Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
477
result(s) for
"Cohen, Ivan"
Sort by:
Green lantern : the animated series
When Hal Jordan and his Green Lantern partner Kilowog locate a Green Lantern ring abandoned in space, they investigate to see if one of their comrades has fallen, or if something more sinister is happening.
Book
LDH-A regulates the tumor microenvironment via HIF-signaling and modulates the immune response
Previous studies show that LDH-A knockdown reduces orthotopic 4T1 breast tumor lactate and delays tumor growth and the development of metastases in nude mice. Here, we report significant changes in the tumor microenvironment (TME) and a more robust anti-tumor response in immune competent BALB/c mice. 4T1 murine breast cancer cells were transfected with shRNA plasmids directed against LDH-A (KD) or a scrambled control plasmid (NC). Cells were also transduced with dual luciferase-based reporter systems to monitor HIF-1 activity and the development of metastases by bioluminescence imaging, using HRE-sensitive and constitutive promoters, respectively. The growth and metastatic profile of orthotopic 4T1 tumors developed from these cell lines were compared and a primary tumor resection model was studied to simulate the clinical management of breast cancer. Primary tumor growth, metastasis formation and TME phenotype were significantly different in LDH-A KD tumors compared with controls. In LDH-A KD cells, HIF-1 activity, hexokinase 1 and 2 expression and VEGF secretion were reduced. Differences in the TME included lower HIF-1α expression that correlated with lower vascularity and pimonidazole staining, higher infiltration of CD3+ and CD4+ T cells and less infiltration of TAMs. These changes resulted in a greater delay in metastases formation and 40% long-term survivors (>20 weeks) in the LDH-A KD cohort following surgical resection of the primary tumor. We show for the first time that LDH-depletion inhibits the formation of metastases and prolongs survival of mice through changes in tumor microenvironment that modulate the immune response. We attribute these effects to diminished HIF-1 activity, vascularization, necrosis formation and immune suppression in immune competent animals. Gene-expression analyses from four human breast cancer datasets are consistent with these results, and further demonstrate the link between glycolysis and immune suppression in breast cancer.
Journal Article
Law and disorder
It is an uneasy time in Gotham, and some new executive at Simon Stagg's warehouse seems to be behind the trouble--but Batman and Katana are on the case.
Book
CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours
Limiting metabolic competition in the tumour microenvironment may increase the effectiveness of immunotherapy. Owing to its crucial role in the glucose metabolism of activated T cells, CD28 signalling has been proposed as a metabolic biosensor of T cells
1
. By contrast, the engagement of CTLA-4 has been shown to downregulate T cell glycolysis
1
. Here we investigate the effect of CTLA-4 blockade on the metabolic fitness of intra-tumour T cells in relation to the glycolytic capacity of tumour cells. We found that CTLA-4 blockade promotes metabolic fitness and the infiltration of immune cells, especially in glycolysis-low tumours. Accordingly, treatment with anti-CTLA-4 antibodies improved the therapeutic outcomes of mice bearing glycolysis-defective tumours. Notably, tumour-specific CD8
+
T cell responses correlated with phenotypic and functional destabilization of tumour-infiltrating regulatory T (T
reg
) cells towards IFNγ- and TNF-producing cells in glycolysis-defective tumours. By mimicking the highly and poorly glycolytic tumour microenvironments in vitro, we show that the effect of CTLA-4 blockade on the destabilization of T
reg
cells is dependent on T
reg
cell glycolysis and CD28 signalling. These findings indicate that decreasing tumour competition for glucose may facilitate the therapeutic activity of CTLA-4 blockade, thus supporting its combination with inhibitors of tumour glycolysis. Moreover, these results reveal a mechanism by which anti-CTLA-4 treatment interferes with T
reg
cell function in the presence of glucose.
CTLA-4 promotes glucose uptake by tumour-infiltrating regulatory T cells, making them unstable.
Journal Article
The son of the Man-Bat
Batman has a cure for Kirk Langstom, the Man-Bat, but suddenly a second man-sized bat appears in Gotham City--a junior high school student named Tim Quan.
Book
Local hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep
Rapid eye movement sleep (REMS) is a peculiar brain state combining the behavioral components of sleep and the electrophysiological profiles of wake. After decades of research our understanding of REMS still is precluded by the difficulty to observe its spontaneous dynamics and the lack of multimodal recording approaches to build comprehensive datasets. We used functional ultrasound (fUS) imaging concurrently with extracellular recordings of local field potentials (LFP) to reveal brain-wide spatiotemporal hemodynamics of single REMS episodes. We demonstrate for the first time the close association between global hyperemic events – largely outmatching wake levels in most brain regions – and local hippocampal theta (6–10 Hz) and fast gamma (80–110 Hz) events in the CA1 region. In particular, the power of fast gamma oscillations strongly correlated with the amplitude of subsequent vascular events. Our findings challenge our current understanding of neurovascular coupling and question the evolutionary benefit of such energy-demanding patterns in REMS function.
Neural activity during REM sleep is similar to the waking state. Here, the authors measure blood volume with neurofunctional ultrasound imaging together with hippocampal neural activity during REM sleep and report that fast gamma oscillations are coupled to a brain-wide upregulation of vascular flow.
Journal Article
Star Wars : the prequel trilogy stories
Collects eighteen stories from the Star Wars prequel trilogy films.
Book
Adaptive modulation of brain hemodynamics across stereotyped running episodes
During locomotion, theta and gamma rhythms are essential to ensure timely communication between brain structures. However, their metabolic cost and contribution to neuroimaging signals remain elusive. To finely characterize neurovascular interactions during locomotion, we simultaneously recorded mesoscale brain hemodynamics using functional ultrasound (fUS) and local field potentials (LFP) in numerous brain structures of freely-running overtrained rats. Locomotion events were reliably followed by a surge in blood flow in a sequence involving the retrosplenial cortex, dorsal thalamus, dentate gyrus and CA regions successively, with delays ranging from 0.8 to 1.6 seconds after peak speed. Conversely, primary motor cortex was suppressed and subsequently recruited during reward uptake. Surprisingly, brain hemodynamics were strongly modulated across trials within the same recording session; cortical blood flow sharply decreased after 10–20 runs, while hippocampal responses strongly and linearly increased, particularly in the CA regions. This effect occurred while running speed and theta activity remained constant and was accompanied by an increase in the power of hippocampal, but not cortical, high-frequency oscillations (100–150 Hz). Our findings reveal distinct vascular subnetworks modulated across fast and slow timescales and suggest strong hemodynamic adaptation, despite the repetition of a stereotyped behavior.
Theta and gamma rhythms are essential to ensure timely communication between brain structures during locomotion. Here the authors investigate the association between cerebral blood flow and neural oscillations in freely behaving mice running a linear track.
Journal Article
Teen Titans go! Vol. 5, Falling stars
\"Being a superhero is tough enough, but the team must face some everyday chores and obstacles that may prove to be too much, even for them. The Titans tackle the single most terrifying word in the English language: 'dentist.' Will Robin's dental routine save him from making a dreaded trip? Then, the heroes get crafty when Raven and Cyborg create a pair of spooky-looking leggings from a pattern in one of Raven's arcane books\"-- Provided by publisher.
BOOK
Impact of the Tumor Microenvironment on Tumor-Infiltrating Lymphocytes: Focus on Breast Cancer
Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration–approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors. We also review recent clinical trials of immunotherapy in breast cancer and provide a number of interesting questions that will need to be answered for successful breast cancer immunotherapy.
Journal Article