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Pharmacology & therapeutics 16건

  1. [해외논문]   Editorial Board   SCI SCIE


    Pharmacology & therapeutics v.181 ,pp. ii - ii , 2018 , 0163-7258 ,

    초록

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  2. [해외논문]   The challenges and promise of targeting the Liver X Receptors for treatment of inflammatory disease   SCI SCIE

    Fessler, Michael B.
    Pharmacology & therapeutics v.181 ,pp. 1 - 12 , 2018 , 0163-7258 ,

    초록

    Abstract The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models. Although this has suggested potential for application to human disease, systemic LXR activation is complicated by hepatic steatosis and hypertriglyceridemia, consequences of lipogenic gene induction in the liver by LXRα. The past several years have seen the development of multiple advanced LXR therapeutics aiming to avoid hepatic lipogenesis, including LXRβ-selective agonists, tissue-selective agonists, and transrepression-selective agonists. Although several synthetic LXR agonists have made it to phase I clinical trials, none have progressed due to unforeseen adverse reactions or undisclosed reasons. Nonetheless, several sophisticated pharmacologic strategies, including structure-guided drug design, cell-specific drug targeting, as well as non-systemic drug routes have been initiated and remain to be comprehensively explored. In addition, recent studies have identified potential utility for targeting the LXRs during therapy with other agents, such as glucocorticoids and rexinoids. Despite the pitfalls encountered to date in translation of LXR agonists to human disease, it appears likely that this accelerating field will ultimately yield effective and safe applications for LXR targeting in humans.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  3. [해외논문]   Significance of A-to-I RNA editing of transcripts modulating pharmacokinetics and pharmacodynamics   SCI SCIE

    Nakano, Masataka (Corresponding author at: Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.) , Nakajima, Miki
    Pharmacology & therapeutics v.181 ,pp. 13 - 21 , 2018 , 0163-7258 ,

    초록

    Abstract RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation. It became apparent that disrupted RNA editing or abnormal ADAR expression is associated with several diseases including cancer, neurological disorders, metabolic diseases, viral infections, and autoimmune disorders. The biological significance of RNA editing in pharmacokinetics/pharmacodynamics (PK/PD)-related genes is starting to be demonstrated. The authors conducted pioneering studies to reveal that RNA editing modulates drug metabolism potencies in the human liver, as well as the response of cancer cells to chemotherapy agents. Awareness of the importance of RNA editing in drug therapy is growing. This review summarizes the current knowledge on the RNA editing that affects the expression and function of drug response-related genes. Continuing studies on the RNA editing that regulates pharmacokinetics/pharmacodynamics would provide new beneficial information for personalized medicine.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  4. [해외논문]   Stable isotope-based flux studies in nonalcoholic fatty liver disease   SCI SCIE

    McCullough, Arthur (Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, OH, USA ) , Previs, Stephen (Merck & Co., Inc., Kenilworth, NJ, USA ) , Kasumov, Takhar (Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, OH, USA)
    Pharmacology & therapeutics v.181 ,pp. 22 - 33 , 2018 , 0163-7258 ,

    초록

    Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression. This review focuses mainly on the utilization of mass spectrometry-based methods for the understanding of metabolic abnormalities in the different stages of NAFLD. For example, stable isotope-based flux studies demonstrated multi-organ insulin resistance, dysregulated glucose, lipids and lipoprotein metabolism in patients with NAFLD. We also review recent developments in the stable isotope-based technologies for the study of mitochondrial dysfunction, oxidative stress and fibrogenesis in NAFLD. We highlight the limitations of current methodologies, discuss the emerging areas of research in this field, and future directions for the applications of stable isotopes to study NAFLD and its complications.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  5. [해외논문]   Multifunctional molecule ERp57: From cancer to neurodegenerative diseases   SCI SCIE

    Hettinghouse, Aubryanna (Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA ) , Liu, Ronghan (Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA ) , Liu, Chuan-ju (Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA)
    Pharmacology & therapeutics v.181 ,pp. 34 - 48 , 2018 , 0163-7258 ,

    초록

    Abstract The protein disulfide isomerase (PDI) gene family is a protein family classically characterized by endoplasmic reticulum (ER) localization and isomerase and redox activity. ERp57, a prominent multifunctional member of the PDI family, is detected at various levels in multiple cellular localizations outside of the ER. ERp57 has been functionally linked to a host of physiological processes and numerous studies have demonstrated altered expression and aberrant functionality of ERp57 in association with diverse pathological states. Here, we summarize available knowledge of ERp57's functions in subcellular compartments and the roles of dysregulated ERp57 in various diseases toward an emphasis on the potential utility of therapeutic development of ERp57.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  6. [해외논문]   Unravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours   SCI SCIE

    Neuzillet, Cindy (INSERM UMR1149, Beaujon University Hospital (Assistance Publique-Hôpitaux de Paris, AP-HP), Paris 7 Diderot University, 100 Boulevard du Général Leclerc, 92110 Clichy, France ) , de Mestier, Louis (INSERM UMR1149, Beaujon University Hospital (Assistance Publique-Hôpitaux de Paris, AP-HP), Paris 7 Diderot University, 100 Boulevard du Général Leclerc, 92110 Clichy, France ) , Rousseau, Benoî (Department of Medical Oncology, Henri Mondor University Hospital (AP-HP), Paris Est Créteil University (UPEC), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France ) , t (Department of Cancer Medicine - Sarcoma Group, Department of Early Drug Development (DITEP) - Phase 1 Unit, Gustave Roussy Cancer Campus, University of Paris Sud, 114, Rue Edouard Vaillant, 94800 Villejuif, France ) , Mir, Olivier (Department of Medical Oncology, Lille University Hospital, 1, Rue Polonovski, 59037 Lille, France ) , Hebbar, Mohamed (Tumour Biology Laboratory, Barts Cancer Institute, Queen Mary University of London, Chart) , Kocher, Hemant M. , Ruszniewski, Philippe , Tournigand, Christophe
    Pharmacology & therapeutics v.181 ,pp. 49 - 75 , 2018 , 0163-7258 ,

    초록

    Abstract Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies. Targeted agents have provided clinical benefit in many GI cancer types. Particularly, some GI tumours are considered chemoresistant and targeted therapies have offered a new therapeutic base for their management. Hence, somatostatin receptor-directed strategies, sorafenib, and imatinib have revolutioned the management of neuroendocrine tumours (NET), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumours (GIST), respectively, and are now used as first-line treatment in many patients affected by these tumours. However, these agents face problems of resistances and identification of predictive biomarkers from imaging and/or biology. We propose a comprehensive two-part review providing a panoramic approach of the successes and failures of targeted agents in GI cancers to unravel the pharmacologic opportunities and future directions for these agents in GI oncology. In this second part, we will focus on NET, HCC, and GIST, whose treatment relies primarily on targeted therapies.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  7. [해외논문]   Oncogenic pathways that affect antitumor immune response and immune checkpoint blockade therapy   SCI SCIE

    Zhao, Xianda (Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, United States ) , Subramanian, Subbaya (Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, United States)
    Pharmacology & therapeutics v.181 ,pp. 76 - 84 , 2018 , 0163-7258 ,

    초록

    Abstract Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes—allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing. In preclinical tumor models, effective targeting of oncogenic pathways has enhanced the response to ICBT. Ongoing clinical trials are now evaluating combination therapy (i.e., the use of oncogenic pathway inhibitors in combination with ICBT). However, more translational and clinical research is needed, to optimize ICBT doses and sequence, minimize toxicity, and assess the impact on study participants of certain genetic backgrounds. Also, it is crucial to understand whether wild-type tumors with elevated oncogenic signaling will respond to combination therapy. Insights gained through current and future translational studies will provide the scientific premise and rationale to target 1 or more oncogenic pathways in ICBT-resistant tumors, thus enabling more human patients to benefit from combination therapy.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  8. [해외논문]   Polymyxins for CNS infections: Pharmacology and neurotoxicity   SCI SCIE

    Velkov, Tony (Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia ) , Dai, Chongshan (College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road, Beijing 100193, PR China ) , Ciccotosto, Giuseppe D. (Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia ) , Cappai, Roberto (Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia ) , Hoyer, Daniel (Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia ) , Li, Jian (Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia)
    Pharmacology & therapeutics v.181 ,pp. 85 - 90 , 2018 , 0163-7258 ,

    초록

    Abstract Central nervous system (CNS) infections caused by multi-drug resistant (MDR) Gram-negative bacteria present a major health and economic burden worldwide. Due to the nearly empty antibiotic discovery pipeline, polymyxins (i.e. polymyxin B and colistin) are used as the last-line therapy against Gram-negative ‘superbugs’ when all other treatment modalities have failed. The treatment of CNS infections due to multi-drug resistant Gram-negative bacteria is problematic and associated with high mortality rates. Colistin shows significant efficacy for the treatment of CNS infections caused by MDR Gram-negative bacteria that are resistant to all other antibiotics. In particular, MDR Acinetobacter baumannii , Pseudomonas aeruginosa and Klebsiella pneumoniae which are resistant to expanded-spectrum and fourth-generation cephalosporins, carbapenems and aminoglycosides, represent a major therapeutic challenge, although they can be treated with colistin or polymyxin B. However, current dosing recommendations of intrathecal/intraventricular polymyxins are largely empirical, as we have little understanding of the pharmacokinetics/pharmacodynamics and, importantly, we are only starting to understand the mechanisms of potential neurotoxicity. This review covers the current knowledge-base on the mechanisms of disposition and potential neurotoxicity of polymyxins as well as the combined use of neuroprotective agents to alleviate polymyxins-related neurotoxicity. Progress in this field will provide the urgently needed pharmacological information for safer and more efficacious intrathecal/intraventricular polymyxin therapy against life-threatening CNS infections caused by Gram-negative ‘superbugs’.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  9. [해외논문]   Toxicity profiles of immunotherapy   SCI SCIE

    Cousin, S. (Early Phase Trials Unit, Institut Bergonié, 229 Cours de l'Argonne, 33000 Bordeaux, France ) , Seneschal, J. (INSERM U1035, ATIP-AVENIR, Université) , Italiano, A. (de Bordeaux, Bordeaux, France )
    Pharmacology & therapeutics v.181 ,pp. 91 - 100 , 2018 , 0163-7258 ,

    초록

    Abstract Immunotherapies are changing the landscape of advanced solid tumor treatment. These therapies have different mechanisms of action and include oncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1 monoclonal antibodies, and CSF-1R antibodies. Given the growing therapeutic impact of these agents in oncology, it is important to better understand their properties. Immunotherapies generate new toxicity profiles that are called immune-related adverse events and require specific management. This review focuses on the mechanisms of action of such side effects, as well as their description and their general management.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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  10. [해외논문]   Emerging understanding of the mechanism of action of Bronchial Thermoplasty in asthma   SCI SCIE

    d'Hooghe, J.N.S. (Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ) , ten Hacken, N.H.T. (Department of Respiratory Medicine, University Medical Center Groningen, Groningen, The Netherlands ) , Weersink, E.J.M. (Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ) , Sterk, P.J. (Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ) , Annema, J.T. (Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ) , Bonta, P.I. (Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands)
    Pharmacology & therapeutics v.181 ,pp. 101 - 107 , 2018 , 0163-7258 ,

    초록

    Abstract Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate-to-severe asthma patients who are uncontrolled despite optimal medical therapy. Effectiveness of BT has been demonstrated in several randomized clinical trials. However, the asthma phenotype that benefits most of this treatment is unclear, partly because the mechanism of action is incompletely understood. BT was designed to reduce the amount of airway smooth muscle (ASM), but additional direct and indirect effects on airway pathophysiology are expected. This review will provide an overview of the different components of airway pathophysiology including remodeling, with the ASM as the key player. Current concepts in the understanding of BT clinical effectiveness with a focus on its impact on airway remodeling will be reviewed.

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    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

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