• Title/Summary/Keyword: Targeted agent

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An Efficient Agent Framework for Host-based Vulnerability Assessment System in Virtualization Environment (가상화 환경에서 호스트 기반 취약점 분석 시스템을 위한 효율적인 에이전트 프레임워크)

  • Yang, Jin-Seok;Chung, Tai-Myoung
    • KIPS Transactions on Computer and Communication Systems
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    • v.3 no.1
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    • pp.23-30
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    • 2014
  • In this paper, we propose an efficient agent framework for host-based vulnerability assessment system by analyzing the operational concept of traditional vulnerability assessment framework and proposed vulnerability assessment agent framework in virtualization environment. A proposed agent framework have concept by using the features of virtualization technology, it copy and execute checking agent in targeted virtual machines. In order to embody a propose agent framework, we design function block of checking agent and describe a vulnerability checking scenario of proposed agent framework. Also we develop pilot system for vulnerability checking scenario. We improve the shortcomings of the traditional vulnerability assessment system, such as unnecessary system load of the agent, inefficiency due to duplication agent installation. Moreover, the proposed agent framework is maximizing the scalability of the system because there is no agent installation when adding a targeted system.

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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A Case Report of Partial Remission of Renal Cell Carcinoma with Multiple Liver Metastases Treated with Korean Herbal Medicine in Conjunction with Targeted Anticancer Therapy Afinitor (한약치료와 표적항암요법(아피니토)을 병행하여 부분 관해 된 신세포암 간전이 환자 1례)

  • Chang, Sung-Hwan;Park, Ji-Hye;Yoo, Hwa Seung
    • Journal of Korean Traditional Oncology
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    • v.22 no.2
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    • pp.13-24
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    • 2017
  • Objectives: The purpose of this study is to report the effect of Korean Herbal Medicine (KHM) on a Renal Cell Carcinoma with multiple liver metastases patient. Methods: One renal cell carcinoma with multiple liver metastases patient was treated by KHM in conjunction with targeted anticancer agent (Afinitor). The effect of KHM was measured by scanning with Computed Tomography (CT), Blood Test, Visual Analogue Scale (VAS) and Eastern Cooperative Oncology Group scale. Results: Multiple hepatic tumors were reduced after the treatment during 5 months (Partial Remission, PR). As treatment was performed, complications induced by targeted anticancer agent (Afinitor) were alleviated. Conclusions: This case provides us a possibility that Korean Herbal Medicine offers potential benefits for renal cell carcinoma with multiple liver metastases patient.

Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

Novel artesunate-metformin conjugate inhibits bladder cancer cell growth associated with Clusterin/SREBP1/FASN signaling pathway

  • Peiyu Lin;Xiyue Yang;Linghui Wang;Xin Zou;Lingli Mu;Cangcang Xu;Xiaoping Yang
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.3
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    • pp.219-227
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    • 2024
  • Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

The Inhibition of Melanogenesis Via the PKA and ERK Signaling Pathways by Chlamydomonas reinhardtii Extract in B16F10 Melanoma Cells and Artificial Human Skin Equivalents

  • Lee, Ayeong;Kim, Ji Yea;Heo, Jina;Cho, Dae-Hyun;Kim, Hee-Sik;An, In-Sook;An, Sungkwan;Bae, Seunghee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.2121-2132
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    • 2018
  • Abnormal melanin synthesis results in several hyperpigmentary disorders such as freckles, melanoderma, age spots, and other related conditions. In this study, we investigated the anti-melanogenic effects of an extract from the microalgae Chlamydomonas reinhardtii (CE) and potential mechanisms responsible for its inhibitory effect in B16F10, normal human epidermal melanocyte cells, and human skin-equivalent models. The CE extract showed significant dose-dependent inhibitory effects on ${\alpha}$-melanocyte-stimulating, hormone-induced melanin synthesis in cells. Additionally, the CE extract exhibited suppressive effects on the mRNA and protein expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. The CE extract also inhibited the phosphorylation of protein kinase A and extracellular signal-related kinase, which function as upstream regulators of melanogenesis. Using a three-dimensional, reconstructed pigmented epidermis model, the CE-mediated, anti-pigmentation effects were confirmed by Fontana-Masson staining and melanin content assays. Taken together, CE extract can be used as an anti-pigmentation agent.

Preparation of Curcumin-loaded Dequalinium Emulsion for Mitochondria-targeted Drug Delivery (미토콘드리아 표적 약물 전달을 위한 curcumin 함유 dequalinium emulsion 제조)

  • Hye Won Park;Joon Sig Choi
    • Applied Chemistry for Engineering
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    • v.35 no.5
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    • pp.451-457
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    • 2024
  • This study focused on the development of a dequalinium-containing oil-in-water (O/W) emulsion (DQE) system for delivering the mitochondria-targeted anticancer agent, curcumin. Dequalinium is a mitochondria-targeting agent with known antibacterial and anticancer properties, and its efficacy in treating malaria has been previously recognized. Structurally, dequalinium is amphiphilic, comprising hydrophobic methylene and hydrophilic quinaldinium groups. In this study, curcumin, a well-documented anticancer and antioxidant compound, was incorporated into the oil phase of an emulsion using dequalinium as the emulsifier. Castor oil, chosen for its biodegradability and high stability in the body, was used as the oil phase in this study. The curcumin-loaded DQE was prepared using ultrasonic sonication followed by homogenization. The morphology and size distribution of the emulsion particles, as assessed using nanoparticle analysis, atomic force microscopy, and transmission electron microscopy, ranged from 100-200 nm. Confocal microscopy confirmed the efficient mitochondrial targeting ability of DQE in HeLa cells. These findings establish the DQE system as a promising drug delivery platform with efficient mitochondrial targeting capabilities and the potential to encapsulate water-insoluble drugs.

Monoterpenoid Loliolide Regulates Hair Follicle Inductivity of Human Dermal Papilla Cells by Activating the AKT/β-Catenin Signaling Pathway

  • Lee, Yu Rim;Bae, Seunghee;Kim, Ji Yea;Lee, Junwoo;Cho, Dae-Hyun;Kim, Hee-Sik;An, In-Sook;An, Sungkwan
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1830-1840
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    • 2019
  • Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a three-dimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of β-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/β-catenin signaling pathway.

Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

Detection of Vibrio vulnificus by Real-Time PCR targeted to rpoS gene (rpoS 유전자를 대상으로 하는 Real-Time PCR에 의한 Vibrio vulnificus 검출)

  • Kim, Dong-Gyun;Ahn, Sun-Hee;Bae, Ju-Yoon;Kong, In-Soo
    • Journal of Marine Bioscience and Biotechnology
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    • v.2 no.4
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    • pp.263-266
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    • 2007
  • Vibrio vulnificusis a causative agent of serious diseases in humans resulting from the contact of wound with seawater or consumption of raw seafood. Several studies aimed at detecting V. vulnificus have targeted vvh as a representative virulence toxin gene belonging to the bacterium. In this study, we targeted the rpoS gene, a general stress regulator, to detect V. vulnificus. PCR specificity was identified by amplification of 8 V. vulnificus templates and by the loss of a PCR product with 36 non-V. vulnificus strains. The PCR assay had the 273-bp fragment and the sensitivity of 10 pg DNA from V. vulnificus. SYBR Green I-based real-time PCR assay targeting the rpoS gene showed a melting temperature of approximately $84^{\circ}C$ for V. vulnificus strains. The minimum level of detection by real-time PCR was 2 pg of purified genomic DNA, or $10^3$ V. vulnificus cells from pure cultured broth and $10^3$ cells in 1g of oyster tissue homogenates. These data indicate that real-time PCR is a sensitive, species-specific, and rapid method for detecting this bacterium using the rpoS gene in pure cultures and in infected oyster tissues.

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