• Title/Summary/Keyword: Preclinical

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Targeted alpha therapy (TAT) for cancer using metallic radioisotopes

  • Kang, Chi Soo;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.2
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    • pp.135-144
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    • 2019
  • Targeted alpha therapy (TAT) based on metallic radionuclides has attracted a lot of attention lately due to its impressive therapeutic efficacy displayed in couple of clinical studies for cancer. Representative metallic radionuclides emitting alpha-particle include 225Ac, 213Bi, and 227Th, and there have been variety of TAT formulations based on different targeting moiety and chelating agents. In this review, we introduce strategies to label metallic radioisotopes with biomolecules and look at some of recent preclinical and clinical results of TAT for cancer.

Comparative Proteome Analysis of Celastrol-Treated Helicobacter pylori

  • Kim, Sa-Hyun
    • Biomedical Science Letters
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    • v.23 no.4
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    • pp.395-401
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    • 2017
  • Various preclinical and clinical trials have been conducted the efficacy of celastrol. In data presented in the current manuscript is the first trial to inhibit Helicobacter pylori with celastrol. In this study, the quantitative change of various H. pylori proteins including CagA and VacA by the anti-bacterial effect of celastrol was determined. The anti-H. pylori effects of celastrol was investigated by performing 2-dimensional electrophoresis and additional supporting experiments. After 2-dimensional electrophoresis analysis, spot intensities were analyzed and then each spot was identified using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) or peptide sequencing using Finnigan LCQ ion trap mass spectrometer (LC-MS/MS). The results show that celastrol has multiple effects on protein expression in H. pylori.

PRECLINICAL TOXICITY STUDY OF A NEW PHOSPHODIESTERASE-5 INHIBITOR (II) FOUR-WEEK SUBACUTE TOXICITY STUDY IN RATS

  • Hyeon Cho;Kim, Dong-Hwan;Kang, Kyung-Koo;Ahn, Byoung-Ok;Kim, Won-Bae
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.128-128
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    • 2001
  • Toxic effects of a new phosphodiesterse-5 inhibitor, DA-8159, were investigated in Sprague-Dawley rats by repeated oral administration. Four groups of 10 male and 10 female rats were treated with DA-8159 at a dose of 0, 40, 80, or 320 mg/kg/day for 4 weeks.(omitted)

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Single Dose Toxicity Studies of STB-HO-BM in Rats and Dogs (게르마늄 복합물 STB-HO-BM의 랫드 및 비글견에서 단회투여 독성연구)

  • Song Si-Whan;Jung Winston;Hong Dong-Ho
    • Toxicological Research
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    • v.22 no.2
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    • pp.153-156
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    • 2006
  • The acute toxicity of STB-HO-BM was evaluated in Sprague Dawley (SS) rats and beagle dogs. STB-HO-BM was administered orally to rats at dose levels of 0 and 2,000mg/kg/day and to dogs at dose levels of 0, 500, 1,000 and 2,000 mg/kg/day. In these experiments, there were no death and clinical changes which were related to STB-HO-BM administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of STB-HO-BM 2,000 mg/kg in SD rats and up to 2,000mg/kg in beagle dogs was proved to be safe, and it is thought that STB-HO-BM may not show any toxicity in its clinical use.

Thirteen-week Repeated-dose Toxicity Studies of STB-HO-BM in Rats (랫드에서 STB-HO-BM에 대한 13주 반복투여 독성연구)

  • Song Si-Whan;Jung Winston;Hong Dong-Ho
    • Toxicological Research
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    • v.22 no.2
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    • pp.135-144
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    • 2006
  • This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.

Current Situation of the International Recognition of Toxicologists -Update of the Japanese Society of Toxicology-

  • Horii, Ikuo
    • Toxicological Research
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    • v.17
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    • pp.193-196
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    • 2001
  • Issuance of certification and licensing for toxicologists authorized by the Japanese Society of Thxicology (JST) became effective on July 24, 1997. The certification system consists of examination, eligibility requirements for the applicants, authorization/license by the board of trustees of JST, and the re-certification of previously authorized qualification. In the last 2-3 years, about 30-40% of candidates for the examination have succeeded. The Committee has estimated that the level of the examination would be sufficient to determine qualified toxicologists. This updated status and a detailed explanation are to be presented at the workshop. In global terms, the JST special committee agrees that "harmonization of certification/registration procedure for qualified toxicologists means to ensure/set the minimum requirement for the global authorization of qualified toxicologists". The following items in global authorization are ad-dressed for further discussion: (1) What's the benefit\ulcorner (2) Toxicological safety assessment standards, and (3) the JST position for authorization.orization.

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CPC-222, A New Fluoroquinolone

  • Lee, Younha
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.12-12
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    • 1997
  • CFC-222 is a novel fluoroqinolone antibacterial agent synthesized and under development by the Cheil Jedang Corporation, Korea. CFC-222 exerts the antibacterial activity by inhibition of bacterial DNA gyrase leading to bactericidal action. In in vitro and in vivo preclinical testing, CFC-222 has been shown to possess a broad spectrum of antibacterial activity. In particular CFC-222 is very potent against Gram-positive bacteria such as Staphylococcus spp., Streptocuccus spp. (in particular penicillin G-resistant and -susceptible S. pneumoniae) and Enterococcus spp. when compared to other quinolones (ciprofloxacin, ofloxacin or lomefloxacin). CFC-222 also showed potent activity against the methicillin resistant clinical isolates of S. aureus (MRSA). Against Gram-negative bacteria (E. coli, Pseudomonas and Sarcina) the activity of CFC-222 was slightly weaker than that of ciprofloxacin, but was more potent than that of ofloxacin or lomefloxacin. In urinary systemic infections caused by both Gram-positive and -negative bacteria, CFC-222 demonstrated a potent therapeutic efficacy in particular against Cram-positive bacteria S. aureus, S. pyrogen 203 and S. pneumonia TypeIII.

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Metabotropic Glutamate Receptor and Anxiety (Metabotropic Glutamate 수용체와 불안)

  • Park, Young-Min;Yi, Hyeon-Lyung;Lee, Seung-Hwan
    • Anxiety and mood
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    • v.3 no.1
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    • pp.8-14
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    • 2007
  • Although treatments of anxiety symptom have been available for decades, the biological basis for anxiety disorders in humans is just beginning to emerge. Recently, there is a growing body of literature suggesting that group II metabotrpic glutamate (mGlu) receptors and group I mGlu receptors are important in the physiological and behavioral sequelae associated with stressful stimuli. Moreover, compounds selective for mGlu receptors, particularly mGlu2/3 and/or mGlu5, have proven as effective as classical anxiolytics in various animal models of anxiety without producing many of the unwanted side effects that are typical of current therapies. This article will focus on the emerging preclinical and clinical data that implicate modulation of the mGlu receptors as a potential anxiolytic strategy.

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Cardiovascular Molecular Imaging (심장 분자영상)

  • Lee, Kyung-Han
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.3
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    • pp.229-239
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    • 2009
  • Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis, Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field.

Molecular Targeting Agents in Cancer Therapy: Science and Society

  • Shaikh, Asim Jamal
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1705-1708
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    • 2012
  • The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.