XRP44X is induced by activation of the c-JUN N-terminal kinase (JNK) signaling pathway. Our data provide insight into the evaluation of XRP44X as an immune stimulant and that XRP44X is a potential candidate compound for the therapeutic development of NK cells.

CR389, a Benzoimidazolyl Pyridinone Analog, Induces Cell Cycle Arrest and Apoptosis via p53 Activation in Human Ovarian Cancer PA-1 Cells

  • Suh, Hyewon;Choi, Ko-woon;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
    • /
    • v.25 no.3
    • /
    • pp.418-422
    • /
    • 2015
  • In the course of screening for novel cell cycle inhibitors and apoptotic inducers, CR389, elucidated as 5-(1H-benzoimidazol-2-yl)-1H-pyridin-2-one, was generated as a new hit compound. Flow cytometric analysis and western blots of PA-1 cells treated with $60{\mu}M$ CR389 revealed an appreciable cell cycle arrest at the G2/M phase through direct inhibition of the CDK1 complex. In addition, activation of p53 via phosphorylation at Ser15 and subsequent up-regulation of p21CIP1 showed that CR389 also induces p53-dependent-p21CIP1-mediated cell cycle arrest. Furthermore, apoptotic induction in $60{\mu}M$ CR389-treated PA-1 cells is associated with the release of cytochrome c from mitochondria through up-regulation of the proapoptotic Bax protein, which results in the activation of procaspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, CR389 seems to have multiple mechanisms of antiproliferative activity through p53-mediated pathways against human ovarian cancer cells. Therefore, we conclude that CR389 is a candidate therapeutic agent for the treatment of human ovarian cancer via the activation of p53.

Anti-Metastasis Effects of Ginsenoside Rg3 in B16F10 Cells

  • Lee, Seul Gi;Kang, Young Jin;Nam, Ju-Ock
    • Journal of Microbiology and Biotechnology
    • /
    • v.25 no.12
    • /
    • pp.1997-2006
    • /
    • 2015
  • Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.