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Current Pharmacology Reports

Rakshamani Tripathi, Zulong Liu, Rina Plattner
Purpose of Review: The goal of this review is to summarize our current knowledge regarding how ABL family kinases are activated in solid tumors and impact on solid tumor development/progression, with a focus on recent advances in the field. Recent Findings: Although ABL kinases are known drivers of human leukemia, emerging data also implicates the kinases in a large number of solid tumor types where they promote diverse processes such as proliferation, survival, cytoskeletal reorganization, cellular polarity, EMT (epithelial-mesenchymal-transition), metabolic reprogramming, migration, invasion and metastasis via unique signaling pathways...
October 2018: Current Pharmacology Reports
Benjamin L Woolbright, Hartmut Jaeschke
Purpose of Review: This article provides a brief overview of mechanisms of inflammatory liver injury and how this applies to drug hepatotoxicity with a particular emphasis on the role of inflammation in acetaminophen-induced liver injury. Recent Findings: Significant progress has been made in the last decade in our understanding of the initiation of sterile inflammation after necrotic cell death by the release of damage-associated molecular patterns and their recognition by toll-like receptors and others on macrophages...
October 2018: Current Pharmacology Reports
Gaurav Kumar, Mudassir Farooqui, Chinthalapally V Rao
Purpose of review: This article provides a brief overview of cancer-preventive phytochemicals specifically targeting pancreatic cancer (PC) stem cells for prevention and treatment. Recent findings: Cancer stem cells (CSCs) represent a small proportion of the total cells of a given tumor, and contribute to tumor growth, recurrence, metastasis, and treatment resistance. Many intertwined pathways, including hedgehog, Wnt Signaling, and NOTCH, have been shown to play a role in the formation of CSCs...
August 2018: Current Pharmacology Reports
Yijing Zhou, Fengping Dong, Yingwei Mao
Purpose of Review: This review summarizes recent studies on the molecular mechanisms of RNA binding proteins (RBPs) that control neurological functions and pathogenesis in various neurodevelopmental and neurodegenerative diseases, including autism spectrum disorders, schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and spinocerebellar ataxia. Recent Findings: RBPs are critical players in gene expression that regulate every step of posttranscriptional modifications...
August 2018: Current Pharmacology Reports
Lei Diao, Bernd Meibohm
Purpose of review: Monoclonal antibodies targeting key checkpoints in immune stimulatory pathways have over the last years become the mainstay of cancer immunotherapy. This article provides a brief review of the application and key impact of pharmacometrics and quantitative clinical pharmacology approaches in the development of these novel biologics. Recent findings: The clinical development and selection of optimal dosing regimens for monoclonal antibodies used in immune-oncology has been facilitated by an extensive application of pharmacometric approaches to characterize the exposure-response relationship for major efficacy and safety endpoints...
August 2018: Current Pharmacology Reports
Yifan Bao, Xiaochao Ma, Theodore P Rasmussen, Xiao-Bo Zhong
Purpose of this Review: In order to combat the development of drug resistance, the clinical treatment of tuberculosis requires the combined use of several anti-tuberculosis (anti-TB) drugs, including isoniazid and rifampicin. Combinational treatment approaches are suggested by the World Health Organization (WHO) and are widely accepted throughout the world. Unfortunately, a major side effect of the treatment is the development of anti-tuberculosis drug-induced liver injury (AT-DILI). Many factors contribute to isoniazid- and rifampicin-mediated AT-DILI and genetic variations are among the most common factors...
June 2018: Current Pharmacology Reports
Sujit Nair, Ah-Ng Tony Kong
Purpose of review: Although significant progress has been made in cancer research, there exist unmet needs in patient care as reflected by the 'Cancer Moonshot' goals. This review appreciates the potential utility of quantitative pharmacology in cancer precision medicine. Recent findings: Precision oncology has received federal funding largely due to 'The Precision Medicine Initiative'. Precision medicine takes into account the inter-individual variability, and allows for tailoring the right medication or the right dose of drug to the best subpopulation of patients who will likely respond to the intervention, thus enhancing therapeutic success and reducing "financial toxicity" to patients, families and caregivers...
June 2018: Current Pharmacology Reports
Almin I Lalani, Sining Zhu, Samantha Gokhale, Juan Jin, Ping Xie
Purpose of Review: This review presents an overview of the current knowledge of TRAF molecules in inflammation with an emphasis on available human evidence and direct in vivo evidence of mouse models that demonstrate the contribution of TRAF molecules in the pathogenesis of inflammatory diseases. Recent Findings: The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic proteins was initially identified as signaling adaptors that bind directly to the intracellular domains of receptors of the TNF-R superfamily...
February 2018: Current Pharmacology Reports
Awais Anwar, Emma Gould, Ryan Tinson, Javaid Iqbal, Chris Hamilton
Purpose of review: This article provides a brief overview of natural phytoprotective products of allium with a special focus on the therapeutic potential of diallyl polysulfanes from garlic, their molecular targets and their fate in the living organisms. A comprehensive overview of antimicrobial and anticancer properties of published literature is presented for the reader to understand the effective concentrations of polysulfanes and their sensitivity towards different human pathogenic microbes, fungi, and cancer cell lines...
2018: Current Pharmacology Reports
Rishil J Kathawala, Andrzej Kudelka, Basil Rigas
Purpose of Review: Ovarian cancer (OvCa) is the most lethal of all gynecological cancers, with a 5-year survival around 46%, mainly due to limitations in early diagnosis and treatment. Consequently, the chemoprevention of OvCa emerges as an important option to control this dismal disease. Here, we discuss the role of risk assessment in the design of chemoprevention strategies for OvCa, describe candidate agents, and assess future directions in this field. Recent Findings: OvCa chemoprevention represents an opportunity for all women, especially those at high risk such as carriers of BRCA1 or BRCA2 mutations...
2018: Current Pharmacology Reports
Yi Ching Esther Wan, Jiaxian Liu, Kui Ming Chan
Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in chromatin-modifying enzymes has long been implicated in cancers. More recently, recurrent histone mutations have been identified in multiple cancers and have been shown to impede histone methylation. All three histone mutations (H3K27M, H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a lysine residue that is a target of methylation...
2018: Current Pharmacology Reports
Yonghong Li, Victor Pham, Michelle Bui, Liankun Song, Chunli Wu, Arman Walia, Edward Uchio, Feng Smith-Liu, Xiaolin Zi
Purpose of review: Rhodiola rosea extracts have been used as a dietary supplement in healthy populations, including athletes, to non-specifically enhance the natural resistance of the body to both physical and behavior stresses for fighting fatigue and depression. We summarize the information with respect to the new pharmacological activities of Rhodiola rosea extracts and its underlying molecular mechanisms in this review article. Recent findings: In addition to its multiplex stress-protective activity, Rhodiola rosea extracts have recently demonstrated its anti-aging, anti-inflammation, immunostimulating, DNA repair and anti-cancer effects in different model systems...
December 2017: Current Pharmacology Reports
Ju Hwan Cho, Filiz Oezkan, Michael Koenig, Gregory A Otterson, James Gordon Herman, Kai He
Lung cancer is the leading cause of cancer-related death in the United States and worldwide. Novel therapeutic developments are critically necessary to improve outcomes for this disease. Aberrant epigenetic change plays an important role in lung cancer development and progression. Therefore, drugs targeting the epigenome are being investigated in the treatment of lung cancer. Monotherapy of epigenetic therapeutics such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) have so far not shown any apparent benefit while one of the clinical trials with the combinations of DNMTi and HDACi showed a small positive signal for treating lung cancer...
December 2017: Current Pharmacology Reports
Orchi Dutta, Jorge A Masso-Silva, Keyi Wang, Amariliz Rivera
No abstract text is available yet for this article.
December 2017: Current Pharmacology Reports
Amanda R Muñoz, Divya Chakravarthy, Jingjing Gong, Glenn A Halff, Rita Ghosh, Addanki P Kumar
Purpose of the review: The 5-year survival rate of patients with pancreatic cancer (PanCA) has remained stagnant. Unfortunately, the incidence is almost equal to mortality rates. These facts underscore the importance of concerted efforts to understand the pathology of this disease. Deregulation of multiple signaling pathways involved in a wide variety of cellular processes including proliferation, apoptosis, invasion, and metastasis contribute not only to cancer development but also to therapeutic resistance...
December 2017: Current Pharmacology Reports
Eswar Shankar, Aditi Goel, Karishma Gupta, Sanjay Gupta
Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4', 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases...
December 2017: Current Pharmacology Reports
Everett K Henry, Juan M Inclan-Rico, Mark C Siracusa
Purpose of Review: It is well established that T helper type 2 (TH 2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH 2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH 2 cell polarization...
December 2017: Current Pharmacology Reports
Madeleine D Hu, Karen L Edelblum
Purpose of review: Intestinal mucosal immunity is tightly regulated to ensure effective host defense against invasive microorganisms while limiting the potential for aberrant damage. In inflammatory bowel disease (IBD), an imbalance between effector and regulatory T cell populations results in an uncontrolled inflammatory response to commensal bacteria. Intraepithelial lymphocytes (IEL) are perfectly positioned within the intestinal epithelium to provide the first line of mucosal defense against luminal microbes or rapidly respond to epithelial injury...
December 2017: Current Pharmacology Reports
Eric K Kwong, Xiaojiaoyang Li, Phillip B Hylemon, Huiping Zhou
The ever-increasing prevalence of metabolic diseases such as dyslipidemia and diabetes in the western world continues to be of great public health concern. Biologically active sphingolipids, such as sphingosine 1-phosphate (S1P) and ceramide, are important regulators of lipid metabolism. S1P not only directly functions as an active intracellular mediator, but also activates multiple signaling pathways via five transmembrane G-protein coupled receptors (GPCRs), S1PR1-5. S1P is exclusively formed by sphingosine kinases (SphKs)...
August 2017: Current Pharmacology Reports
Zidong Donna Fu, Julia Yue Cui
Recent technological advancements including metagenomics sequencing and metabolomics have allowed the discovery of critical functions of gut microbiota in obesity, malnutrition, neurological disorders, asthma, and xenobiotic metabolism. Classification of the human gut microbiome into distinct "enterotypes" has been proposed to serve as a new paradigm for understanding the interplay between microbial variation and human disease phenotypes, as many organs are affected by gut microbiota modifications during the pathogenesis of diseases...
June 2017: Current Pharmacology Reports
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