• Title/Summary/Keyword: Preclinical

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Cancer Chemopreventive Potential of Procyanidin

  • Lee, Yongkyu
    • Toxicological Research
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    • v.33 no.4
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    • pp.273-282
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    • 2017
  • Chemoprevention entails the use of synthetic agents or naturally occurring dietary phytochemicals to prevent cancer development and progression. One promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol that exhibits beneficial health effects including anti-inflammatory, antiproliferative, and antitumor activities. Currently, many preclinical reports suggest procyanidin as a promising lead compound for cancer prevention and treatment. As a potential anticancer agent, procyanidin has been shown to inhibit the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin has numerous targets, many of which are components of intracellular signaling pathways, including proinflammatory mediators, regulators of cell survival and apoptosis, and angiogenic and metastatic mediators, and modulates a set of upstream kinases, transcription factors, and their regulators. Although remarkable progress characterizing the molecular mechanisms and targets underlying the anticancer properties of procyanidin has been made in the past decade, the chemopreventive targets or biomarkers of procyanidin action have not been completely elucidated. This review focuses on the apoptosis and tumor inhibitory effects of procyanidin with respect to its bioavailability.

Metabolomic approach for evaluating drug response

  • Jung, Byung-Hwa
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.11-15
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    • 2007
  • Metabolomics is an emerging technology which makes it possible to evaluate change of biological system in response to the physiological, environmental alterations. It has advantages in the simplicity and sensitivity to analyze metabolites since the researcher can use cutting edge instrument, such as mass spectrometry and simple sample preparation method compared to genomics or proteomics. Nowadays this technology has been tried in pharmaceutical area to investigate toxicity and efficacy of drug candidates and drugs in preclinical test. The metabolomic applications on the pharmaceutics for early prediction on toxicity and efficacy are described in this presentation. The multivariate analysis to get metabolic fingerprinting and its relations with the physiological changes are investigated with several drugs. Feasibility of metabolomic application for pharmaceutical area would be suggested from those researches.

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Radioimmunotherapy (I): Development of Radioimmunoconjugates (방사면역치료(I): 방사면역접합체 개발)

  • Choi, Tae-Hyun;Lim, Sang-Moo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.66-73
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    • 2006
  • Monoclonal antibodies are designed to bind specifically to certain antigen, give therapeutic effect to the target and to be produced in large scale with homogeneity. The monoclonal antibodies conjugated with radionuclide can deliver therapeutic irradiation to the target, and showed successful results in certain malignancies, which is known as radioimmunotherapy. The target-to-background ratio depends on the antigen expression in the target and normal tissues, which is related to the therapeutic efficacy and toxicity in radioimmunotherapy. For the solid tumor beta-ray energy should be high, but lower beta energy is better for the hematological malignancies. I-l31 is widely used in thyroid cancer with low cost and high availability. Labeling monoclonal antibody with I-131 is relatively simple and reproducible. Some preclinical data for the I-131 labeled monoclonal antibodies including acute toxicity and efficacy are available from already published literatures in KIRAMS, physician sponsored clinical trial protocols using Rituximab, KFDA approved anti-CD20 chimeric monoclonal antibody and I-131 were approved by KFDA and currently are ongoing.

Mucin in cancer: a stealth cloak for cancer cells

  • Wi, Dong-Han;Cha, Jong-Ho;Jung, Youn-Sang
    • BMB Reports
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    • v.54 no.7
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    • pp.344-355
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    • 2021
  • Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this mini-review, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma.

Mouse models of breast cancer in preclinical research

  • Park, Mi Kyung;Lee, Chang Hoon;Lee, Ho
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.160-165
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    • 2018
  • Breast cancer remains the second leading cause of cancer death among woman, worldwide, despite advances in identifying novel targeted therapies and the development of treating strategies. Classification of clinical subtypes (ER+, PR+, HER2+, and TNBC (Triple-negative)) increases the complexity of breast cancers, which thus necessitates further investigation. Mouse models used in breast cancer research provide an essential approach to examine the mechanisms and genetic pathway in cancer progression and metastasis and to develop and evaluate clinical therapeutics. In this review, we summarize tumor transplantation models and genetically engineered mouse models (GEMMs) of breast cancer and their applications in the field of human breast cancer research and anti-cancer drug development. These models may help to improve the knowledge of underlying mechanisms and genetic pathways, as well as creating approaches for modeling clinical tumor subtypes, and developing innovative cancer therapy.

Update of early phase clinical trials in cancer immunotherapy

  • Lee, Dae Ho
    • BMB Reports
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    • v.54 no.1
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    • pp.70-88
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    • 2021
  • Immunotherapy has revolutionized the landscape of cancer treatment and become a standard pillar of the treatment. The two main drivers, immune checkpoint inhibitors and chimeric antigen receptor T cells, contributed to this unprecedented success. However, despite the striking clinical improvements, most patients still suffer from disease progression because of the evolution of primary or acquired resistance. This mini-review summarizes new treatment options including novel targets and interesting combinational approaches to increase our understanding of the mechanisms of the action of and resistance to immunotherapy, to expand our knowledge of advances in biomarker and therapeutics development, and to help to find the most appropriate option or a way of overcoming the resistance for cancer patients.

Food application of enzymes derived from microorganisms degrading chitin and chitosan (키틴과 키토산 분해 미생물 유래 효소의 식품에의 이용)

  • Park, Jae Kweon
    • Food Science and Industry
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    • v.53 no.1
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    • pp.43-55
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    • 2020
  • Most reports demonstrated the substrate specificity-based kinetic properties of chitin or chitosan degrading enzymes. However, there is virtually less information on the high quality and quantity production of chitin or chitosan hydrolysates having a larger than (GlcN)7 from the hydrolysis of high molecular weight chitosan using specific enzymes and their biological activity. Therefore, the production of such molecules and the discovery of such enzyme sources are very important. Fortunately, the author has established a mass production method of chitosan hydrolysates (GlcN)n, n=2-13 that have been characterized as a potent antioxidant substance, as well as antifungal and antibacterial activities against Penicillium species and highly selective pathogenic bacteria. In addition, preclinical studies using (GlcN)n, n=5-25 demonstrated that these molecules played a very important role in maintaining biometric balance. Collectively, it is implicated that the application of these mixed substances to foods with significant biological activity is very encouraging.

Synthesis ot Brefeldin A Lactam Analogue

  • Paek, Seung-Mann;Seo, Seung-Yong;Jung, Jae-Kyung;Han, Young-Taek;Seo, Young-Ger
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.245.2-245.2
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    • 2003
  • (+)-Brefeldin A (1) has been, since its isolation1 and structural elucidation2 many years ago, one of the most attractive targets for synthetic chemists due to its wide range of biological activities and well-functionalized macrolide structure. Its biological mode of action has been disclosed by a number of important discoveries. Especially the ability of brefeldin A to induce DNA fragmentation associated with apoptosis in cancer cells has stimulated a great deal of recent interest in its preclinical development as an anticancer agent. (omitted)

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Immunodulatory activity of betulinic acid from Lycopus lucidus in murine macrophage RAW 264.7 cells

  • Yun, Yun-Ha;Song, Young-Chun;Son, Han-Shik;Yim, Dong-Sool;Lee, Soo-Kyeon;Kim, Kyung-Jae
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.130.2-130.2
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    • 2003
  • Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human tumor cells. It also exhibits anti-inflammatory and immunomodulatory properties. Due to its high level of these activities and lack of toxicity, BA is an attractive and promising compound as a new drug and recently undergoing preclinical development as an immunomodulators. How BA mediates these matters is not known yet. (omitted)

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The Pharmacological Properties of Silymarin and Its Constituents

  • Antika, Lucia Dwi;Dewi, Rita Marleta
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.68-77
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    • 2021
  • Silymarin is a standardized extract obtained from the seeds and fruits of Silybum marianum L., or commonly called milk thistle, a member of Carduus marianum family that contains mix of flavonolignans. Some epidemiological and preclinical studies revealed that S. marianum L. has been used for herbal remedies for centuries for its pharmacological activity. In this review, pharmacological studies in vitro and in vivo of silymarin are discussed thoroughly stressing on antioxidant, antimicrobial, antiviral, and anti-carcinogenic aspects of silymarin. In addition, the protective influences of silymarin on some organs such as heart, liver, bone, and neuron tissue are reviewed as well. This review would be useful for further study regarding the potential of natural plant, notably silymarin, and its therapeutic potential in the prevention and treatment of diseases.