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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/28442216/trem2-microglia-and-neurodegenerative-diseases
#1
REVIEW
Felix L Yeh, David V Hansen, Morgan Sheng
Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the US. The neuropathological hallmarks of the disease are extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau aggregates. Genetic variants of TREM2 (triggering receptor expressed on myeloid cells 2), a cell-surface receptor expressed selectively in myeloid cells, greatly increase the risk of AD, implicating microglia and the innate immune system as pivotal factors in AD pathogenesis...
April 22, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28427863/ros-in-cancer-the-burning-question
#2
REVIEW
Iok In Christine Chio, David A Tuveson
An unanswered question in human health is whether antioxidation prevents or promotes cancer. Antioxidation has historically been viewed as chemopreventive, but emerging evidence suggests that antioxidants may be supportive of neoplasia. We posit this contention to be rooted in the fact that ROS do not operate as one single biochemical entity, but as diverse secondary messengers in cancer cells. This cautions against therapeutic strategies to increase ROS at a global level. To leverage redox alterations towards the development of effective therapies necessitates the application of biophysical and biochemical approaches to define redox dynamics and to functionally elucidate specific oxidative modifications in cancer versus normal cells...
April 17, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28416139/cars-synthetic-immunoreceptors-for-cancer-therapy-and-beyond
#3
REVIEW
ZeNan L Chang, Yvonne Y Chen
Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide T cells with engineered specificity. Clinical success in treating B-cell malignancies has demonstrated the therapeutic potential of CAR-T cells against cancer, and efforts are underway to expand the use of engineered T cells to the treatment of diverse medical conditions, including infections and autoimmune diseases. Here, we review current understanding of the molecular properties of CARs, how this knowledge informs the rational design and characterization of novel receptors, the successes and shortcomings of CAR-T cells in the clinic, and emerging solutions for the continued improvement of CAR-T cell therapy...
April 13, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28408271/quid-pro-quo-a-tumor-is-not-alone
#4
EDITORIAL
Catarina Sacristán, David A Tuveson
No abstract text is available yet for this article.
April 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28400243/cancer-manipulation-of-host-physiology-lessons-from-pancreatic-cancer
#5
REVIEW
Constantinos P Zambirinis, George Miller
Homeostasis is a fundamental property of living organisms enabling the human body to withstand internal and external insults. In several chronic diseases, and especially in cancer, many homeostatic mechanisms are deranged. Pancreatic cancer in particular is notorious for its ability to invoke an intense fibroinflammatory stromal reaction facilitating its progression and resistance to treatment. In the past decade, several seminal discoveries have elucidated previously unrecognized modes of commandeering the host's defense systems...
April 8, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28396056/connecting-the-metabolic-and-immune-responses-to-cancer
#6
REVIEW
Thomas R Flint, Douglas T Fearon, Tobias Janowitz
Separate research fields have advanced our understanding of, on the one hand, cancer immunology and, on the other hand, cachexia, the fatal tumor-induced wasting syndrome. A link between the host's immune and metabolic responses to cancer remained unexplored. Emerging work in preclinical models of colorectal and pancreatic cancer has unveiled tumor-induced reprogramming of liver metabolism in cachexia that leads to suppression of antitumor immunity and failure of immunotherapy. As research efforts in metabolism and immunology in cancer are rapidly expanding, it is timely to discuss the metabolic and immunological determinants of the cancer-host interaction...
April 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28372922/kras-allelic-imbalance-strengths-and-weaknesses-in-numbers
#7
Gary J Doherty, Emma M Kerr, Carla P Martins
The identification of therapeutic vulnerabilities in mutant KRAS tumors has proven difficult to achieve. Burgess and colleagues recently reported in Cell that mutant/wild-type Kras allelic dosage determines clonal fitness and MEK inhibitor sensitivity in a leukemia model, demonstrating that KRAS allelic imbalance is likely an important and overlooked variable.
March 31, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28372921/microbial-tuning-of-the-mammalian-immune-system
#8
Eric G Pamer
Bacterial species constituting the intestinal microbiota are implicated in maintenance of health but also pathogenesis of inflammatory disease. The compositional complexity of the microbiota and metabolic interdependencies of microbial species challenge our ability to attribute host responses to specific bacterial strains. Studies using gnotobiotic mice, however, are providing important insights.
March 31, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28341301/disease-modeling-in-stem-cell-derived-3d-organoid-systems
#9
REVIEW
Devanjali Dutta, Inha Heo, Hans Clevers
Organoids are 3D in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture, functionality, and genetic signature of original tissues. Thus, organoid technology has been rapidly applied to understanding stem cell biology, organogenesis, and various human pathologies. The recent development of human patient-derived organoids has enabled disease modeling with precision, highlighting their great potential in biomedical applications, translational medicine, and personalized therapy...
March 21, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28330687/adipocyte-tumor-cell-metabolic-crosstalk-in-breast-cancer
#10
REVIEW
Andrew J Hoy, Seher Balaban, Darren N Saunders
The tumor stroma is a heterogeneous ecosystem comprising matrix, fibroblasts, and immune cells and has an important role in cancer progression. Adipocytes constitute a major component of breast stroma, and significant emerging evidence demonstrates a reciprocal metabolic adaptation between stromal adipocytes and breast cancer (BC) cells. Recent observations promote a model where adipocytes respond to cancer cell-derived endocrine and paracrine signaling to provide metabolic substrates, which in turn drive enhanced cancer cell proliferation, invasion, and treatment resistance...
March 19, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28325627/tlrs-go-linear-on-the-ubiquitin-edge
#11
REVIEW
Julia Zinngrebe, Henning Walczak
Toll-like receptors (TLRs) are crucial in protecting the host from pathogens. However, their exact role in disease remains incompletely understood. TLR signaling is tightly controlled because too little or too much TLR activation can result in immunodeficiency or autoinflammation, respectively. There is increasing evidence that linear ubiquitination, mediated by the linear ubiquitin chain assembly complex (LUBAC), plays a pivotal role in the regulation of TLR signaling. Recent advances have identified an intricate interaction between LUBAC and TLRs, with immunological consequences for infection and the development of autoinflammation in the host...
March 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28318994/more-flavor-for-flavonoid-based-interventions
#12
Nadeem O Kaakoush, Margaret J Morris
Poor diets are associated with obesity and a decline in cognitive function. Flavonoids are plant compounds that have been associated with improved metabolic parameters in obesity and reversal of cognitive decline. Given that microbial flavonoid conversion is important for bioactivity, flavonoid-derived neuroactive compounds may be functionally crucial in the gut microbiome-brain axis.
March 17, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28291707/epigenetics-of-atherosclerosis-emerging-mechanisms-and-methods
#13
REVIEW
Nadiya Khyzha, Azad Alizada, Michael D Wilson, Jason E Fish
Atherosclerosis is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls. Vessel occlusion, often occurring after plaque rupture, can result in myocardial and cerebral infarction. Epigenetic changes are increasingly being associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. Emerging genomic approaches that profile DNA methylation, chromatin accessibility, post-translational histone modifications, transcription factor binding, and RNA expression in low or single cell populations are poised to enhance our spatiotemporal understanding of atherogenesis...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28285807/a-brighter-side-to-thalidomide-its-potential-use-in-immunological-disorders
#14
REVIEW
David Millrine, Tadamitsu Kishimoto
Thalidomide and its derivatives are immunomodulatory drugs (IMiDs) known for their sedative, teratogenic, anti-angiogenic, and anti-inflammatory properties. Commonly used in the treatment of cancers such as multiple myeloma and myelodysplastic syndrome (MDS), IMiDs have also been used in the treatment of an inflammatory skin pathology associated with Hansen's disease/leprosy. They have also shown promise in the treatment of autoimmune disorders including systemic lupus erythmatosus (SLE) and inflammatory bowel disease (IBD)...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28285806/mitochondrial-sirtuins-and-molecular-mechanisms-of-aging
#15
REVIEW
Robert A H van de Ven, Daniel Santos, Marcia C Haigis
Advancing age is the major risk factor for the development of chronic diseases and is accompanied by changes in metabolic processes and mitochondrial dysfunction. Mitochondrial sirtuins (SIRT3-5) are part of the sirtuin family of NAD(+)-dependent deacylases and ADP-ribosyl transferases. The dependence on NAD(+) links sirtuin enzymatic activity to the metabolic state of the cell, poising them as stress sensors. Recent insights have revealed that SIRT3-5 orchestrate stress responses through coordinated regulation of substrate clusters rather than of a few key metabolic enzymes...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28283249/sphingosine-1-phosphate-signaling-in-inflammatory-bowel-disease
#16
REVIEW
Ole Haagen Nielsen, Yuan Li, Bengt Johansson-Lindbom, Mehmet Coskun
An unmet medical need exists for the development of targeted therapies for the treatment of inflammatory bowel disease (IBD) with easily administered and stable oral drugs, particularly as most patients on biologics [i.e., tumor necrosis factor (TNF) inhibitors and anti-integrins] are either primary non-responders or lose responsiveness during maintenance treatment. A new class of small molecules, sphingosine-1-phosphate (S1P) receptor modulators, has recently shown efficacy in IBD. Here we provide an overview of the mechanism of action of this novel treatment principle in the context of intestinal inflammation...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28279624/p21-a-two-faced-genome-guardian
#17
REVIEW
Alexandros G Georgakilas, Olga A Martin, William M Bonner
Upon DNA damage or other stressors, the tumor suppressor p53 is activated, leading to transient expression of the cyclin-dependent kinase inhibitor (CKI) p21. This either triggers momentary G1 cell cycle arrest or leads to a chronic state of senescence or apoptosis, a form of genome guardianship. In the clinic, the presence of p21 has been considered an indicator of wildtype p53 activity. However, recent evidence suggests that p21 also acts as an oncogenic factor in a p53-deficient environment. Here, we discuss the controversial aspects of the two-faced involvement of p21 in cancer and speculate on how this new information may increase our understanding of its role in cancer pathogenesis...
April 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28196625/-did-he-who-made-the-lamb-make-thee-new-developments-in-treating-the-fearful-symmetry-of-acute-myeloid-leukemia
#18
REVIEW
Gabriela Brumatti, Najoua Lalaoui, Andrew H Wei, John Silke
Malignant cells must circumvent endogenous cell death pathways to survive and develop into cancers. Acquired cell death resistance also sets up malignant cells to survive anticancer therapies. Acute Myeloid Leukemia (AML) is an aggressive blood cancer characterized by high relapse rate and resistance to cytotoxic therapies. Recent collaborative profiling projects have led to a greater understanding of the 'fearful symmetry' of the genomic landscape of AML, and point to the development of novel potential therapies that can overcome factors linked to chemoresistance...
March 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28188103/kidney-organoids-a-translational-journey
#19
REVIEW
Ryuji Morizane, Joseph V Bonventre
Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3D organ-buds termed 'organoids' from hPSCs; these consist of a variety of cell types in vitro that mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro, especially when combined with CRISPR/Cas9-based genome-editing...
March 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28188102/mitochondrial-dynamics-coupling-mitochondrial-fitness-with-healthy-aging
#20
REVIEW
David Sebastián, Manuel Palacín, Antonio Zorzano
Aging is associated with a decline in mitochondrial function and the accumulation of abnormal mitochondria. However, the precise mechanisms by which aging promotes these mitochondrial alterations and the role of the latter in aging are still not fully understood. Mitochondrial dynamics is a key process regulating mitochondrial function and quality. Altered expression of some mitochondrial dynamics proteins has been recently associated with aging and with age-related alterations in yeast, Caenorhabditis elegans, mice, and humans...
March 2017: Trends in Molecular Medicine
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