Go to JCI Insight
Jci spelled out white on transparent.20160208
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Cellular senescence in human disease (Apr 2018)
    • Fibrosis (Jan 2018)
    • Glia and Neurodegeneration (Sep 2017)
    • Transplantation (Jun 2017)
    • Nuclear Receptors (Apr 2017)
    • Metabolism and Inflammation (Jan 2017)
    • Hypoxia and Inflammation (Oct 2016)
    • View all review series...
  • Collections
    • Recently published
    • Commentaries
    • Concise Communication
    • Editorials
    • Opinion
    • Scientific Show Stoppers
    • Top read articles
    • In-Press Preview
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

Jci only white

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication

Commentary

  • 1,272 Articles
  • 0 Posts
  • ←
  • 1
  • 2
  • 3
  • …
  • 127
  • 128
  • →
The evolving landscape of predictive biomarkers of response to PARP inhibitors
Anish Thomas, … , Junko Murai, Yves Pommier
Anish Thomas, … , Junko Murai, Yves Pommier
Published April 16, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120388.
View: Text | PDF

The evolving landscape of predictive biomarkers of response to PARP inhibitors

  • Text
  • PDF
Abstract

Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis — olaparib, niraparib, and rucaparib — were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response. In this issue of the JCI, Makvandi and coworkers describe an approach to address this question using [18F]FluorThanatrace, an [18F]-labeled PARP-1 inhibitor, for PET. The tracer was taken up by patient tumor tissue and appeared to differentiate levels of PARP-1 expression; however, future studies should be aimed at determining if this tracer can be used to stratify patient response to PARPi therapy.

Authors

Anish Thomas, Junko Murai, Yves Pommier

×

A new concept of fibroblast dynamics in post–myocardial infarction remodeling
Thomas Eschenhagen
Thomas Eschenhagen
Published April 16, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI121079.
View: Text | PDF

A new concept of fibroblast dynamics in post–myocardial infarction remodeling

  • Text
  • PDF
Abstract

The identity and function of the fibroblast, a highly prevalent cell type in the heart, have remained poorly defined. Recent faithful genetic lineage–tracing studies revealed that during development, the cardiac fibroblasts are derived from the epicardium and the endothelium, whereas in the adult heart, they constitute the cardiac injury–responsive resident fibroblast. In the current issue of the JCI, Molkentin and colleagues decipher the time course and mechanism of the fibroblast in response to myocardial infarction (MI). The model they propose is surprisingly simple and clear. It consists of three major phases. First, fibroblasts in the ischemic area die. Second, surrounding fibroblasts proliferate and migrate into the spaces created by dying cardiomyocytes over a few days. The new fibroblasts in the scar are activated and adopt a smooth muscle actin– and periostin-positive “myofibroblast” phenotype, which appears to last as long as the scar is not mature (~10 days after MI). In the third phase, initially proliferating myofibroblasts lose smooth muscle actin expression and convert to a nonproliferating, matrix-producing phenotype with a newly acquired tendon gene signature. Interestingly, this state appears to differ from that of quiescent fibroblasts in the uninjured heart, as it is resistant to proliferative stimuli. These cells are therefore termed “matrifibrocytes,” a novel category whose study will certainly further advance the field.

Authors

Thomas Eschenhagen

×

Classical IL-6 signaling: a promising therapeutic target for pulmonary arterial hypertension
Soni Savai Pullamsetti, … , Werner Seeger, Rajkumar Savai
Soni Savai Pullamsetti, … , Werner Seeger, Rajkumar Savai
Published April 9, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120415.
View: Text | PDF

Classical IL-6 signaling: a promising therapeutic target for pulmonary arterial hypertension

  • Text
  • PDF
Abstract

Current therapies for pulmonary arterial hypertension (PAH) provide symptomatic relief and improve prognosis but fall short of improving long-term survival. There is emerging evidence for a role of inflammatory mediators, primarily IL-6, in the pathogenesis of PAH. However, the mechanisms by which IL-6 potentially affects PAH are unknown. In this issue of the JCI, Tamura, Phan, and colleagues identified ectopic upregulation of the membrane-bound IL-6 receptor (IL6R), indicating classical IL-6 signaling in the smooth muscle layer of remodeled vessels in human and experimental PAH. They performed a series of in vitro and in vivo experiments that provide deeper insights into the mechanisms of classical IL-6 signaling and propose interventions directed against IL6R as a potential therapeutic strategy for PAH.

Authors

Soni Savai Pullamsetti, Werner Seeger, Rajkumar Savai

×

Blocking immune intrusion into the brain suppresses epilepsy in Rasmussen’s encephalitis model
Lawrence Steinman
Lawrence Steinman
Published April 9, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120444.
View: Text | PDF

Blocking immune intrusion into the brain suppresses epilepsy in Rasmussen’s encephalitis model

  • Text
  • PDF
Abstract

Rasmussen’s encephalitis (RE) is a neuroinflammatory disease that typically affects only one hemisphere of the brain, resulting in severe seizures. Sixty years after the disease was first described, the preferred and best treatment option for RE is grotesque and involves removing a hemisphere of the brain (hemispherectomy); therefore, a better understanding of this seizure disorder may provide additional, less invasive therapeutic options. In this issue of the JCI, Carmant and colleagues have developed an animal model of this focal seizure disorder. The model provides experimental insights into the pathogenesis of RE and potential new treatments for this disease.

Authors

Lawrence Steinman

×

Targeting the accomplice to thwart the culprit: a new target for the prevention of amyloid deposition
David R. Borchelt
David R. Borchelt
Published March 30, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120414.
View: Text | PDF

Targeting the accomplice to thwart the culprit: a new target for the prevention of amyloid deposition

  • Text
  • PDF
Abstract

Inheritance of the E4 allele of the apolipoprotein E gene (APOE4) substantially increases the risk of developing late-onset Alzheimer disease (AD). A large body of evidence has firmly established a role for apoE in modulating the risk of developing the amyloid plaque pathology that is pathognomonic for AD. In this issue of the JCI, Liao and colleagues discovered that antibodies against a nonlipidated form of apoE4 are highly effective in delaying the deposition of amyloid β (Aβ) peptides in mouse models of AD pathology. Using a combination of passive immunization and viral-mediated expression of recombinant antibodies, the authors show that Fc receptor–mediated clearance of the nonlipidated apoE4 was critical in delaying Aβ deposition. Collectively, this study identifies a new therapeutic target that could be exploited to prevent, or possibly reverse, the Aβ pathology of AD.

Authors

David R. Borchelt

×

What goes around comes around: modeling malaria transmission from humans back to mosquitos
Kazutoyo Miura, Peter D. Crompton
Kazutoyo Miura, Peter D. Crompton
Published March 12, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120260.
View: Text | PDF

What goes around comes around: modeling malaria transmission from humans back to mosquitos

  • Text
  • PDF
Abstract

Malaria, caused by mosquito-transmitted Plasmodium parasites, continues to take a major toll on global health. The development of drugs and vaccines that reduce malaria transmission from humans back to mosquitos could contribute to the control and eventual eradication of malaria, but research models for the early clinical evaluation of candidate interventions are lacking. In this issue of the JCI, Collins and colleagues report the successful transmission of Plasmodium falciparum parasites from humans to mosquitoes during controlled human malaria infection, thus providing a potential tool to accelerate the development of much needed transmission-blocking drugs and vaccines.

Authors

Kazutoyo Miura, Peter D. Crompton

×

Cell-based molecularly targeted therapy: targeting oncoproteins with T cell receptor gene therapy
Christian S. Hinrichs
Christian S. Hinrichs
Published March 12, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120386.
View: Text | PDF

Cell-based molecularly targeted therapy: targeting oncoproteins with T cell receptor gene therapy

  • Text
  • PDF
Abstract

As oncogenes drive carcinogenesis and promote cancer cell survival, they are highly attractive therapeutic targets, and oncogene-targeting small molecules have achieved some clinical success. While many oncogenes are presently considered to be “druggable,” tumors often acquire treatment resistance, and patients are rarely cured in response to oncogene-specific treatment. In this issue of the JCI, Veatch and colleagues describe a patient with metastatic acral melanoma who experienced a complete tumor response following infusion of tumor-infiltrating T cells that targeted multiple tumor antigens, including a BRAFV600E driver mutation. T cells genetically engineered to express an anti-BRAFV600E T cell receptor (TCR) from the patient demonstrated recognition of an epitope that spanned the BRAFV600E mutation. These findings suggest that BRAFV600E might be targeted therapeutically with adoptive transfer of anti-BRAFV600E T cells. This research supports the emerging therapeutic paradigm of targeting oncogenic drivers with T cell immunotherapy.

Authors

Christian S. Hinrichs

×

Unleashing the therapeutic potential of oncolytic viruses
Praveen K. Bommareddy, Howard L. Kaufman
Praveen K. Bommareddy, Howard L. Kaufman
Published March 5, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120303.
View: Text | PDF

Unleashing the therapeutic potential of oncolytic viruses

  • Text
  • PDF
Abstract

Oncolytic viruses (OVs) are a versatile new class of therapeutic agents based on native or genetically modified viruses that selectively replicate in tumor cells and can express therapeutic transgenes designed to target cells within the tumor microenvironment and/or host immunity. To date, however, confirmation of the underlying mechanism of action and an understanding of innate and acquired drug resistance for most OVs have been limited. In this issue of the JCI, Zamarin et al. report a comprehensive analysis of an oncolytic Newcastle disease virus (NDV) using both murine melanoma tumor models and human tumor explants to explore how the virus promotes tumor eradication and details of the mechanisms involved. These findings have implications for the optimization of oncolytic immunotherapy, at least that based on NDV, and further confirm that specific combinatorial approaches are promising for clinical development.

Authors

Praveen K. Bommareddy, Howard L. Kaufman

×

Opening windows for bone remodeling through a SLIT
Jameel Iqbal, … , Se-Min Kim, Mone Zaidi
Jameel Iqbal, … , Se-Min Kim, Mone Zaidi
Published March 5, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120325.
View: Text | PDF

Opening windows for bone remodeling through a SLIT

  • Text
  • PDF
Abstract

Bone formation and resorption are tightly coupled, and dysfunction of either process leads to bone diseases, such as osteoporosis. Bone-forming agents have been explored clinically to increase bone density; however, long-term efficacy of these strategies is limited due to the accompanying increase in resorption in response to increased bone formation. Axonal guidance molecules have recently been shown to regulate formation-resorption coupling and thus have the potential for osteoporosis therapy. In this issue of the JCI, Kim et al. demonstrate that osteoclast-secreted SLIT3 influences bone formation and resorption by promoting osteoblast migration and suppressing osteoclast differentiation. Activation of SLIT3/ROBO signaling in ovariectomized mice increased bone mass, suggesting that SLIT3 should be further explored as a therapeutic target.

Authors

Jameel Iqbal, Tony Yuen, Se-Min Kim, Mone Zaidi

×

Alternative macrophages in atherosclerosis: not always protective!
Benoit Pourcet, Bart Staels
Benoit Pourcet, Bart Staels
Published February 19, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120123.
View: Text | PDF

Alternative macrophages in atherosclerosis: not always protective!

  • Text
  • PDF
Abstract

Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163+ macrophages, which previously were thought to be beneficial.

Authors

Benoit Pourcet, Bart Staels

×
  • ←
  • 1
  • 2
  • 3
  • …
  • 127
  • 128
  • →

No posts were found with this tag.

Advertisement
Follow JCI: Facebook logo white Twitter logo v2 Rss icon
Copyright © 2018 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts