scholarly journals Translational Stroke Research Review: Using the Mouse to Model Human Futile Recanalization and Reperfusion Injury in Ischemic Brain Tissue

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3308
Author(s):  
Emilia Conti ◽  
Benedetta Piccardi ◽  
Alessandro Sodero ◽  
Laura Tudisco ◽  
Ivano Lombardo ◽  
...  
Keyword(s):  
Mouse Models ◽  
Research Review ◽  
Preclinical Research ◽  
Dynamic Changes ◽  
Clinical Prognosis ◽  
Ischemic Brain ◽  
Stroke Research ◽  
Flow Restoration ◽  
Ischemic Brain Tissue ◽  
Poor Clinical Prognosis

The approach to reperfusion therapies in stroke patients is rapidly evolving, but there is still no explanation why a substantial proportion of patients have a poor clinical prognosis despite successful flow restoration. This issue of futile recanalization is explained here by three clinical cases, which, despite complete recanalization, have very different outcomes. Preclinical research is particularly suited to characterize the highly dynamic changes in acute ischemic stroke and identify potential treatment targets useful for clinical translation. This review surveys the efforts taken so far to achieve mouse models capable of investigating the neurovascular underpinnings of futile recanalization. We highlight the translational potential of targeting tissue reperfusion in fully recanalized mouse models and of investigating the underlying pathophysiological mechanisms from subcellular to tissue scale. We suggest that stroke preclinical research should increasingly drive forward a continuous and circular dialogue with clinical research. When the preclinical and the clinical stroke research are consistent, translational success will follow.

scholarly journals SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jing Li ◽  
Ruiqin Wu ◽  
Mingo M. H. Yung ◽  
Jing Sun ◽  
Zhuqing Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Kinase Activity ◽  
Regulatory Mechanism ◽  
Platinum Resistance ◽  
Platinum Drug ◽  
Clinical Prognosis ◽  
Platinum Resistant ◽  
Poor Clinical Prognosis ◽  
Stat Pathway

AbstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.

scholarly journals CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sibel Durlanik ◽  
Katrin Fundel-Clemens ◽  
Coralie Viollet ◽  
Heinrich J. Huber ◽  
Martin Lenter ◽  
...  
Keyword(s):  
Clinical Prognosis ◽  
Rigorous Evaluation ◽  
Macrophage Recruitment ◽  
Upstream Regulator ◽  
Lack Of Information ◽  
Important Player ◽  
Inhibitory Signaling ◽  
Support Tumor Growth ◽  
Poor Clinical Prognosis ◽  
Pai 1

AbstractMore than 70% of colorectal, prostate, ovarian, pancreatic and breast cancer specimens show expression of CD276 (B7–H3), a potential immune checkpoint family member. Several studies have shown that high CD276 expression in cancer cells correlates with a poor clinical prognosis. This has been associated with the presence of lower tumor infiltrating leukocytes. Among those, tumor-associated macrophages can comprise up to 50% of the tumor mass and are thought to support tumor growth through various mechanisms. However, a lack of information on CD276 function and interaction partner(s) impedes rigorous evaluation of CD276 as a therapeutic target in oncology. Therefore, we aimed to understand the relevance of CD276 in tumor-macrophage interaction by employing a 3D spheroid coculture system with human cells. Our data show a role for tumor-expressed CD276 on the macrophage recruitment into the tumor spheroid, and also in regulation of the extracellular matrix modulator PAI-1. Furthermore, our experiments focusing on macrophage-expressed CD276 suggest that the antibody-dependent CD276 engagement triggers predominantly inhibitory signaling networks in human macrophages.

scholarly journals Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sebastian R. Nielsen ◽  
Jan E. Strøbech ◽  
Edward R. Horton ◽  
Rene Jackstadt ◽  
Anu Laitala ◽  
...  
Keyword(s):  
Cd8 T Cells ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Ductal Adenocarcinoma ◽  
Cancer Growth ◽  
Cancer Therapies ◽  
Cell Type ◽  
Clinical Prognosis ◽  
Tumor Associated Neutrophils ◽  
Poor Clinical Prognosis

AbstractPancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.

Post-ischemic brain tissue alkalosis suppressed by U74006F

1993 ◽  
Vol 114 (1) ◽  
pp. 36-39 ◽  
Author(s):  
Ana M.Q.Vande Linde ◽  
Michael Chopp ◽  
Sue Ann Lee ◽  
Lonni R. Schultz ◽  
K.M.A. Welch
Keyword(s):  
Brain Tissue ◽  
Ischemic Brain ◽  
Ischemic Brain Tissue

FOXM1 is required for small cell lung cancer tumorigenesis and associated with poor clinical prognosis

Oncogene ◽  
2021 ◽  
Author(s):  
Sheng-Kai Liang ◽  
Chia-Chan Hsu ◽  
Hsiang-Lin Song ◽  
Yu-Chi Huang ◽  
Chun-Wei Kuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Prognosis ◽  
Poor Clinical Prognosis

Mouse models for translational preclinical research in immuno-oncology

2016 ◽  
Vol 69 ◽  
pp. S53-S54
Author(s):  
A. Wulf-Goldenberg ◽  
M. Stecklum ◽  
Z. Reiner ◽  
I. Fichtner ◽  
J. Hoffmann
Keyword(s):  
Mouse Models ◽  
Preclinical Research

scholarly journals Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

2010 ◽  
Vol 30 (4) ◽  
pp. 703-717 ◽  
Author(s):  
Tracy D Farr ◽  
Susanne Wegener
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Complete Recovery ◽  
Research Translation ◽  
Resonance Imaging ◽  
Preclinical Research ◽  
Stroke Research ◽  
Future Potential ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual

Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction.

scholarly journals 356 Polypoid melanoma is associated with aggressive histopathological characteristics and poor clinical prognosis

2021 ◽  
Vol 141 (5) ◽  
pp. S62
Author(s):  
E. Pedersen ◽  
P. Harms ◽  
L. Zhao ◽  
A. Andea ◽  
M. Chan ◽  
...  
Keyword(s):  
Clinical Prognosis ◽  
Poor Clinical Prognosis

Downregulated SASH1 expression indicates poor clinical prognosis in gastric cancer

2018 ◽  
Vol 74 ◽  
pp. 83-91 ◽  
Author(s):  
Nan Zhou ◽  
Can Liu ◽  
Xudong Wang ◽  
Qinsheng Mao ◽  
Qin Jin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Prognosis ◽  
Poor Clinical Prognosis

scholarly journals Advances in Diagnostic Imaging of Hepatopulmonary Syndrome

2022 ◽  
Vol 8 ◽  
Author(s):  
Bi-Wei Luo ◽  
Zhi-Yong Du
Keyword(s):  
Liver Disease ◽  
Pulmonary Complication ◽  
Hepatopulmonary Syndrome ◽  
Pulmonary Angiography ◽  
Pulmonary Perfusion ◽  
Clinical Prognosis ◽  
Vascular Dilatation ◽  
Progressive Liver Disease ◽  
Poor Clinical Prognosis ◽  
Timely Treatment

Hepatopulmonary syndrome (HPS) is a serious pulmonary complication of progressive liver disease that leads to a poor clinical prognosis. Patients with HPS may develop acute respiratory failure, which requires intensive care and therapy. At present, the only effective treatment is liver transplantation; therefore, early diagnosis and timely treatment are of considerable significance. The three main features of HPS are liver disease, oxygenation disorder, and intrapulmonary vascular dilatation (IPVD). Diagnosing HPS is challenging due to the difficulty in detecting the presence or absence of IPVD. As such, imaging examination is very important for detecting IPVD. This paper reviews the imaging methods for diagnosing HPS such as ultrasound, dynamic pulmonary perfusion imaging, pulmonary angiography, and computed tomography.

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