• Title/Summary/Keyword: Tissue-specific agents

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Biopsy and Mutation Detection Strategies in Non-Small Cell Lung Cancer

  • Jung, Chi Young
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.5
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    • pp.181-187
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    • 2013
  • The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.

Molecular Imaging of Stretch-Induced Tissue Factor Expression in Carotid Arteries with Intravascular Ultrasound

  • Park Byung-Rae
    • Biomedical Science Letters
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    • v.11 no.1
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    • pp.23-29
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    • 2005
  • Molecular imaging with targeted contrast agents enables tissues to be distinguished by detecting specific cell-surface receptors. In the present study, a ligand-targeted acoustic nanoparticle system is used to identify angioplasty-induced expression of tissue factor by smooth muscle cell within carotid arteries. Pig carotid arteries were overstretched with balloon catheters, treated with tissue factor-targeted or a control nanoparticle system, and imaged with intravascular ultrasound before and after treatment. Tissue factor-targeted emulsion bound and increased the echogenicity and gray-scale levels of overstretched smooth muscle cell within the tunica media, versus no change in contralateral control arteries. Expression of stretch-induced tissue factor in carotid artery media was confirmed by immunohistochemistry. The potential for abnormal thrombogenicity of balloon-injured arteries, as reflected by smooth muscle expression of tissue factor, was imaged using a novel, targeted, nanoparticulate ultrasonic contrast agent.

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Chemometric Studies on Brain-uptake of PET Agents via VolSurf Analysis

  • Lee, Hyo-Seon;Kim, Mi-Kyoung;Lee, Chae-Woon;Kim, Jin-Young;Choo, Il-Han;Woo, Jong-Inn;Chong, You-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.29 no.1
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    • pp.61-68
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    • 2008
  • High initial (2 minutes after iv injection) brain-uptake of PET agents is required to deliver the agent to binding sites in brain tissue but, for quantification of the specific binding, relatively rapid washout of free and non-specifically bound PET agents from the brain (30 minutes after injection) also is required. In order to compare the physicochemical properties of the PET agents which are responsible for early brain-uptake and rapid washout, respectively, chemometric analysis on brain-uptake of PET agents was performed via a classical VolSurf approach. According to the PCA and PLS results, high 2-30 min brain-uptake ratio seems to be related to the large hydrophobic regions in the PET agents which are not confined to a particular surface.

Navigating the Landscape of Intestinal Regeneration: A Spotlight on Quiescence Regulation and Fetal Reprogramming

  • Su-Jeong Oh;Yoojin Seo;Hyung-Sik Kim
    • International Journal of Stem Cells
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    • v.17 no.3
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    • pp.213-223
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    • 2024
  • Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with in vitro organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.

Effects of Fenofibrate on Adipogenesis in Female C57BL/6J Mice

  • Jeong Sunhyo;Choi Won Chang;Yoon Michung
    • Biomedical Science Letters
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    • v.11 no.1
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    • pp.1-8
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    • 2005
  • Fibrates are a class of hypolipidemic agents whose effects are mediated by activation of a specific transcription factor called the peroxisome proliferator-activated receptor $\alpha\;(PPAR\alpha).\;PPAR\alpha$ regulates the pathways of lipid catabolism such as fatty acid oxidation and the triglyceride metabolism, resulting in the treatment of hyperlipidemia. The decreased levels of plasma triglycerides by fibrates are responsible for hypertrophy and hyperpalsia of adipose cells. To determine whether fenofibrate regulates adipogenesis in female C57BL/6J mice, we measured the effects of fenofibrate on not only body weight, adipose tissue mass and serum triglycerides, but also the histology of adipose tissue and the expression of adipocyte marker genes. Fenofibrate did not inhibit high fat diet-induced increases in body weight, adipose tissue mass and serum triglycerides. Furthermore, fenofibrate did not cause the changes in the size and number of adipocytes and the expression of adipocyte-specific genes such as leptin and $TNF\alpha$. Therefore, this study demonstrates that fenofibrate does not affect adipogenesis in female mice.

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MR Study of Wate Exchange and Cell Membrane Permeability in Rat Liver Cells Using a Tissue-Specific MR Contrast Agent (조직 특성 MR 조영제를 이용한 쥐의 간세포막의 물분자 교환 및 투과율의 MR 측정기법)

  • Yongmin Chang
    • Investigative Magnetic Resonance Imaging
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    • v.2 no.1
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    • pp.73-82
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    • 1998
  • Purpose : A precise NMR technique for measuring the rate of water exchange and cell membrane permeability across the hepatocyte membrane using liver-specific MR contrast agent is described. Materials and Methods : The rat hepatocytes isolated by perfusion of the livers were used for the NMR measurements. All experiments were performed on an IBM field cycling relaxometer operating from 0.02MHz to 60 MHz proton Larmor frequency. spin-echo pulse sequence was empolyed to measure spin-lattice relaxation time, T1. The continuous distribution analysis of water proton T1 data from rat hepatocytes containing low concentrations of the liver specific contrast agent, Gd-EOB-DTPA, modeled by a general two compartment exchange model. Results : The mean residence time of water molecule inside the hepatocyte was approximately 250 msec. The lower limit for the permeability of the hepatocyte membrane was $(1.3{\pm}0.1){\;}{\times}{\;}10^{-3}cm/sec$. The CONTIN analysis, which seeks the natural distribution of relaxation times, reveals direct evidence of the effect of diffusive exchange. the diffusive water exchange is not small in the intracellular space in the case of hepatocytes. Conclusions : Gd-EOB-DTPA, when combined with continuous distribution analysis, provides a robust method to study water exchange and membrane permeability in hepatocytes. Water exchange in hepatocyte is much slower thatn that in red blood cells. Therefore, tissue-specific contrast agent may be used as a functional agent to give physiological information such as cell membrane permeability.

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Gene Expression Patterns of Spleen, Lung and Brain with Different Radiosensitivity in C57BL6 Mice

  • Majumder Md. Zahidur Rahman;Lee, Woo-Jung;Lee, Su-Jae;Bae, Sang-Woo;Lee, Yun-Sil
    • Journal of Radiation Protection and Research
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    • v.30 no.4
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    • pp.197-208
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    • 2005
  • Although little information is available on the underlying mechanisms, various genetic factors have been associated with tissue-specific responses to radiation. In the present study, we explored the possibility whether organ specific gene expression is associated with radiosensitivity using samples from brain, lung and spleen. We examined intrinsic expression pattern of 23 genes in the organs by semi-quantitative RT-PCR method using both male and female C57BL/6 mice. Expression of p53 and p21, well known factors for governing sensitivity to radiation or chemotherapeutic agents, was not different among the organ types. Both higher expression of sialyltransferase, delta7-sterol reductase, leptin receptor splice variant form 12.1, and Cu/Zn superoxide dismutase (SOD) and lower expression of alphaB crystalline were specific for spleen tissue. Expression level of glutathione peroxidase and APO-1 cell surface antigen gene in lung tissue was high, while that of Na, K-ATPase alpha-subunit, Cu/ZnSOD, and cyclin G was low. Brain, radioresistant organ, showed higher expressions of Na, K-ATPase-subunit, cyclin G, and nucleolar protein hNop56 and lower expression of delta7-sterol reductase. The result revealed a potential correlation between gene expression patterns and organ sensitivity, and Identified genes which might be responsible for organ sensitivity.

Clinical development of photodynamic agents and therapeutic applications

  • Baskaran, Rengarajan;Lee, Junghan;Yang, Su-Geun
    • Biomaterials Research
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    • v.22 no.4
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    • pp.303-310
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    • 2018
  • Background: Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic treatments have been extensively studied and the photosensitizers (PS) are key to their biological efficacy, while laser and oxygen allow to appropriate and flexible delivery for treatment of diseases. Introduction: In presence of oxygen and the specific light triggering, PS is activated from its ground state into an excited singlet state, generates reactive oxygen species (ROS) and induces apoptosis of cancer tissues. Those PS can be divided by its specific efficiency of ROS generation, absorption wavelength and chemical structure. Main body: Up to dates, several PS were approved for clinical applications or under clinical trials. $Photofrin^{(R)}$ is the first clinically approved photosensitizer for the treatment of cancer. The second generation of PS, Porfimer sodium ($Photofrin^{(R)}$), Temoporfin ($Foscan^{(R)}$), Motexafin lutetium, Palladium bacteriopheophorbide, $Purlytin^{(R)}$, Verteporfin ($Visudyne{(R)}$), Talaporfin ($Laserphyrin^{(R)}$) are clinically approved or under-clinical trials. Now, third generation of PS, which can dramatically improve cancer-targeting efficiency by chemical modification, nano-delivery system or antibody conjugation, are extensively studied for clinical development. Conclusion: Here, we discuss up-to-date information on FDA-approved photodynamic agents, the clinical benefits of these agents. However, PDT is still dearth for the treatment of diseases in specifically deep tissue cancer. Next generation PS will be addressed in the future for PDT. We also provide clinical unmet need for the design of new photosensitizers.

Diabetes, Glucose Transport and Hypoglycaemic Agents

  • Khil, Lee-Yong
    • Biomolecules & Therapeutics
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    • v.12 no.4
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    • pp.202-208
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    • 2004
  • Diabetes mellitus is a complex metabolic derangement with hyperglycaemia being the most characteristic symptom of diabetes. Hyperglycaemia can be caused by an increase in the rate of glucose production by the liver or by a decrease in the rate of glucose use by peripheral tissues. Impaired glucose transport is one of the major factors contributing to insulin resistance in type 2 diabetic patients. The ability of insulin to mediate tissue glucose uptake is a critical step in maintaining glucose homeostasis and in clearing the post-prandial glucose load. Glucose transport is mediated by specific carriers called glucose transporters (GLUTs). In this article, the functional importance and molecular mechanisms of insulin-induced glucose transport and development of hypoglycaemic agents which increase glucose transport are reviewed.