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Current Pharmaceutical Design

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https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#1
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#2
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714417/molecular-targeting-of-erks-rsk2-signaling-in-cancers
#3
Yong-Yeon Cho
Accumulating studies have provided concrete evidence that p90 ribosomal S6 kinase 2 (RSK2) is a key signaling molecule involved in cell proliferation, transformation, and cancer development. RSK2 is known to be an etiological gene of Coffin-Lowry Syndrome (CLS). Recently, signaling analysis and molecular biological approaches have provided concrete evidence that RSK2 plays an essential role in human cancers. Here, we will extensively discuss signaling pathways regulating RSK2 activity, the role of RSK2 in human cancer development, inhibitors suppressing RSK2 activity, and why RSK2 is an important target to develop drugs for human cancers...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714416/application-of-kinase-inhibitors-for-anti-aging-intervention
#4
Mercedes Cano, Antonio Ayala, Francesco Marotta, Sandro Argüelles
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives . Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review , we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714415/aquaporin-4-in-astrocytes-is-a-target-for-therapy-in-alzheimer-s-disease
#5
Yu-Long Lan, Jian-Jiao Chen, Gang Hu, Jun Xu, Ming Xiao, Shao Li
Current experimental evidence points to the conclusion that aquaporin 4 (AQP4), which is an important water-channel membrane protein found in the brain, could play major roles in various brain conditions pathologically including pathogenesis of Alzheimer's disease (AD). In this paper, we review how AQP4 and altered astrocyte functions interact in AD, and provide experimental evidence highlighting the importance of this topic for the future investigations. The interactions of AQP4 are as follows: (i) AQP4 could influence astrocytic calcium signaling and potassium homeostasis...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714414/role-of-mirna-in-lung-cancer-potential-biomarkers-and-therapies
#6
Xiaohong Du, Jitai Zhang, Juping Wang, Xiaoming Lin, Feng Ding
MicroRNAs (miRNAs) are small noncoding RNAs, which downregulate gene expression by repressing or degrading mRNA targets. Lung cancer (LC), together with liver and colorectal cancers are the three leading causes of cancer death worldwide, and 80% of LCs belong to non-small cell lung cancers (NSCLCs). Despite a great advancement in developing distinct and delicate tools for early diagnosis and targeted therapies over the last decade, only about 15% of the NSCLC patients eventually survived. MiRNAs are frequently dysregulated in carcinoma, including LC...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714413/mirna-based-therapeutics-for-lung-cancer
#7
Miaowei Wu, Guosheng Wang, Wei Tian, Yongchuan Deng, Yibing Xu
BACKGROUND: miRNA, a small non-coding RNA molecule containing about 22 nucleotides, functions in RNA silencing and post-transcriptional regulation of gene expression. With these qualities, miRNAs modulate multiple signaling pathways involved in cancer development, such as cellular proliferation, apoptosis, and migration. METHODS: The goal of this review is to discuss possible miRNAs-based therapeutic strategies, through defining performance of miRNAs in carcinogenesis, in particular in lung cancer...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714412/regulation-mechanism-of-micrornas-in-non-small-cell-lung-cancer
#8
Feng-Yun Gong, Tao Bai, Ding-Yu Zhang, Chao-Lin Huang, Jing Lv, Jing-Li Wang, Xu-Dong Hu, Juan Wang, Wei Liu
MicroRNAs are small non-coding RNAs with regulatory biological activity, by modulating target genes on epigenetic, transcriptional, post-transciptional and translational levels. Hundreds of reports indicated that miRNAs play important roles in non-small cell lung cancer (NSCLC). Actually, microRNAs are both regulation targets and regulators targeting effector genes. This article reviewed multifaceted role of microRNAs associated to NSCLC, not only targeting to but also targeted by tumor related genes, to help us understand microRNAs related complex regulation networks...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714411/pharmacology-and-literature-review-based-on-related-death-and-non-fatal-case-reports-of-the-benzofurans-and-benzodifurans-designer-drugs
#9
Bernardino Barceló Martín, Isabel Gomila
BACKGROUND: Benzofurans and benzodifurans are two groups of psychoactive substances that had originally been synthesized for research purpose. Benzofurans' structure is quite similar to the known recreational drug 3,4-methylenedioxymethamphetamine together with its active metabolite 3,4-methylenedioxyamphetamine. Benzodifurans are closely related to phenethylamines, but have more hallucinogens effects and much longer duration of action. This study aims to review the accessible evidence-based literature on benzofurans and benzodifurans pharmacology and toxicology...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714410/management-of-blood-pressure-and-heart-rate-in-patients-with-acute-stroke
#10
Carlo Maida, Antonino Tuttolomondo, Domenico Di Raimondo, Antonio Pinto
BACKGROUND: Stroke represent one of the most devastating of all neurological diseases, affecting about 15 million people per year and is an important cause of morbidity and mortality worldwide and currently the leading cause of adult disability in developed countries. Blood pressure and heart rate may undergo several modifications in patients with both ischemic and hemorrhagic stroke in fact raised blood pressure levels may lead to cerebral edema, hematoma expansion or hemorrhagic transformation and in contrast low blood pressure can lead to increased cerebral infarction or perihematomal ischemia...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714407/update-of-standard-practices-for-new-method-validation-in-forensic-toxicology
#11
Sarah M R Wille, Wim Coucke, Thierry De Baere, Frank T Peters
: International agreement concerning validation guidelines is important as reporting reliable analytical data is the backbone of forensic bioanalytical research and applications. Guidelines such as those provided by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), the German speaking Gesellschaft für Toxikologie und Forensische Chemie (GTFCH) and the Scientific Working Group of Forensic Toxicology (SWGTOX) provide a standard for fundamental validation parameters such as selectivity, matrix effects, method limits, calibration, accuracy and stability, as well as other parameters such as carryover, dilution integrity and incurred sample reanalysis...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714406/role-of-the-immune-component-of-tumor-microenvironment-in-the-efficiency-of-cancer-treatment-perspectives-for-the-personalized-therapy
#12
Marina Stakheyeva, Vladimir Riabov, Irina Mitrofanova, Nikolai Litviakov, Evgeny Choynzonov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714405/emerging-targets-to-relieve-fat-stress-induced-liver-diseases-udca-tocotrienol-%C3%AF-3-pufas-and-igy-targeted-npc1l1-cholesterol-transporter
#13
Ji-Young Cha, Jong-Min Park, Ho-Jae Lee, Jin-Sik Bae, Young-Min Han, Byung-Chul Oh, Kwang Hyun Ko, Ki-Baik Hahm
Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to non-alcoholic steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714404/current-and-emerging-strategies-in-osteoporosis-management
#14
Stefka Ivanova, Liliya Vasileva
The abnormal loss of bone tissue is defined as osteoporosis. Increased risk of fractures, low bone mineral density (BMD) and loss of the structural and biomechanical properties of the bone tissue characterize this pathological condition. Physiologically bone undergoes a continuous remodeling process involving balance between the activity of osteoblast and osteoclast. Disruption in this balanced condition increases the risk of osteoporosis. Both sexes are affected, but with higher prevalence in women after menopause...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714403/gsk3-inhibitors-in-the-therapeutic-development-of-diabetes-cancer-and-neurodegeneration-past-present-and-future
#15
Mudasir Maqbool, Nasimul Hoda
GSK3 has gained a considerable attention of researchers in the late 1970s as an inevitable drug target to treat diabetes. Furthermore, it was found to have a key role in the development of diseases like cancer and neurodegeneration (ND). A broad spectrum of GSK3 inhibitors have been discovered from time to time in order to curb these diseases. Inhibition of GSK3 by insulin boosts the dephosphorylation of glycogen synthase, hence its activation to convert UDP glucose into glycogen. Lack of insulin and insulin-resistance is supposed to be the cause of type 2 diabetes (Diabetes mellitus)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714409/ampk-therapeutic-target-for-diabetes-and-cancer-prevention
#16
Shotaro Umezawa, Takuma Higurashi, Atsushi Nakajima
BACKGROUND: AMP-activated protein kinase (AMPK) is a protein kinase that maintains homeostasis in cells and organs. As a master regulator of metabolism, AMPK coordinates many metabolic reactions. AMPK is a key factor in diabetes and metabolic syndrome associated with dysregulation of the metabolic status. Recently, AMPK has also attracted attention as a tumor suppressor. The aim of this article is to discuss about the role of AMPK in diabetes as well as cancer and to evaluate its effectiveness in treatment and prevention of these diseases...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714408/biomaterials-and-supercritical-fluid-technologies-which-perspectives-to-fabricate-artificial-extracellular-matrix
#17
Della Porta Giovanna, E Reverchon, N Maffulli
The foundation of tissue engineering for either therapeutic or diagnostic applications is the ability to exploit living cells. Tissue engineering utilizes living cells as engineering materials implanted, seeded or bio-plotted into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called scaffolds, are critical, both ex vivo and in vivo, to influence their own microenvironments. Scaffolds can serve the following purposes: allow cell attachment and migration, deliver and retain cells and biochemical factors, enable diffusion of vital cell nutrients or expressed products, exert certain mechanical and biological influences to modify the behaviour of the cell phase...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28707576/new-strategies-for-the-prevention-and-treatment-of-systemic-and-local-bone-loss-from-pathophysiology-to-clinical-application
#18
A Fassio, Maurizio Rossini, Ombretta Viapiana, Luca Idolazzi, Camilla Benini, Elisabetta Vantaggiato, Davide Gatti
Bone loss is the result of a negative unbalance between bone formation ad bone resorption. In the last years, the studies on the Wnt canonical pathway have highlighted its crucial role in bone balance through its influence on the activity and maturation of the osteoblast line and in the Receptor Activator of Nuclear Factor κ B (RANK) - RANK ligand (RANKL)/Osteoprotegerin (OPG) system. These mechanisms are involved not only in the pathological processes inducing not only systemic bone loss (ie. Postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, etc...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28699538/virtual-screening-and-statistical-analysis-in-the-design-of-new-caffeine-analogues-molecules-with-potential-epithelial-anticancer-activity
#19
Josivan da Silva Costa, Karina Da Silva Lopes Costa, Josiane Viana Cruz, Ryan da Silva Ramosb, Luciane Barros Silva, Davi Do Socorro Barros Brasilc, Carlos Henrique Tomich de Paula da Silva, Cleydson Breno Rodrigues Dos Santos, Williams Jorge da Cruz Macêdoe
About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the world health organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity...
July 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28699540/dna-base-excision-repair-the-achilles-heel-of-tumour-cells-and-their-microenvironment
#20
M Poletto, A J Legrand, G L Dianov
Our current understanding of cancer suggests that every tumour has individual features. Approaches to cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system that is responsible for maintaining genome integrity. The BER pathway prevents the occurrence of disease, including cancer, by constantly repairing DNA base lesions and DNA single strand breaks caused by endogenous and exogenous mutagens...
July 10, 2017: Current Pharmaceutical Design
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