Drug Target Insights最新文献_第10页

Predictors of Virologic Failure in HIV/AIDS Patients Treated with Highly Active Antiretroviral Therapy in Brasília, Brazil During 2002-2008. 2002-2008年在巴西Brasília接受高活性抗逆转录病毒治疗的艾滋病毒/艾滋病患者病毒学失败的预测因素

IF 2.7

Drug Target Insights Pub Date : 2011-01-01 Epub Date: 2011-11-24 DOI: 10.4137/DTI.S7527

Edson José Monteiro Bello, Amabel Fernandes Correia, José Ricardo Pio Marins, Edgar Merchan-Hamann, Luis Isamu Barros Kanzaki

{"title":"Predictors of Virologic Failure in HIV/AIDS Patients Treated with Highly Active Antiretroviral Therapy in Brasília, Brazil During 2002-2008.","authors":"Edson José Monteiro Bello, Amabel Fernandes Correia, José Ricardo Pio Marins, Edgar Merchan-Hamann, Luis Isamu Barros Kanzaki","doi":"10.4137/DTI.S7527","DOIUrl":"https://doi.org/10.4137/DTI.S7527","url":null,"abstract":"Little data exists concerning the efficacy of the antiretroviral therapy in the Federal District in Brazil, therefore in order to improve HIV/AIDS patients' therapy and to pinpoint hot spots in the treatment, this research work was conducted. Of 139 HIV/AIDS patients submitted to the highly active antiretroviral therapy, 12.2% failed virologically. The significant associated factors related to unresponsiveness to the lentiviral treatment were: patients' place of origin (OR = 3.28; IC95% = 1.0-9.73; P = 0.032) and Mycobacterium tuberculosis infection (RR = 2.90; IC95% = 1.19-7.02; P = 0.019). In the logistic regression analysis, the remaining variables in the model were: patients' birthplace (OR = 3.28; IC95% = 1.10-9.73; P = 0.032) and tuberculosis comorbidity (OR = 3.82; IC95% = 1.19-12.22; P = 0.024). The patients enrolled in this survey had an 88.0% therapeutic success rate for the maximum period of one year of treatment, predicting that T CD4(+) low values and elevated viral loads at pretreatment should be particularly considered in tuberculosis coinfection, besides the availability of new antiretroviral drugs displaying optimal activity both in viral suppression and immunological reconstitution.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"5 ","pages":"33-41"},"PeriodicalIF":2.7,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S7527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30330283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells. 抗hsp90药物17AAG对人肿瘤细胞线粒体畸形的影响。

IF 2.7

Drug Target Insights Pub Date : 2011-01-01 Epub Date: 2011-06-07 DOI: 10.4137/DTI.S6582

Chaturvedi Vishal, Jonnala Ujwal Kumar, Cherukuvada Veera Brahmendra Swamy, Rangaraj Nandini, Gunda Srinivas, Rathinam Kumaresan, Singh Shashi, Amere Subbarao Sreedhar

{"title":"Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells.","authors":"Chaturvedi Vishal, Jonnala Ujwal Kumar, Cherukuvada Veera Brahmendra Swamy, Rangaraj Nandini, Gunda Srinivas, Rathinam Kumaresan, Singh Shashi, Amere Subbarao Sreedhar","doi":"10.4137/DTI.S6582","DOIUrl":"https://doi.org/10.4137/DTI.S6582","url":null,"abstract":"Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"5 ","pages":"11-32"},"PeriodicalIF":2.7,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S6582","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30111989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

The effect of valproic Acid on mesenchymal pluripotent cell proliferation and differentiation in extracellular matrices. 丙戊酸对细胞外基质间充质多能细胞增殖和分化的影响。

IF 2.7

Drug Target Insights Pub Date : 2011-01-01 Epub Date: 2011-03-22 DOI: 10.4137/DTI.S6534

Yuji Hatakeyama, Junko Hatakeyama, Atsushi Takahashi, Kyoko Oka, Eichi Tsuruga, Tetsuichiro Inai, Yoshihiko Sawa

{"title":"The effect of valproic Acid on mesenchymal pluripotent cell proliferation and differentiation in extracellular matrices.","authors":"Yuji Hatakeyama, Junko Hatakeyama, Atsushi Takahashi, Kyoko Oka, Eichi Tsuruga, Tetsuichiro Inai, Yoshihiko Sawa","doi":"10.4137/DTI.S6534","DOIUrl":"https://doi.org/10.4137/DTI.S6534","url":null,"abstract":"Valproic acid (2-n-propylpentanoic acid, VPA) is a widely used antiepileptic and anticonvulsant drug. Previous studies have reported that VPA effects osteogenesis in vivo and in vitro, yet it remains unclear whether VPA promotes cell differentiation of osteoblasts derived from mesenchymal cells. The purpose of this study was to clarify the effect of VPA on undifferentiated pluripotent mesenchymal cell proliferation and differentiation into osteoblasts while analyzing the impact of the absence or presence of extracellular matrices (ECMs). Mouse mesenchymal cells were cultured on non-coated plastic, type I collagen-coated, and fibronectin-coated plates in the absence or presence of VPA. A cell proliferation assay was performed in which modified formazan dye content was analyzed and proliferation nuclear antigen (PCNA)-positive cells were counted at various concentrations of VPA. A high concentration of VPA did not clearly alter cell morphology, but large numbers of stress fibers were observed in these cells and the cell proliferation ratio was decreased with positive PCNA counts. In the presence of matrices, the cell proliferation ratio decreased at low VPA concentrations compared with the ratio obtained in the absence of these ECMs. On the other hand, VPA promoted osteoblastic differentiation in the presence of type I collagen. These findings indicate that for undifferentiated mesenchymal cells, VPA promotes a decrease in the cell proliferation rate in the presence of ECMs and promotes osteoblastic differentiation, both of which could provide insight into additional mechanisms of osteoblastic cell differentiation caused by VPA.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"5 ","pages":"1-9"},"PeriodicalIF":2.7,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S6534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30129511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

A Model for NAD(P)H:Quinoneoxidoreductase 1 (NQO1) Targeted Individualized Cancer Chemotherapy. NAD(P)H:醌氧化还原酶1 (NQO1)靶向个体化肿瘤化疗模型

IF 2.7

Drug Target Insights Pub Date : 2009-01-01 Epub Date: 2009-01-15 DOI: 10.4137/dti.s1146

Asher Begleiter, Nadia El-Gabalawy, Laurie Lange, Marsha K Leith, Lynn J Guziec, Frank S Guziec

{"title":"A Model for NAD(P)H:Quinoneoxidoreductase 1 (NQO1) Targeted Individualized Cancer Chemotherapy.","authors":"Asher Begleiter, Nadia El-Gabalawy, Laurie Lange, Marsha K Leith, Lynn J Guziec, Frank S Guziec","doi":"10.4137/dti.s1146","DOIUrl":"https://doi.org/10.4137/dti.s1146","url":null,"abstract":"NQO1 (NAD(P)H:quinoneoxidoreductase 1) is a reductive enzyme that is an important activator of bioreductive antitumor agents. NQO1 activity varies in individual tumors but is generally higher in tumor cells than in normal cells. NQO1 has been used as a target for tumor specific drug development. We investigated a series of bioreductive benzoquinone mustard analogs as a model for NQO1 targeted individualized cancer chemotherapy. We compared the tumor cell growth inhibitory activity of benzoquinone mustard analogs with sterically bulky groups of different size and placed at different positions on the benzoquinone ring, using tumor cell lines with different levels of NQO1. We demonstrated that functional groups of different steric size could be used to produce a series of bioreductive antitumor agents that were activated by different levels of NQO1 in tumor cells. This series of drugs could then be used to target cells with specific levels of NQO1 for growth inhibition and to avoid damage to normal cells, like bone marrow cells, that have low levels of NQO1. This approach could be used to develop new bioreductive antitumor agents for NQO1 targeted individualized cancer chemotherapy.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"4 ","pages":"1-8"},"PeriodicalIF":2.7,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/dti.s1146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30129510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Targeting Insulin-Like Growth Factor-1 Signaling into the Central Nervous System for Promoting Myelin Repair 靶向胰岛素样生长因子-1信号进入中枢神经系统促进髓磷脂修复

IF 2.7

Drug Target Insights Pub Date : 2008-01-01 DOI: 10.4137/DTI.S362

N. Wilczak, J. De Keyser, D. Chesik

{"title":"Targeting Insulin-Like Growth Factor-1 Signaling into the Central Nervous System for Promoting Myelin Repair","authors":"N. Wilczak, J. De Keyser, D. Chesik","doi":"10.4137/DTI.S362","DOIUrl":"https://doi.org/10.4137/DTI.S362","url":null,"abstract":"Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). Without myelin, nerve impulses in the CNS are slowed or stopped, leading to a constellation of neurological symptoms. Demyelination also provides a permitting condition for irreversible axonal damage. Remyelination of MS lesions largely fails, although oligodendrocyte precursors and premyelinating oligodendrocytes (myelin forming cells) are present in many demyelinated plaques. Insulin-like growth factor (IGF)-1 is a growth factor that should provide the appropriate signals to promote repair of MS lesions, because it acts as a survival factor for cells of the oligodendrocyte lineage and stimulates myelin synthesis. In a pilot study on MS patients, no detectable remyelinating effects in the CNS were observed following subcutaneous administration of IGF-1. A number of reasons might explain a lack of beneficial effects: a) it is unlikely that subcutaneous administration of IGF-1 provides sufficient passage across the blood-brain-barrier and into the CNS, b) the biological actions of IGF-1 are tightly regulated by several insulin-like growth factor binding proteins (IGFBPs), which become upregulated in the demyelinated lesions and may prevent access of IGF-1 to its receptor, c) IGF-1 not only acts on oligodendrocytes, but also stimulates the proliferation of astrocytes, which form the glial scar that impedes repair processes. In this review, we will discuss strategies to enhance IGF-1 signaling in the CNS utilizing a) alternative routes of administration, b) IGF analogues that displace IGF-1 from regulatory IGFBPs and c) strategies to selectively target IGF-1 to oligodendrocytes.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"3 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S362","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70698237","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: 3

Therapies to Increase ApoA-I and HDL-Cholesterol Levels 提高apoa - 1和高密度脂蛋白胆固醇水平的疗法

IF 2.7

Drug Target Insights Pub Date : 2008-01-01 DOI: 10.4137/DTI.S447

W. M. Brown, Fabrizio S. Chiacchia

{"title":"Therapies to Increase ApoA-I and HDL-Cholesterol Levels","authors":"W. M. Brown, Fabrizio S. Chiacchia","doi":"10.4137/DTI.S447","DOIUrl":"https://doi.org/10.4137/DTI.S447","url":null,"abstract":"Cholesterol is transported around the body in the form of lipoprotein (lipid/protein) complexes, because it is almost insoluble in water. High-density lipoprotein (HDL) particles transport cholesterol from tissues back to the liver for excretion. Epidemiological studies have shown an inverse relationship between blood levels of HDL-cholesterol (HDL-c) and the incidence of clinically significant atherosclerosis. The beneficial effects of HDL in altering atherosclerotic disease are believed to involve elevated levels of HDL enhancing the efflux of cholesterol from arterial walls, increasing transport of cholesterol from arteries to the liver for excretion. This reverse cholesterol transport (RCT) pathway is used to explain both HDL's role in lipid metabolism and the inverse association between HDL-c plasma concentration and the risk of cardiovascular disease. Based on the RCT model, ApoA-I is an attractive target for therapeutic intervention. Experimental manipulations to increase production of ApoA-I have been associated with reduced atherogenicity. There is a continuing need for novel therapies that increase the biosynthesis of HDL, to inhibit the progression of and even bring about regression of atherosclerosis. Small molecule compounds that increase the production of endogenous ApoA-I would be attractive therapeutic agents for treating dyslipidemias.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"3 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70699280","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: 3

Memantine: Reality and Potentiality 美金刚:现实与潜力

IF 2.7

Drug Target Insights Pub Date : 2008-01-01 DOI: 10.4137/DTI.S622

R. Moretti, P. Torre, C. Vilotti, D. Manganaro, Luca Zanet, R. Antonello

引用次数: 1

Evidence of a Novel Gene from Aeromonas hydrophila Encoding a Putative Siderophore Receptor Involved in Bacterial Growth and Survival 嗜水气单胞菌新基因编码铁载体受体参与细菌生长和存活的证据

IF 2.7

Drug Target Insights Pub Date : 2008-01-01 DOI: 10.4137/DTI.S634

S. D. Tsen

引用次数: 0

The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors 非整合素血小板胶原受体化学合成肽的毒性研究

IF 2.7

Drug Target Insights Pub Date : 2008-01-01 DOI: 10.4137/DTI.S903

T. Chiang, V. Woo-Rasberry

{"title":"The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors","authors":"T. Chiang, V. Woo-Rasberry","doi":"10.4137/DTI.S903","DOIUrl":"https://doi.org/10.4137/DTI.S903","url":null,"abstract":"A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryo-blastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"3 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70699694","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: 0

Recent Advancements in Targeted Delivery of Therapeutic Molecules in Neurodegenerative Disease–-Spinocerebellar Ataxia–-Opportunities and Challenges 神经退行性疾病治疗分子靶向递送的最新进展——脊髓小脑共济失调——机遇与挑战

IF 2.7

Drug Target Insights Pub Date : 2008-01-01 DOI: 10.4137/DTI.S378

S. Prakash, M. Malhotra

{"title":"Recent Advancements in Targeted Delivery of Therapeutic Molecules in Neurodegenerative Disease–-Spinocerebellar Ataxia–-Opportunities and Challenges","authors":"S. Prakash, M. Malhotra","doi":"10.4137/DTI.S378","DOIUrl":"https://doi.org/10.4137/DTI.S378","url":null,"abstract":"Drug discovery and its methodologies have been very effective in terms of treating cancers and immunological disorders but have not been able to stop genetic diseases as most of the drugs target at the protein level. They merely mitigate the symptoms of the disease. Spinocerebellar ataxia is a neurological genetic disorder that is caused by the formation of an abnormal protein. There have been several reports on ataxic drug development but actual clinical treatment is yet to be achieved. Oligonucleotide therapy called sequence specific siRNA mediated gene silencing has evolved with promising results. This approach emphasizes on suppressing the expression of the diseased gene at mRNA level. However, there is a limitation in delivery of siRNA to the target site. Several methods have been developed over the last decade to enhance the target specific delivery of DNA, siRNA, protein and small drug molecules for therapeutic purpose with less or no side effects. This review discusses the latest upcoming technologies in the field that focus on a number of nonviral nanocarriers for targeted delivery. In this review, we explore the promise and potential of novel therapeutics with interest on ataxia therapy.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"3 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/DTI.S378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70698300","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: 3