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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/28623084/pathogenesis-of-human-systemic-lupus-erythematosus-a-cellular-perspective
#1
REVIEW
Vaishali R Moulton, Abel Suarez-Fueyo, Esra Meidan, Hao Li, Masayuki Mizui, George C Tsokos
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors...
June 13, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28587830/early-detection-of-cancer-in-blood-using-single-cell-analysis-a-proposal
#2
REVIEW
Alexander Krasnitz, Jude Kendall, Joan Alexander, Dan Levy, Michael Wigler
Here, we explore the potential of single-cell genomic analysis in blood for early detection of cancer; we consider a method that screens the presence of recurrent patterns of copy number (CN) alterations using sparse single-cell sequencing. We argue for feasibility, based on in silico analysis of existing single-cell data and cancer CN profiles. Sampling procedures from existing diploid single cells can render data for a cell with any given profile. Sampling from multiple published tumor profiles can interrogate cancer clonality via an algorithm that tests the multiplicity of close pairwise similarities among single-cell cancer genomes...
June 3, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28583420/the-boosting-potential-of-bacteria-in-cancer-immunotherapy
#3
David C Binder, Derek A Wainwright
Salmonella Typhimurium, engineered to express flagellin B, recently demonstrated unprecedented tumor control through a TLR-dependent mechanism. Here, we review new observations that support the potential of utilizing modified bacteria to enhance antitumor immunity. We also discuss the implications of these findings for clinical applications, including immune checkpoint blockade therapies.
June 2, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28576602/biomarkers-of-human-pluripotent-stem-cell-derived-cardiac-lineages
#4
REVIEW
Rhys J P Skelton, Timothy J Kamp, David A Elliott, Reza Ardehali
Human pluripotent stem cells (hPSCs) offer a practical source for the de novo generation of cardiac tissues and a unique opportunity to investigate cardiovascular lineage commitment. Numerous strategies have focused on the in vitro production of cardiomyocytes, smooth muscle, and endothelium from hPSCs. However, these differentiation protocols often yield undesired cell types. Thus, establishing a set of stage-specific markers for pure cardiac subpopulations will assist in defining the hierarchy of cardiac differentiation, aid in the development of cellular therapy, and facilitate drug screening and disease modeling...
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28576601/linc-ing-the-noncoding-genome-to-heart-function-beating-hypertrophy
#5
Shambhabi Chatterjee, Christian Bär, Thomas Thum
The principal event of aberrant gene expression occurs in numerous disorders and syndromes, including heart failure. LncRNAs may constitute powerful treatment targets because they intensively interact with their genetic environment, as they are important regulators of genetic networks. Recent advances on the functional roles of lncRNAs in cardiac hypertrophy are expected to usher improved therapeutic strategies.
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28571832/de-novo-gene-expression-reconstruction-in-space
#6
REVIEW
Je H Lee
The biological function of a gene often depends on spatial context, and an atlas of transcriptional regulation could be instrumental in defining functional elements across the genome. Despite recent advances in single-cell RNA sequencing and in situ RNA imaging, fundamental barriers limit the speed, genome-wide coverage, and resolution of de novo transcriptome assembly in space. Here, I discuss potential next-generation approaches for the de novo assembly of the transcriptome in space, and propose more efficient methods of detecting long-range spatial variations in gene expression...
May 29, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28501348/single-cell-rna-sequencing-unraveling-the-brain-one-cell-at-a-time
#7
REVIEW
Dimitry Ofengeim, Nikolaos Giagtzoglou, Dann Huh, Chengyu Zou, Junying Yuan
Single-cell RNA sequencing (scRNA-seq) is an exciting new technology allowing the analysis of transcriptomes from individual cells, and is ideally suited to address the inherent complexity and dynamics of the central nervous system. scRNA-seq has already been applied to the study of molecular taxonomy of the brain. These works have paved the way to expanding our understanding of the nervous system and provide insights into cellular susceptibilities and molecular mechanisms in neurological and neurodegenerative diseases...
May 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28499701/should-we-stop-saying-glia-and-neuroinflammation
#8
REVIEW
Roser Masgrau, Carmen Guaza, Richard M Ransohoff, Elena Galea
Central nervous system (CNS) therapeutics based on the theoretical framework of neuroinflammation have only barely succeeded. We argue that a problem may be the wrong use of the term 'neuroinflammation' as a distinct nosological entity when, based on recent evidence, it may not explain CNS disease pathology. Indeed, the terms 'neuroinflammation' and 'glia' could be obsolete. First, unbiased molecular profiling of CNS cell populations and individual cells reveals striking phenotypic heterogeneity in health and disease...
May 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28478951/a-crispr-approach-to-neurodegenerative-diseases
#9
Martin Kampmann
A major barrier to developing effective therapies for neurodegenerative diseases is our incomplete understanding of the underlying cellular mechanisms. Genetic screens in human-induced pluripotent stem cell-derived neurons can elucidate such mechanisms. Genome-wide screens using CRISPR interference and CRISPR activation provide complementary biological insights and may reveal potential therapeutic targets.
May 4, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28478950/emerging-role-for-methylation-in-multiple-sclerosis-beyond-dna
#10
REVIEW
Lindsay M Webb, Mireia Guerau-de-Arellano
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance...
May 4, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28461154/pathophysiology-of-tfii-i-old-guard-wearing-new-hats
#11
REVIEW
Ananda L Roy
The biochemical properties of the signal-induced multifunctional transcription factor II-I (TFII-I) indicate that it is involved in a variety of gene regulatory processes. Although gene ablation in murine models and cell-based assays show that it is encoded by an essential gene, GTF2I/Gtf2i, its physiologic role in human disorders was relatively unknown until recently. Novel studies show that it is involved in an array of human diseases including neurocognitive disorders, systemic lupus erythematosus (SLE), and cancer...
April 28, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28442216/trem2-microglia-and-neurodegenerative-diseases
#12
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/28408271/quid-pro-quo-a-tumor-is-not-alone
#13
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/28396056/connecting-the-metabolic-and-immune-responses-to-cancer
#14
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
#15
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/28483344/the-exceptional-vulnerability-of-humans-to-alzheimer-s-disease
#16
REVIEW
Lary C Walker, Mathias Jucker
Like many humans, non-human primates deposit copious misfolded Aβ protein in the brain as they age. Nevertheless, the complete behavioral and pathologic phenotype of Alzheimer's disease, including Aβ plaques, neurofibrillary (tau) tangles, and dementia, has not yet been identified in a non-human species. Recent research suggests that the crucial link between Aβ aggregation and tauopathy is somehow disengaged in aged monkeys. Understanding why Alzheimer's disease fails to develop in species that are biologically proximal to humans could disclose new therapeutic targets in the chain of events leading to neurodegeneration and dementia...
June 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28427863/ros-in-cancer-the-burning-question
#17
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...
May 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28416139/cars-synthetic-immunoreceptors-for-cancer-therapy-and-beyond
#18
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...
May 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28400243/cancer-manipulation-of-host-physiology-lessons-from-pancreatic-cancer
#19
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...
May 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28372921/microbial-tuning-of-the-mammalian-immune-system
#20
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.
May 2017: Trends in Molecular Medicine
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