Current drug targets. Immune, endocrine and metabolic disorders最新文献_第7页

Dendritic cell-based immunotherapy in thyroid malignancies. 基于树突状细胞的甲状腺恶性肿瘤免疫治疗。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-09-01 DOI: 10.2174/1568008043339820

Matthias Schott, Werner A Scherbaum, Jochen Seissler

引用次数: 6

Targeting the ERK pathway: novel therapeutics for thyroid cancer. 靶向ERK通路:甲状腺癌的新疗法。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-09-01 DOI: 10.2174/1568008043339785

Sandra F Williams, Robert C Smallridge

{"title":"Targeting the ERK pathway: novel therapeutics for thyroid cancer.","authors":"Sandra F Williams, Robert C Smallridge","doi":"10.2174/1568008043339785","DOIUrl":"https://doi.org/10.2174/1568008043339785","url":null,"abstract":"Over the past two decades significant progress has been made in elucidating the pathogenesis of thyroid cancer. The ongoing identification of mutations in cellular signaling pathways has revolutionized the field of thyroid cancer biology and has led to the development of novel new therapeutic agents. One of the signaling cascades implicated in the oncogenic process is the ERK pathway that normally functions to transmit mitogenic signals from the cell membrane to the nucleus. Genetic alterations of key components of this cascade, namely RET, Ras and Raf, are thought to result in constitutive activation of the pathway and subsequent thyroid tumorigenesis. Targeting of these components with pharmaceutical agents holds the potential of providing newer and more effective treatment modalities for thyroid cancer. Several such drugs are currently being developed to inhibit RET, Ras, Raf, as well as other factors impacted by the ERK pathway. These include a vast array of agents such as antisense compounds, small molecule inhibitors as well as inhibitors of farnesyl transferase, heat shock proteins, matrix metalloproteinases and histone deacetylases. Some of these drugs have already entered preclinical and clinical testing with promising anti-tumor effects. These as well as even newer agents may offer exciting possibilities for the future treatment of thyroid cancer.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 3","pages":"199-220"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24691561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

The PAX8/PPAR gamma fusion oncogene as a potential therapeutic target in follicular thyroid carcinoma. PAX8/PPAR融合癌基因作为滤泡性甲状腺癌的潜在治疗靶点。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-09-01 DOI: 10.2174/1568008043339802

Bryan McIver, Stefan K G Grebe, Norman L Eberhardt

{"title":"The PAX8/PPAR gamma fusion oncogene as a potential therapeutic target in follicular thyroid carcinoma.","authors":"Bryan McIver, Stefan K G Grebe, Norman L Eberhardt","doi":"10.2174/1568008043339802","DOIUrl":"https://doi.org/10.2174/1568008043339802","url":null,"abstract":"Follicular thyroid carcinoma (FTC) accounts for approximately 20% of all thyroid cancers, and up to 40% of the deaths associated with this disease. Current treatment approaches include surgery, followed by radioactive iodine therapy. However, a significant proportion of locally advanced and metastatic FTC fails to concentrate iodine. Because traditional chemotherapeutic agents have not been shown to alter outcomes in this disease, novel therapeutic strategies are needed for advanced disease. Recently, a genomic rearrangement has been identified in up to 50% of FTC, involving a translocation event between chromosome regions 3p25 and 2q13. This translocation fuses the thyroid-specific transcription factor PAX8 gene with the PPARgamma gene, a ubiquitously expressed transcription factor. We have confirmed that this Pax8/PPARgamma fusion gene (designated PPFP) is an oncogene, which accelerates cell growth, reduces rates of apoptosis and permits anchorage independent and contact uninhibited growth of a thyroid cell line. The action of PPFP arises, at least in part, through its activity as a dominant-negative inhibitor of the wild-type PPARgamma transcription factor. Although the mechanism by which PPFP impairs PPARgamma activity remains unknown at this time, it is likely to be mediated by competition for the genomic PPARgamma response elements, the endogenous ligand, or various cofactors, including the Retinoid X Receptor (RXR). Consequently, modulation of PPFP activity might be possible through the use of PPARgamma agonists, RXR-agonists, or specific modulators of PPFP itself. Alternatively, modulation of several down-stream regulatory pathways may become possible, as the consequences of PPARgamma inhibition become better known. PPFP represents a potential novel target for the management of advanced FTC.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 3","pages":"221-34"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008043339802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24691562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46

The sodium-iodide symporter. 碘化钠同调者。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-09-01 DOI: 10.2174/1568008043339839

C H Baker, J C Morris

引用次数: 35

Molecular elements of apoptosis-regulating pathways in follicular thyroid cells: mining for novel therapeutic targets in the treatment of thyroid carcinoma. 滤泡性甲状腺细胞凋亡调控通路的分子因子:甲状腺癌治疗的新靶点

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-09-01 DOI: 10.2174/1568008043339866

N J Sarlis, L Gourgiotis

{"title":"Molecular elements of apoptosis-regulating pathways in follicular thyroid cells: mining for novel therapeutic targets in the treatment of thyroid carcinoma.","authors":"N J Sarlis, L Gourgiotis","doi":"10.2174/1568008043339866","DOIUrl":"https://doi.org/10.2174/1568008043339866","url":null,"abstract":"Apoptosis or programmed cell death occurs in both normal and pathological conditions, including cancer. Dysregulation of apoptosis allows transformed cells to continually and uninhibitedly enter the cell cycle, thus perpetuating the sequence of mutation, genomic instability and, finally, oncogenesis. The cell death machinery includes cell surface receptors, adaptor molecules, proteolytic enzymes, such as caspases, and a variety of mitochondrial proteins, which interact with each other in a complex fashion. In addition, extensive \"cross-talk\" exists between the apoptotic pathways and several other signaling systems that govern growth and differentiation. Recent advances in molecular techniques have shed light upon elements of the above pathways in assorted malignancies, including non-medullary thyroid carcinoma (ThyrCa). A subgroup of ThyrCa patients is (or becomes over time) refractory to standard treatment modalities and eventually succumbs to their disease. For such patients with clinically aggressive ThyrCa, novel therapeutic agents are urgently needed. Changes in the sensitivity of cells to apoptosis have clear implications for the treatment of any malignancy. In this review, we outline the main molecular targets that play a role in apoptosis in ThyrCa cells, and discuss various options for promoting apoptosis, either by pharmacologic or gene transfer therapeutic interventions.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 3","pages":"187-98"},"PeriodicalIF":0.0,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24691560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Telomerase as drug and drug target for the treatment of thyroid cancer. 端粒酶作为治疗甲状腺癌的药物和药物靶点。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-09-01 DOI: 10.2174/1568008043339794

M A Zeiger, A K Meeker

引用次数: 2

Preface [Hot Topic: Endocrinology Meets Molecular Oncology: Beyond Radioactive Iodine (Guest Editor: Robert C. Smallridge)] 前言[热门话题:内分泌学与分子肿瘤学:超越放射性碘(特邀编辑:Robert C. Smallridge)]

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-08-31 DOI: 10.2174/1568008043339848

R. Smallridge

引用次数: 0

The pathobiology of osteoarthritis and the rationale for using the chondroitin sulfate for its treatment. 骨关节炎的病理生物学和使用硫酸软骨素治疗的基本原理。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-06-01 DOI: 10.2174/1568008043339929

Nicola Volpi

引用次数: 35

Flt3 ligand bioactivity and pharmacology in neoplasia. Flt3配体在肿瘤中的生物活性和药理学研究。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-06-01 DOI: 10.2174/1568008043339956

A J Reber, A E Ashour, S N Robinson, J E Talmadge, J C Solheim

{"title":"Flt3 ligand bioactivity and pharmacology in neoplasia.","authors":"A J Reber, A E Ashour, S N Robinson, J E Talmadge, J C Solheim","doi":"10.2174/1568008043339956","DOIUrl":"https://doi.org/10.2174/1568008043339956","url":null,"abstract":"Fms-like tyrosine kinase 3 ligand (Flt3L) has multiple effects on the hematopoietic and immune systems. Further, preclinical studies have suggested potential therapeutic activity against cancer. Flt3L is a potent hematopoietic cytokine, capable of stimulating the expansion and differentiation of hematopoietic progenitor and stem cells. Administration of Flt3L mobilizes hematopoietic cells from the bone marrow (BM) into the blood, lymphoid organs, and parenchymal tissues. This mobilization activity, especially effective in combination with granulocyte colony stimulating factor (G-CSF), has stimulated studies of Flt3L in hematopoietic stem cell (HSC) transplantation. In addition to its effects on hematopoietic stem and progenitor cells, Flt3L has been shown to increase the frequency and number of dendritic cells (DCs) within the circulatory system and solid organs. DC expansion by Flt3L has been the focus of preclinical and clinical studies on antigen (Ag) specific T-cell mediated immunity. The mechanism for the augmentation of T-cell mediated immunity has yet to be completely identified, although Flt3L's ability to expand DCs in lymphoid and non-lymphoid tissues is involved. This expansion occurs primarily with DCs, which secrete interleukin (IL) 12. Consistent with the expansion of this DC population, treatment with Flt3L enhances T-cell mitogenesis and preferentially induces type 1 T-cell responses. However, the DCs resulting from Flt3L administration are immature, leading in some studies to the induction of tolerance. This review focuses on the effects of Flt3L on DCs and other effector populations, and on its potential activity as a therapeutic agent for cancer, alone and in combination with vaccines.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 2","pages":"149-56"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008043339956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24551357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Regulators of G protein signaling: potential drug targets for controlling cardiovascular and immune function. G蛋白信号的调节因子:控制心血管和免疫功能的潜在药物靶点。

Current drug targets. Immune, endocrine and metabolic disorders Pub Date : 2004-06-01 DOI: 10.2174/1568008043339938

H Cho, K Harrison, J H Kehrl

{"title":"Regulators of G protein signaling: potential drug targets for controlling cardiovascular and immune function.","authors":"H Cho, K Harrison, J H Kehrl","doi":"10.2174/1568008043339938","DOIUrl":"https://doi.org/10.2174/1568008043339938","url":null,"abstract":"Heterotrimeric G-protein-coupled receptors (GPCRs) mediate a wide variety of organismal functions ranging from vision, olfaction, and gustation to the development and physiology of the cardiovascular, neuronal, and immune system. Naturally they are targets of a large number of therapeutic drugs. The regulators of G protein signaling (RGS) are a family of diverse proteins that regulate the GPCR-mediated signaling pathways principally by acting as GTPase activating proteins (GAPs) for the alpha subunit of the heterotrimeric G-proteins. Certain members of the RGS family contain multiple domains and motifs that mediate interactions with other signaling molecules, thus linking GPCR-dependent and GPCR-independent signaling pathways. Because of their ability to fine-tune vital GPCR-mediated processes and recent findings linking them to brain disorders, retinitis pigmentosa, and cancer RGS proteins have become excellent candidates for new drug discovery. The focus of this review is to discuss the roles of the RGS proteins in the development and normal physiology of cardiovascular and immune system, and to explore their potential as drug targets useful for the treatment of pathological conditions of the cardiovascular and immune systems.","PeriodicalId":84524,"journal":{"name":"Current drug targets. Immune, endocrine and metabolic disorders","volume":"4 2","pages":"107-18"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568008043339938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24551353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28