advanced-animal-model-colorectal-metastasis-liver-imaging-techniques

Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

Patients with a limited number of hepatic metastases and slow rates of progression can be successfully treated with local treatment approaches1,2. ...

The University of Chicago

To study the mechanisms of action of the antioxidants, n-acetylcysteine (NAC), and the nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase oxidase inhibitor, apocynin, on intravitreous neovascularization (IVNV), and retinal avascularity in a rat model of retinopathy of prematurity (ROP).

Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity.

To study NAD(P)H oxidase-dependent outcomes after oxygen stresses that are similar to those experienced by preterm infants today using a rat model of retinopathy of prematurity.

Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model.

Images of second harmonic generation (SHG) in needle-shaped ZnO rods obtained from individual structures show areas of enhanced second harmonic intensity along the longitudinal axis of the rod that are periodically distributed and symmetrically situated relative to the rod midpoint. The spatial modulation is a direct consequence of the fundamental optical field coupling into standing wave resonator modes of the ZnO structure, leading to an enhanced backscattered second harmonic condition that cannot be achieved in bulk ZnO. A more complicated second harmonic image is observed when excitation is below the band gap, which is attributed to whispering gallery modes. This physical phenomenon, which extends beyond just ZnO to many other optical materials, could pave the way to new applications that exploit the nonlinear optical properties of individual structures.

Direct imaging of optical cavity modes in ZnO rods using second harmonic generation microscopy.

To evaluate associations between conditions of maternal new-onset gestational hypertension (mHTN) and the features imparting risk of severe retinopathy of prematurity (ROP) in preterm infants.

New-onset maternal gestational hypertension and risk of retinopathy of prematurity.

Metastatic tumors are a major source of morbidity and mortality for most cancers. Interaction of circulating tumor cells with endothelium, platelets and neutrophils play an important role in the early stages of metastasis formation. These complex dynamics have proven difficult to study in experimental models. Prior computational models of metastases have focused on tumor cell growth in a host environment, or prediction of metastasis formation from clinical data. We used agent-based modeling (ABM) to dynamically represent hypotheses of essential steps involved in circulating tumor cell adhesion and interaction with other circulating cells, examine their functional constraints, and predict effects of inhibiting specific mechanisms.

Investigation of the essential role of platelet-tumor cell interactions in metastasis progression using an agent-based model.

Oligometastasis is a cancer disease state characterized by a limited number of metastatic tumors involving single or few organs and with biological properties that make them potentially amenable to locoregional antitumor therapy. Current clinical data show that they are potentially curable with surgical resection or/and radiotherapy. Yet, mechanisms of progression from primary tumor to oligometastasis, rather than to polymetastases, is lacking in detail. In the current review we focus on the role of micro-RNAs in the regulation of metastases development and the role they may play in the differentiation of oligometastatic from polymetastatic progression. We also discuss the analyses of metastatic samples from oligo-and polymetastatic patients, which suggest that oligometastasis is a distinct biologic entity regulated in part by micro-RNAs. In addition, a review of the known functions of oligometastatic-specific micro-RNAs suggest that they regulate multiple steps in the metastatic cascade, including epithelial-mesenchymal transition, tumor invasion, intravasation, distant vascular extravasation and proliferation in a distant organ. Understanding the role of micro-RNAs and their target genes in oligometastatic disease may allow for the development of targeted therapies to effectively conrol the spread of metastases.

Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs.

Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity.

14q32-encoded microRNAs mediate an oligometastatic phenotype.

We present a model of hepatic colorectal metastases which represents monoclonal cell lines double-labeled by luciferase and tdTomato. These cells form liver metastasis in varying numbers and patterns similar to those observed in patients. Using in vivo and ex vivo luminescent and fluorescent imaging we determine the growth kinetics and clonogenic frequency of tumor cells colonizing liver. Molecular profiling detected stable expressional differences between clones consistent with their phenotypes. The data indicate that clinically relevant phenotypes of liver metastases can be modeled in vivo.

Imaging of tumor clones with differential liver colonization.

Thyroid nodules incidentally identified on imaging are thought to contribute to the increasing incidence of thyroid cancer. We aim to determine the true rate of incidental thyroid nodule reporting, malignancy rates of these nodules, and to compare these findings with rates of detection by dedicated radiology review.

Benign and Malignant Thyroid Incidentalomas Are Rare in Routine Clinical Practice: A Review of 97,908 Imaging Studies.

The selection of patients for oligometastasis-directed ablative therapy remains a challenge. The authors report on clinical and molecular predictors of survival from a stereotactic body radiotherapy (SBRT) dose-escalation trial for oligometastases.

Article	Year
Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity. Molecular vision\| PubMed ID: 17615545	2007
Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model. Investigative ophthalmology & visual science\| PubMed ID: 18385079	2008
Direct imaging of optical cavity modes in ZnO rods using second harmonic generation microscopy. The journal of physical chemistry. A\| PubMed ID: 19588988	2010
New-onset maternal gestational hypertension and risk of retinopathy of prematurity. Investigative ophthalmology & visual science\| PubMed ID: 20463319	2010
Investigation of the essential role of platelet-tumor cell interactions in metastasis progression using an agent-based model. Theoretical biology & medical modelling\| PubMed ID: 24725600	2014
Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs. Clinical & experimental metastasis\| PubMed ID: 24968866	2014
14q32-encoded microRNAs mediate an oligometastatic phenotype. Oncotarget\| PubMed ID: 25686838	2015
Imaging of tumor clones with differential liver colonization. Scientific reports\| PubMed ID: 26094901	2015
Benign and Malignant Thyroid Incidentalomas Are Rare in Routine Clinical Practice: A Review of 97,908 Imaging Studies. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology\| PubMed ID: 26160694	2015
Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). Cancer\| PubMed ID: 27206146	2016

Abhineet Uppal

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