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- Volume 18, Issue 27, 2012
Current Pharmaceutical Design - Volume 18, Issue 27, 2012
Volume 18, Issue 27, 2012
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Context-dependent Action of Transforming Growth Factor β Family Members on Normal and Cancer Stem Cells
Authors: Laia Caja, Kaoru Kahata and Aristidis MoustakasThe transforming growth factor β (TGFβ) family embraces many growth factors including the Activins and bone morphogenetic proteins (BMPs). The pathways mediated by these growth factors are implicated in many fundamental biological processes such as early embryonic development, organ morphogenesis and adult tissue homeostasis and in a large number of pathologies including cancer. The action of these pathways Read More
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Deregulated Bone Morphogenetic Protein Receptor Signaling Underlies Fibrodysplasia Ossificans Progressiva
Authors: David J.J. de Gorter, Vishant Jankipersadsing and Peter ten DijkeTransforming growth factor-β family members, which include TGF-βs, activins and bone morphogenetic proteins (BMPs), play important roles in development and maintaining tissue homeostasis. The extracellular TGF-β family members signal across the plasmamembrane by activating type I and type II serine/threonine kinase receptors. Pertubation in TGF-β family receptor signaling has been implicated in certain diseases, incl Read More
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Cellular Players in Lung Fibrosis
Authors: Annemarie N. Lekkerkerker, Jamil Aarbiou, Thomas van Es and Richard A.J. JanssenPathogenic mechanisms involved in fibrosis of various organs share many common features. Myofibroblasts are thought to play a major role in fibrosis through excessive deposition of extracellular matrix during wound healing processes. Myofibroblasts are observed in fibrotic lesions, and whereas these derive from the hepatic stellate cells in liver, in lung they appear to originate from fibroblasts. The source of these fibrobl Read More
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TGFβ Signaling in Liver Regeneration
Authors: Sofia Karkampouna, Peter ten Dijke, Steven Dooley and Marianna Kruithof-de JulioAdult organ regeneration occurs in many systems such as in liver, skin, intestine and heart, indicating that postnatal life is not a static or quiescent state but a dynamic and complex process. The liver is a spectacular organ, exhibiting high regenerative capacity crucial for homeostasis and tissue repair: injuries induced mechanically or chemically, can be completely restored. Regeneration involves extensive cell division, inflammat Read More
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BMPS and Liver: More Questions than Answers
Authors: Blanca Herrera, Aranzazu Sanchez and Isabel FabregatBone morphogenetic proteins (BMPs) belong to the TGF-β superfamily and were first discovered as potent bone homeostasis regulators for their ability to induce endochondral bone formation, ectopic bone formation and fracture repair. A preeminent role of BMP signaling in developmental control of cell type specification, differentiation and organogenesis is also well established. More recently, a role for BMPs in adult tissue Read More
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TGF-Beta: a Master Switch in Tumor Immunity
Authors: Margherita Gigante, Loreto Gesualdo and Elena RanieriThe capacity of the immune system to distinguish foreign from self-antigen, and to subsequently eliminate the threat of disease without injuring the host is crucial for survival. It also serves to defend against tumor formation and progression via a process termed cancer immunosurveillance. Innate and adaptive immune cell types and effector molecules collectively function as extrinsic tumorsuppressor mechanisms. However, Read More
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TGF-β in Epithelial to Mesenchymal Transition and Metastasis of Liver Carcinoma
Authors: Patrick Reichl, Christine Haider, Markus Grubinger and Wolfgang MikulitsHepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) represent the majority of hepatic malignancies and are among the most frequent causes of cancer deaths worldwide with a rising incidence in western countries. Upon progression of liver cancer, the epithelial to mesenchymal transition (EMT) is considered a key process that drives intrahepatic metastasis. EMT is the transformation of epithelial cel Read More
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The TGF-β Signaling Pathway as a Pharmacological Target in a Hepatocellular Carcinoma
Authors: Antonio Mazzocca, Salvatore Antonaci and Gianluigi GiannelliHepatocellular carcinoma (HCC) is a cancer that usually develops on a liver already compromised by cirrhosis. Study of the underlying molecular mechanisms is essential so as to improve therapeutic strategies and to develop new pharmacological agents that may prevent or improve the course of this malignancy. Transforming growth factor-beta (TGF-β) intervenes in the process of hepatic fibrogenesis and cirrhosis, two p Read More
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TGF-Beta Inihibitor-loaded Polyelectrolyte Multilayers Capsules for Sustained Targeting of Hepatocarcinoma Cells
In this review we will report on recent advanced in polyelectrolyte capsules for targeted drug delivery (eg of growth factor inhibitor) against epatocarcinoma. Degradable polyelectrolyte multilayers capsules (PMCs) are of particular interest for cancer therapy since under physiological conditions they can be enzymatically degraded upon cell interaction. Small bioactive molecules such as TGFBeta inhibitors can be incorp Read More
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The Development of HEPT-Type HIV Non-Nucleoside Reverse Transcriptase Inhibitors and Its Implications for DABO Family
Authors: Wenmin Chen, Peng Zhan, Jingde Wu, Zhenyu Li and Xinyong Liu1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) was discovered as the first HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) in 1989. The research on HEPT derivatives (HEPTs) has been lasted for more than 20 years and HEPT family is probably the most investigated NNRTI. Extensive molecular modifications on HEPT have led to many highly potent compounds with broad-resistance spectr Read More
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Removal of the Tag from His-tagged ILYd4, a Human CD59 Inhibitor, Significantly Improves its Physical Properties and its Activity
Authors: Lin Wu, Sanbao Su, Fengming Liu, Tao Xu, Xiaoxiao Wang, Yan Huang, Xinlu Sun, Xiaowen Ge, Ting Chen, Huixia Liu, Chun Wang, Michael Chorev, Ting Xu and Xuebin QinComplement dependent cytotoxicity (CDC) significantly contributes to Rituximab (RTX) and Ofatumumab (OFA) efficacies in the treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Human CD59 (hCD59) is a key complement regulatory protein that restricts the formation of the membrane attack complex and thereby inhibits CDC. hCD59 is an important determinant of the sensitivity Read More
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Structure and Ligand-based Design of P-glycoprotein Inhibitors: A Historical Perspective
Computer-assisted drug design (CADD) is a valuable approach for the discovery of new chemical entities in the field of cancer therapy. There is a pressing need to design and develop new, selective, and safe drugs for the treatment of multidrug resistance (MDR) cancer forms, specifically active against P-glycoprotein (P-gp). Recently, a crystallographic structure for mouse P-gp was obtained. However, for decades the desi Read More
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Preclinical Safety and Pharmacokinetic Profile of 3K3A-APC, a Novel, Modified Activated Protein C for Ischemic Stroke
Activated protein C (APC), a protease with anticoagulant and cytoprotective activities, protects neurons and cerebrovascular endothelium from ischemic injury. A recombinant APC, drotrecogin alfa (activated) (DrotAA) (Xigris®), was approved by the Food and Drug Administration for the treatment of sepsis; however, serious bleeding was a dose-limiting side effect. A modified APC, containing 405 amino acid residues, 3K3 Read More
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New Therapeutic Strategies for Cancer and Neurodegeneration Emerging from Yeast Cell-based Systems
Authors: Clara Pereira, Mariana Leao, Joana Soares, Claudia Bessa and Lucilia SaraivaDespite great advances in understanding the molecular etiology of cancer and neurodegeneration, therapeutic strategies against these diseases are still largely lacking. Hence, acceleration of the discovery of new therapeutic agents against these pathologies is of enormous interest. This review is focused on the role of multi-faceted and expanding yeast cell-based systems in the search for new drugs and therapeutic targ Read More
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A Computational Study of the Oligosaccharide Binding Sites in the Lectin-Like Domain of Tumor Necrosis Factor and the TNF-derived TIP Peptide
Authors: Alexander Dulebo, Rudiger Ettrich, Rudolf Lucas and David KaftanThe lectin-like domain of Tumor Necrosis Factor (TNF), mimicked by the TIP peptide, activates amiloride-sensitive sodium uptake in type II alveolar epithelial cells and as such increases alveolar liquid clearance in dysfunctional lungs. This protective effect is blunted upon mutation of residues T105, E107 and E110 in human TNF into alanine or upon pre-incubation of the cytokine with the disaccharide N,N’-diacetylchitobiose. In Read More
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Target-based Anti-angiogenic Therapy in Breast Cancer
Authors: Markus Wehland, Johann Bauer, Manfred Infanger and Daniela GrimmBreast cancer is the most common female cancer. Despite advances in prevention, early diagnosis, and surgical treatment, its prognosis is still poor. Therefore, immunological and pharmacological methods of treatment have been emphasized recently. Prominent targets of drugs or antibodies are proteins, which are predominantly expressed on breast cancer cells and are simultaneously involved in promoting cell gr Read More
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The Effect of First-in-Class Small Molecule RhoA Inhibitor, HL07, on the Phenylephrine-induced Artery Contraction
Authors: Yan Zhang, Jing Deng, Sheng Ma, Lin Xue, Jin Zhu, Wei-liang Zhu, Hua-liang Jiang, Jian Li and Li-yan MiaoThe RhoA/ROCK inhibitors have emerged as a new promising treatment for cardiovascular diseases. Recently, we first reported a series of first-in-class small molecular RhoA inhibitors and a chemical compound named HL07 showed high RhoA inhibition activities. In this study, we aimed to explore the pharmacological effect and possible mechanism of HL07 on agonists-induced vasoconstriction. Results showed that 1) in rat Read More
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Volumes & issues
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Volume 31 (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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