• 제목/요약/키워드: Preclinical research

검색결과 242건 처리시간 0.022초

Development of Drugs and Technology for Radiation Theragnosis

  • Jeong, Hwan-Jeong;Lee, Byung Chul;Ahn, Byeong-Cheol;Kang, Keon Wook
    • Nuclear Engineering and Technology
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    • 제48권3호
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    • pp.597-607
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    • 2016
  • Personalized medicine is tailored medical treatment that targets the individual characteristics of each patient. Theragnosis, combining diagnosis and therapy, plays an important role in selecting appropriate patients. Noninvasive in vivo imaging can trace small molecules, antibodies, peptides, nanoparticles, and cells in the body. Recently, imaging methods have been able to reveal molecular events in cells and tissues. Molecular imaging is useful not only for clinical studies but also for developing new drugs and new treatment modalities. Preclinical and early clinical molecular imaging shows biodistribution, pharmacokinetics, mechanisms of action, and efficacy. When therapeutic materials are labeled using radioisotopes, nuclear imaging with positron emission tomography or gamma camera can be used to treat diseases and monitor therapy simultaneously. Such nuclear medicine technology is defined as radiation theragnosis. We review the current development of drugs and technology for radiation theragnosis using peptides, albumin, nanoparticles, and cells.

Oncogene-Driven Metabolic Alterations in Cancer

  • Min, Hye-Young;Lee, Ho-Young
    • Biomolecules & Therapeutics
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    • 제26권1호
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    • pp.45-56
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    • 2018
  • Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production. Moreover, oncogenic mutations are known to be associated with metabolic reprogramming in cancer, and these overall changes collectively influence tumor-microenvironment interactions and cancer progression. Accordingly, several agents targeting metabolic alterations in cancer have been extensively evaluated in preclinical and clinical settings. Additionally, metabolic reprogramming is considered a novel target to control cancers harboring un-targetable oncogenic alterations such as KRAS. Focusing on lung cancer, here, we highlight recent findings regarding metabolic rewiring in cancer, its association with oncogenic alterations, and therapeutic strategies to control deregulated metabolism in cancer.

Avian malaria associated with Plasmodium spp. infection in a penguin in Jeju Island

  • Ko, Kyeong-Nam;Kang, Sang-Chul;Jung, Ji-Youl;Bae, Jong-Hee;Kim, Jae-Hoon
    • 대한수의학회지
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    • 제48권2호
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    • pp.197-201
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    • 2008
  • Plasmodium spp. in domestic and wild birds are microscopic, intracellular parasitic protozoa within the blood cells and tissues cause avian malaria. A 17-month-old Magellan penguin (Spheniscus magellanicus) with a clinical signs of anorexia, depression, and respiratory distress for 3 days was submitted to the Pathology Department of Veterinary Medicine, Cheju National University in October 2005. It was born and reared in the Jeju Island. Grossly, the liver was enlarged, pale and friable. The spleen was also enlarged with dark red coloration and friable. Histopathologically, the lesions in the liver were characterized by multifocal infiltration of macrophages and lymphocytes especially in perivascular regions. The schizonts of Plasmodium spp. contained up to 30 merozoites were found in numerous infiltrated mononuclear cells. Similarly, histiocytic cells were proliferated in red pulp of spleen and the schizonts were found in these cells. Numerous dark brown pigments were widely distributed in the liver and spleen. The result of the nested polymerase chain reaction clarified the causative agent of this case was Plasmodium spp.. This is the first report for the outbreak of avian malaria caused by Plasmodium spp. in a penguin that was born and reared in Jeju Island in Korea.

Activation of JNK/p38 Pathway is Responsible for α-Methyl-n-butylshikonin Induced Mitochondria-Dependent Apoptosis in SW620 Human Colorectal Cancer Cells

  • Wang, Hai-Bing;Ma, Xiao-Qiong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권15호
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    • pp.6321-6326
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    • 2014
  • ${\alpha}$-Methyl-n-butylshikonin (MBS), one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells. MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of mitochondrial membrane potential. Additionally, MBS treatment led to activation of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced significant elevation in the phosphorylation of JNK and p38. Pretreatment of SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580) abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling pathway, and provided a clue for preclinical and clinical evaluation of MBS for colorectal cancer therapy.

A case of polypoid cystitis in a dog

  • Im, Eo-Jin;Kang, Sang-Chul;Jung, Ji-Youl;Jeon, Jae-Nam;Kim, Jae-Hoon
    • 대한수의학회지
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    • 제49권2호
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    • pp.163-166
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    • 2009
  • Among benign proliferation of the urinary bladder, polypoid cystitis is a rare disease in dogs. It is characterized by epithelial proliferation, chronic inflammation in lamina propria, and development of a polypoid mass or masses without evidence of neoplasia. This report describes histopathologic features of polypoid cystitis in dog. A 10-year-old spayed female shihtzu-dog was presented with two-month history of hematuria. Abdominal ultrasonography confirmed the thickened bladder wall and calculi in both kidneys. Surgical biopsy sample was taken from the thickened bladder mucosa for the histopathologic examination. The mass was covered with irregular hyperplastic transitional epithelium with the projection into the lumen in multifocal areas as well as many Brunn's nests in lamina propria. Many inflammatory cells such as lymphocyte, plasma cell, and macrophage and few neutrophils were occupied in lamina propria and submucosa. Proliferated fibrous tissues in lamina propria were clarified by using special staining methods. These collagens were stained blue with Masson's trichrome and red with van Gieson, but negative for alcian blue. Based on the clinical, gross, and histopathologic examinations, this case was diagnosed as polypoid cystitis in a dog. In our best knowledge, this is the first report of polypoid cystitis in dog in Korea.

Cutaneous smooth muscle tumors in 3 dogs

  • Jung, Ji-Youl;Kang, Sang-Chul;Park, Dae-Sik;Lee, Eun-Sung;Bae, Jong-Hee;Kim, Jae-Hoon
    • 대한수의학회지
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    • 제49권1호
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    • pp.63-66
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    • 2009
  • Cutaneous leiomyomas (leiomyosarcomas) are smooth muscle tumors that occur single or as multiple lesions. They usually arise from the arrector pili muscles (piloleiomyomas) and less commonly from the muscle of veins (angioleiomyomas). This report describes histologic and immunohistochemical features of one cutaneous piloleiomyoma and two angioleiomyosarcomas. Three 7-12-year-old female dogs were presented with single or double cutaneous nodules. Histologically, the neoplastic masses were composed of densely or loosely arranged interlacing bundles. The neoplastic cells were ovoid to elongate, and had eosinophilic cytoplasms and perinuclear cytoplasmic vacuolation. Nuclei were central to eccentric, cigar shaped, oval to elongate. In two cases, high mitotic index in high power field, multifocal necrosis and local invasion were also noted. Masson's trichrome and van Gieson staining revealed muscle origin tumors in these cases. Immunohistochemically, the tumor cells were strongly positive for smooth muscle actin. In our best knowledge, this is the first report of cutaneous smooth muscle tumors in dogs in Korea.

Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies

  • Yuan, Hai-Dan;Kim, Jung-Tae;Kim, Sung-Hoon;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • 제36권1호
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    • pp.27-39
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    • 2012
  • Panax ginseng exhibits pleiotropic beneficial effects on cardiovascular system, central nervous system, and immune system. In the last decade, numerous preclinical findings suggest ginseng as a promising therapeutic agent for diabetes prevention and treatment. The mechanism of ginseng and its active components is complex and is demonstrated to either modulate insulin production/secretion, glucose metabolism and uptake, or inflammatory pathway in both insulin-dependent and insulin-independent manners. However, human studies are remained obscure because of contradictory results. While more studies are warranted to further understand these contradictions, ginseng holds promise as a therapeutic agent for diabetes prevention and treatment. This review summarizes the evidences for the therapeutic potential of ginseng and ginsenosides from in vitro studies, animal studies and human clinical trials with a focus on diverse molecular targets including an AMP-activated protein kinase signaling pathway.

Suppressing breast cancer by exercise: consideration to animal models and exercise protocols

  • Lee, Jea Jun;Beak, Suji;Ahn, Sang Hyun;Moon, Byung Seok;Kim, Jisu;Lee, Kang Pa
    • 운동영양학회지
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    • 제24권2호
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    • pp.22-29
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    • 2020
  • [Purpose] Exercise is thought to have a significant effect on chemotherapy, and previous studies have reported that exercise can increase patient survival. Thus, in this review, we aimed to summarize various animal models to analyze the effects of exercise on breast cancer. [Methods] We summarized types of breast cancer animal models from various reports and analyzed the effects of exercise on anti-cancer factors in breast cancer animal models. [Results] This review aimed to systematically investigate if exercise could aid in suppressing breast cancer. Our study includes (a) increase in survival rate through exercise; (b) the intensity of exercise should be consistent and increased; (c) a mechanism for inhibiting carcinogenesis through exercise; (d) effects of exercise on anti-cancer function. [Conclusion] This review suggested the necessity of a variety of animal models for preclinical studies prior to breast cancer clinical trials. It also provides evidence to support the view that exercise plays an important role in the prevention or treatment of breast cancer by influencing anticancer factors.

Optical Coherence Tomography Applications for Dental Diagnostic Imaging: Prototype System Performance and Preclinical Trial

  • Eun Seo Choi;Won-Jin Yi;Chang-Seok Kim;Woosub Song;Byeong-il Lee
    • Current Optics and Photonics
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    • 제7권3호
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    • pp.283-296
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    • 2023
  • An intraoral spectral domain optical coherence tomography (SD-OCT) system has been developed, using a custom-built hand-held scanner and spectrometer. The hand-held OCT probe, based on a microelectromechanical systems scanner and a self-built miniaturized drive circuit, had a field of view sufficient for dental diagnosis. The spectrometer using a fabricated f-theta lens provided the image depth required for dental diagnosis. The axial and transverse resolutions of the OCT system in air were 7.5 ㎛ and 12 ㎛ respectively. The hand-held probe could scan an area of 10 × 10 mm2, and the spectrometer could image along a depth of 2.5 mm. To verify the utility of the developed OCT system, OCT images of tooth hard and soft tissues were acquired, and a user-interface program for diagnosis was developed. Early caries and microcracks that were difficult to diagnose with existing methods could be found, and the state of restoration could be observed. Measuring the depth of the gingival sulcus, distinguishing subgingival calculus, and detecting an implant under the gingiva suggested the possibility of the SD-OCT system as a diagnostic for dental soft tissues. Through the presented OCT images, the capability of the developed SD-OCT system for dental diagnosis was demonstrated.

Prediction of radiation dose to adult human from radiopharmaceutical manufactured by third generation bisphosphonate labeled with Rhenium

  • Zahra Pourhabib;Hassan Ranjbar
    • Nuclear Engineering and Technology
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    • 제55권2호
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    • pp.669-673
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    • 2023
  • Introduction: The crucial step in preclinical process of radiopharmaceutical production is internal dosimetry evaluation by different ways to realize radiobiological dose-response relationships and to extract the results for clinical use. Till now several bone-seeking radiopharmaceuticals have been developed for bone metastasis. Interesting features of bisphosphonates attracted attentions to them in the field of radiopharmaceutical therapy and studies on new generation of them have been doing too. Materials and methods: In this study, we used ZNA as representative of the third generation. The radiopharmaceutical 188Re-ZNA was produced and its radiochemical purity was investigated. Then, the biological distribution of the produced radiopharmaceutical at 1, 2, 4 and 24 h after injection on different organs of mice were investigated. Finally, the absorbed dose of organs in the human body was assessed using the RADAR method. Results: The results show 96% radiochemical purity of the 188Re-ZNA radiopharmaceutical. The amount of %ID/g in bone is 1.131% after 1 h and in 24 h it has a significant amount compared to other organs, that is 0.516%. Also dosimetric results show that the highest absorption dose is related to bone and the amount of this dose is 0.050 mGy/MBq. Conclusion: Considering the possibility of producing the 188Re-ZNA radiopharmaceutical, as well as the proper distribution of this radiopharmaceutical in target and non-target organs and increasing the absorbed dose in bone, it can be concluded that this radiopharmaceutical can be useful in the "radiopharmaceutical therapy" in metastases.