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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/28911826/immunoproteasome-selective-and-non-selective-inhibitors-a-promising-approach-for-the-treatment-of-multiple-myeloma
#1
REVIEW
Roberta Ettari, Maria Zappalà, Silvana Grasso, Caterina Musolino, Vanessa Innao, Alessandro Allegra
The ubiquitin-proteasome system (UPS) is the major non-lysosomal proteolytic system for the degradation of abnormal or damaged proteins no longer required. The proteasome is involved in degradation of numerous proteins which regulate the cell cycle, indicating a role in controlling cell proliferation and maintaining cell survival. Defects in the UPS can lead to anarchic cell proliferation and to tumor development. For these reasons UPS inhibition has become a significant new strategy for drug development in cancer treatment...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28911825/paving-the-rho-in-cancer-metastasis-rho-gtpases-and-beyond
#2
REVIEW
Sepp Jansen, Reinoud Gosens, Thomas Wieland, Martina Schmidt
Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28882537/bevacizumab-induced-hypertension-clinical-presentation-and-molecular-understanding
#3
REVIEW
Megan Li, Deanna L Kroetz
Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment...
September 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28867452/the-role-of-osteoprotegerin-in-the-crosstalk-between-vessels-and-bone-its-potential-utility-as-a-marker-of-cardiometabolic-diseases
#4
REVIEW
Luc Rochette, Alexandre Meloux, Eve Rigal, Marianne Zeller, Yves Cottin, Catherine Vergely
Among the numerous molecules that are being studied for their potential utility as biomarkers of cardiovascular diseases, much interest has been shown in the superfamily of tumor necrosis factor (TNF) receptors. Members of this family include osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). These signals may be expressed and regulated, and their functions could be involved in several physiological and pathological processes...
September 1, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28847562/cannabis-use-during-pregnancy-pharmacokinetics-and-effects-on-child-development
#5
REVIEW
Kimberly S Grant, Rebekah Petroff, Nina Isoherranen, Nephi Stella, Thomas M Burbacher
The broad-based legalization of cannabis use has created a strong need to understand its impact on human health and behavior. The risks that may be associated with cannabis use, particularly for sensitive subgroups such as pregnant women, are difficult to define because of a paucity of dose-response data and the recent increase in cannabis potency. Although there is a large body of evidence detailing the mode of action of Δ(9)-tetrahydrocannabinol (THC) in adults, little work has focused on understanding how cannabis use during pregnancy may impact the development of the fetal nervous system and whether additional plant-derived cannabinoids might participate...
August 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28847561/non-canonical-function-of-tat-in-regulating-host-microtubule-dynamics-implications-for-the-pathogenesis-of-lentiviral-infections
#6
REVIEW
Min Liu, Xin Du, Jun Zhou
Lentiviruses are a class of genetically unique retroviruses that share similar features, despite their wide variety of host species. Transactivator of transcription (Tat) proteins of lentiviruses are critical for the regulation of viral transcription and replication. Recent studies demonstrate that in addition to mediating transactivation, Tat binds to the microtubule cytoskeleton of the host cell and interferes with microtubule dynamics, ultimately triggering apoptosis. This non-canonical function of Tat appears to be critical for the pathogenesis of lentiviral diseases, such as acquired immunodeficiency syndrome...
August 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28842272/pharmacotherapeutic-potential-of-ginger-and-its-compounds-in-age-related-neurological-disorders
#7
REVIEW
Jin Gyu Choi, Sun Yeou Kim, Minsun Jeong, Myung Sook Oh
Age-related neurological disorders (ANDs), including neurodegenerative diseases, are multifactorial disorders with a risk that increases with aging. ANDs are generally characterized by common neuropathological conditions of the central nervous system, such as oxidative stress, neuroinflammation, and protein misfolding. Recently, efforts have been made to overcome ANDs because of the increase in age-dependent prevalence. Ginger, the rhizome of Zingiber officinale Roscoe, is a popular food spice and has a long history of use in traditional medicine for treating various disease symptoms...
August 24, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28842273/oxidative-stress-and-cellular-pathways-of-asthma-and-inflammation-therapeutic-strategies-and-pharmacological-targets
#8
REVIEW
Vikas Mishra, Jaspreet Banga, Patricia Silveyra
Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways...
August 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28834699/t-cell-engaging-bispecific-antibody-t-bsab-from-technology-to-therapeutics
#9
REVIEW
Zhihao Wu, Nai-Kong V Cheung
Harnessing the power of the human immune system to treat cancer is the essence of immunotherapy. Monoclonal antibodies engage the innate immune system to destroy targeted cells. For the last 30years, antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity have been the main mechanisms of anti-tumor action of unconjugated antibody drugs. Efforts to exploit the potentials of other immune cells, in particular T cells, culminated in the recent approval of two T cell engaging bispecific antibody (T-BsAb) drugs, thereby stimulating new efforts to accelerate similar platforms through preclinical and clinical trials...
August 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28834698/emt-mechanisms-and-therapeutic-implications
#10
REVIEW
Mohini Singh, Nicolas Yelle, Chitra Venugopal, Sheila K Singh
Metastasis, the dissemination of cancer cells from primary tumors, represents a major hurdle in the treatment of cancer. The epithelial-mesenchymal transition (EMT) has been studied in normal mammalian development for decades, and it has been proposed as a critical mechanism during cancer progression and metastasis. EMT is tightly regulated by several internal and external cues that orchestrate the shifting from an epithelial-like phenotype into a mesenchymal phenotype, relying on a delicate balance between these two stages to promote metastatic development...
August 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28830841/molecular-pathogenesis-and-therapeutic-implications-in-pediatric-high-grade-gliomas
#11
REVIEW
Tareq A Juratli, Nan Qin, Daniel P Cahill, Mariella G Filbin
High-grade gliomas (HGG) are the most common malignant brain tumors in the pediatric population and account for a large subset of all pediatric central nervous system neoplasms. The management of pediatric HGG continues to be challenging, with poor outcome in many cases despite aggressive treatments. Consequently, parallel research efforts have been focused on identifying the underlying genetic and biological basis of pediatric HGG in order to more clearly define prognostic subgroups for treatment stratification as well as identify new treatment targets...
August 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28830840/binge-eating-disorder-clinical-and-therapeutic-advances
#12
REVIEW
Peter H Hutson, Iris M Balodis, Marc N Potenza
Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology and pharmacology, drawing from clinical therapeutic, neuroimaging, cognitive, human genetic and animal model studies. These studies, which are still in their infancy, indicate that while there are many gaps in our knowledge, several key neural substrates appear to underpin binge-eating and may be conserved between human and animals...
August 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28830839/the-potential-for-targeted-rewriting-of-epigenetic-marks-in-copd-as-a-new-therapeutic-approach
#13
REVIEW
Dan-Dan Wu, Juan Song, Sabine Bartel, Susanne Krauss-Etschmann, Marianne G Rots, Machteld N Hylkema
Chronic obstructive pulmonary disease (COPD) is an age and smoking related progressive, pulmonary disorder presenting with poorly reversible airflow limitation as a result of chronic bronchitis and emphysema. The prevalence, disease burden for the individual, and mortality of COPD continues to increase, whereas no effective treatment strategies are available. For many years now, a combination of bronchodilators and anti-inflammatory corticosteroids has been most widely used for therapeutic management of patients with persistent COPD...
August 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28830838/members-of-fox-family-could-be-drug-targets-of-cancers
#14
REVIEW
Jinhua Wang, Wan Li, Ying Zhao, De Kang, Weiqi Fu, Xiangjin Zheng, Xiaocong Pang, Guanhua Du
FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end.
August 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28827151/endothelial-and-cardiac-progenitor-cells-for-cardiovascular-repair-a-controversial-paradigm-in-cell-therapy
#15
REVIEW
Vanessa Bianconi, Amirhossein Sahebkar, Petri Kovanen, Francesco Bagaglia, Biagio Ricciuti, Paolo Calabrò, Giuseppe Patti, Matteo Pirro
Stem cells have the potential to differentiate into cardiovascular cell lineages and to stimulate tissue regeneration in a paracrine/autocrine manner; thus, they have been extensively studied as candidate cell sources for cardiovascular regeneration. Several preclinical and clinical studies addressing the therapeutic potential of endothelial progenitor cells (EPCs) and cardiac progenitor cells (CPCs) in cardiovascular diseases have been performed. For instance, autologous EPC transplantation and EPC mobilization through pharmacological agents contributed to vascular repair and neovascularization in different animal models of limb ischemia and myocardial infarction...
August 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28827150/the-role-of-the-leukemia-inhibitory-factor-receptor-in-neuroprotective-signaling
#16
REVIEW
Stephanie M Davis, Keith R Pennypacker
Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190kDa subunit couples with the 130kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison...
August 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28821397/cardiac-metabolism-a-promising-therapeutic-target-for-heart-failure
#17
REVIEW
Hannah Noordali, Brodie L Loudon, Michael P Frenneaux, Melanie Madhani
Heart failure, with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), is associated with high morbidity and mortality. Although many established pharmacological interventions exist for those patients with HFrEF, hospitalization and death rates remain high, and in those with HFpEF (over half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced metabolic capacity for carbohydrates and fatty acids, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced...
August 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28757156/emerging-understanding-of-the-mechanism-of-action-of-bronchial-thermoplasty-in-asthma
#18
REVIEW
J N S d'Hooghe, N H T Ten Hacken, E J M Weersink, P J Sterk, J T Annema, P I Bonta
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...
July 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28757155/antibody-drug-conjugates-for-treatment-of-breast-cancer-novel-targets-and-diverse-approaches-in-adc-design
#19
REVIEW
Pamela A Trail, Gene M Dubowchik, Timothy B Lowinger
Breast cancer is a heterogeneous group of malignancies with a spectrum of molecular subtypes, pathologies and outcomes that together comprise the most common non-cutaneous cancer in women. Currently, over 80% of breast cancer patients are diagnosed at relatively early stages of disease where there are encouraging data on outcomes and long term survival. However, there is currently no curative option for those patients with metastatic disease and there is a substantial medical need to identify effective and safe treatment options for these patients...
July 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28757154/the-central-serotonin2b-receptor-as-a-new-pharmacological-target-for-the-treatment-of-dopamine-related-neuropsychiatric-disorders-rationale-and-current-status-of-research
#20
REVIEW
Céline Devroye, Adeline Cathala, Pier Vincenzo Piazza, Umberto Spampinato
The serotonin2B receptor (5-HT2BR), which was first cloned and characterized in the rat stomach fundus, is the most recent addition to the 5-HT2R family. While its involvement in the regulation of gastrointestinal, vascular, pulmonary and cardiac physiology has been widely investigated, its functional role within the central nervous system (CNS) has received much less attention. Nevertheless, when considering the data available in the literature with regards to the regulatory control exerted by the central 5-HT2BR on dopamine (DA) and serotonin (5-HT) neuron activity, a very interesting picture emerges and highlights the key role of these receptors for future therapeutic strategies of DA-related neuropsychiatric disorders...
July 27, 2017: Pharmacology & Therapeutics
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