scholarly journals In Vivo Fluorescence Imaging and Urinary Monoamines as Surrogate Biomarkers of Disease Progression in a Mouse Model of Pheochromocytoma

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4149-4156 ◽  
Author(s):  
Martin Ullrich ◽  
Ralf Bergmann ◽  
Mirko Peitzsch ◽  
Marc Cartellieri ◽  
Nan Qin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Fluorescence Imaging ◽  
Fluorescence Intensity ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Small Animal ◽  
Whole Body

Abstract Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine-producing chromaffin cells. Especially for metastatic PHEO, the availability of animal models is essential for developing novel therapies. For evaluating therapeutic outcome in rodent PHEO models, reliable quantification of multiple organ lesions depends on dedicated small-animal in vivo imaging, which is still challenging and only available at specialized research facilities. Here, we investigated whether whole-body fluorescence imaging and monitoring of urinary free monoamines provide suitable parameters for measuring tumor progression in a murine allograft model of PHEO. We generated an mCherry-expressing mouse PHEO cell line by lentiviral gene transfer. These cells were injected subcutaneously into nude mice to perform whole-body fluorescence imaging of tumor development. Urinary free monoamines were measured by liquid chromatography with tandem mass spectrometry. Tumor fluorescence intensity and urinary outputs of monoamines showed tumor growth–dependent increases (P < .001) over the 30 days of monitoring post-tumor engraftment. Concomitantly, systolic blood pressure was increased significantly during tumor growth. Tumor volume correlated significantly (P < .001) and strongly with tumor fluorescence intensity (rs = 0.946), and urinary outputs of dopamine (rs = 0.952), methoxytyramine (rs = 0.947), norepinephrine (rs = 0.756), and normetanephrine (rs = 0.949). Dopamine and methoxytyramine outputs allowed for detection of lesions at diameters below 2.3 mm. Our results demonstrate that mouse pheochromocytoma (MPC)-mCherry cell tumors are functionally similar to human PHEO. Both tumor fluorescence intensity and urinary outputs of free monoamines provide precise parameters of tumor progression in this sc mouse model of PHEO. This animal model will allow for testing new treatment strategies for chromaffin cell tumors.

A method to follow tumor growth and tumor induced bone loss simultaneously over time, in vivo, using whole body bioluminescence fluorescence imaging

Bone ◽  
2011 ◽  
Vol 48 (1) ◽  
pp. S49-S50
Author(s):  
T.J.A. Snoeks* ◽  
A. Khmelinskii ◽  
I. Que ◽  
B. Lelieveldt ◽  
E.L. Kaijzel ◽  
...  
Keyword(s):  
Bone Loss ◽  
Tumor Growth ◽  
Fluorescence Imaging ◽  
Whole Body ◽  
Over Time

scholarly journals IMMU-31. QUANTITATIVE EVALUATION OF ROUTES OF ADMINISTRATION OF IMMUNOTHERAPEUTIC T CELLS TO ORTHOTOPIC GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii111-ii111
Author(s):  
Lan Hoang-Minh ◽  
Angelie Rivera-Rodriguez ◽  
Fernanda Pohl-Guimarães ◽  
Seth Currlin ◽  
Christina Von Roemeling ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
Adoptive T Cell Therapy ◽  
Whole Body ◽  
T Cell Therapy ◽  
Clinical Responses

Abstract SIGNIFICANCE Adoptive T cell therapy (ACT) has emerged as the most effective treatment against advanced malignant melanoma, eliciting remarkable objective clinical responses in up to 75% of patients with refractory metastatic disease, including within the central nervous system. Immunologic surrogate endpoints correlating with treatment outcome have been identified in these patients, with clinical responses being dependent on the migration of transferred T cells to sites of tumor growth. OBJECTIVE We investigated the biodistribution of intravenously or intraventricularly administered T cells in a murine model of glioblastoma at whole body, organ, and cellular levels. METHODS gp100-specific T cells were isolated from the spleens of pmel DsRed transgenic C57BL/6 mice and injected intravenously or intraventricularly, after in vitro expansion and activation, in murine KR158B-Luc-gp100 glioma-bearing mice. To determine transferred T cell spatial distribution, the brain, lymph nodes, heart, lungs, spleen, liver, and kidneys of mice were processed for 3D imaging using light-sheet and multiphoton imaging. ACT T cell quantification in various organs was performed ex vivo using flow cytometry, 2D optical imaging (IVIS), and magnetic particle imaging (MPI) after ferucarbotran nanoparticle transfection of T cells. T cell biodistribution was also assessed in vivo using MPI. RESULTS Following T cell intravenous injection, the spleen, liver, and lungs accounted for more than 90% of transferred T cells; the proportion of DsRed T cells in the brains was found to be very low, hovering below 1%. In contrast, most ACT T cells persisted in the tumor-bearing brains following intraventricular injections. ACT T cells mostly concentrated at the periphery of tumor masses and in proximity to blood vessels. CONCLUSIONS The success of ACT immunotherapy for brain tumors requires optimization of delivery route, dosing regimen, and enhancement of tumor-specific lymphocyte trafficking and effector functions to achieve maximal penetration and persistence at sites of invasive tumor growth.

Celecoxib and radioresistant glioblastoma-derived CD133+ cells: improvement in radiotherapeutic effects

2011 ◽  
Vol 114 (3) ◽  
pp. 651-662 ◽  
Author(s):  
Hsin-I Ma ◽  
Shih-Hwa Chiou ◽  
Dueng-Yuan Hueng ◽  
Lung-Kuo Tai ◽  
Pin-I Huang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Critical Role ◽  
Tumor Development ◽  
Primary Brain Tumor ◽  
Scid Mice ◽  
Therapeutic Effects ◽  
Glioblastoma Cells ◽  
Source Case ◽  
Cox 2

Object Glioblastoma, the most common primary brain tumor, has a poor prognosis, even with aggressive resection and chemoradiotherapy. Recent studies indicate that CD133+ cells play a key role in radioresistance and recurrence of glioblastoma. Cyclooxygenase-2 (COX-2), which converts arachidonic acid to prostaglandins, is over-expressed in a variety of tumors, including CD133+ glioblastomas. The COX-2–derived prostaglandins promote neovascularization during tumor development, and conventional radiotherapy increases the proportion of CD133+ cells rather than eradicating them. The aim of the present study was to investigate the role of celecoxib, a selective COX-2 inhibitor, in enhancing the therapeutic effects of radiation on CD133+ glioblastomas. Methods Cells positive for CD133 were isolated from glioblastoma specimens and characterized by flow cytometry, then treated with celecoxib and/or ionizing radiation (IR). Clonogenic assay, cell irradiation, cell cycle analysis, Western blot, and xenotransplantation were used to assess the effects of celecoxib alone, IR alone, and IR with celecoxib on CD133+ and CD133− glioblastoma cells. Three separate xenotransplantation experiments were carried out using 310 severe combined immunodeficient (SCID) mice: 1) an initial tumorigenicity evaluation in which 3 different quantities of untreated CD133– cells or untreated or pretreated CD133+ cells (5 treatment conditions) from 7 different tumors were injected into the striatum of 2 mice (210 mice total); 2) a tumor growth study (50 mice); and 3) a survival study (50 mice). For these last 2 studies the same 5 categories of cells were used as in the tumorigenicity (untreated CD133– cells, untreated or pretreated CD133+ cells, with pretreatment consisting of celecoxib alone, IR alone, or IR and celecoxib), but only 1 cell source (Case 2) and quantity (5 × 104 cells) were used. Results High levels of COX-2 protein were detected in the CD133+ but not the CD133− glioblastoma cells. The authors further demonstrated that 30 μM celecoxib was able to effectively enhance the IR effect in inhibiting colony formation and increasing IR-mediated apoptosis in celecoxib-treated CD133+ glioblastoma cells. Furthermore, reduction in radioresistance was correlated with the induction of G2/M arrest, which was partially mediated through the increase in the level of phosphorylated-cdc2. In vivo xenotransplant analysis further confirmed that CD133+-associated tumorigenicity was significantly suppressed by celecoxib treatment. Importantly, pretreatment of CD133+ glioblastoma cells with a combination of celecoxib and IR before injection into the striatum of SCID mice resulted in a statistically significant reduction in tumor growth and a statistically significant increase in the mean survival rate of the mice. Conclusions Celecoxib combined with radiation plays a critical role in the suppression of growth of CD133+ glioblastoma stemlike cells. Celecoxib is therefore a radiosensitizing drug for clinical application in glioblastoma.

scholarly journals Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model

2018 ◽  
Vol 25 (6) ◽  
pp. 677-686 ◽  
Author(s):  
Shani Avniel-Polak ◽  
Gil Leibowitz ◽  
Victoria Doviner ◽  
David J Gross ◽  
Simona Grozinsky-Glasberg
Keyword(s):  
Mouse Model ◽  
Tumor Growth ◽  
Mtor Inhibitors ◽  
Degradation Pathway ◽  
Neuroendocrine Neoplasms ◽  
Histopathological Analysis ◽  
Anti Cancer ◽  
Subcutaneous Xenograft ◽  
Rheumatic Drug

Patients with neuroendocrine neoplasms (NENs) often require systemic treatment, which is frequently limited by the emergence of drug resistance. mTOR inhibitors (mTORi), such as RAD001 (everolimus), have been shown to inhibit neoplasm progression. mTORi stimulates autophagy, a degradation pathway that might promote the survival of neoplasm cells that are exposed to anti-cancer therapy. Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppresses autophagy. Based on our previous results, we hypothesized that CQ may enhance the anti-tumorigenic effects of mTORi by inhibiting autophagy and we aimed to examine the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We established a NEN subcutaneous xenograft mouse model and evaluated the effect of the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. CQ alone and in combination with RAD001 significantly decreased neoplasm volume. Histopathological analysis revealed that the combination of CQ and RAD001 markedly inhibited mTOR activity and neoplasm cell growth, along with accumulation of autophagosomes and increased apoptosis. In conclusion, CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on neoplasm progression in patients with NENs, mainly in those treated with mTORi, are warranted.

scholarly journals Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shangli Zhu ◽  
Ming Yi ◽  
Yuze Wu ◽  
Bing Dong ◽  
Kongming Wu
Keyword(s):  
Tumor Progression ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Promising Target ◽  
Multiple Processes ◽  
Enhance Tumor Cell ◽  
Patient Prognosis ◽  
Anti Tumor Activity

AbstractMacrophages are heterogeneous cells that present as different functional phenotypes due to their plasticity. They can be classified into two categories, namely M1- and M2-like macrophages, which are involved in processes as diverse as anti-tumor activity and immunosuppressive tumor promotion. Tumor-associated macrophages (TAMs) are defined as being of an M2-type and are considered as the active component in tumor microenvironment. TAMs are involved in multiple processes of tumor progression through the expression of cytokines, chemokines, growth factors, protein hydrolases and more, which lead to enhance tumor cell proliferation, angiogenesis, and immunosuppression, which in turn supports invasion and metastasis. It is assumed that the abundance of TAMs in major solid tumors is correlated to a negative patient prognosis. Because of the currently available data of the TAMs’ role in tumor development, these cells have emerged as a promising target for novel cancer treatment strategies. In this paper, we will briefly describe the origins and types of TAMs and will try to comprehensively show how TAMs contribute to tumorigenesis and disease progression. Finally, we will present the main TAM-based therapeutic strategies currently available.

In vivo fluorescence imaging of E-selectin: Quantitative detection of endothelial activation in a mouse model of arthritis

2010 ◽  
Vol 63 (1) ◽  
pp. 107-117 ◽  
Author(s):  
Luke L. Gompels ◽  
Leigh Madden ◽  
Ngee Han Lim ◽  
Julia J. Inglis ◽  
Ellen McConnell ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fluorescence Imaging ◽  
Endothelial Activation ◽  
Quantitative Detection ◽  
In Vivo Fluorescence ◽  
In Vivo Fluorescence Imaging

scholarly journals Effects of Thymus vulgaris L., Cinnamomum verum J.Presl and Cymbopogon nardus (L.) Rendle Essential Oils in the Endotoxin-induced Acute Airway Inflammation Mouse Model

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3553
Author(s):  
Eszter Csikós ◽  
Kata Csekő ◽  
Amir Reza Ashraf ◽  
Ágnes Kemény ◽  
László Kereskai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Essential Oils ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Thymus Vulgaris ◽  
Inflammatory Conditions ◽  
Inflammatory Parameters

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential benefits or risks is low. Therefore, we analyzed the chemical composition and investigated the activity of TO, CO, and LO on airway functions and inflammatory parameters in an acute pneumonitis mouse model. The components of commercially available EOs were measured by gas chromatography–mass spectrometry. Airway inflammation was induced by intratracheal endotoxin administration in mice. EOs were inhaled during the experiments. Airway function and hyperresponsiveness were determined by unrestrained whole-body plethysmography on conscious animals. Myeloperoxidase (MPO) activity was measured by spectrophotometry from lung tissue homogenates, from which semiquantitative histopathological scores were assessed. The main components of TO, CO, and LO were thymol, cinnamaldehyde, and citronellal, respectively. We provide here the first evidence that TO and CO reduce inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters, so they can potentially be considered as adjuvant treatments in respiratory inflammatory conditions. In contrast, Ceylon type LO inhalation might have an irritant effect (e.g., increased airway hyperresponsiveness and MPO activity) on the inflamed airways, and therefore should be avoided.

scholarly journals Oral Administration of Fermented Papaya (FPP®) Controls the Growth of a Murine Melanoma through the In Vivo Induction of a Natural Antioxidant Response

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 118 ◽  
Author(s):  
Mariantonia Logozzi ◽  
Davide Mizzoni ◽  
Rossella Di Raimo ◽  
Daniele Macchia ◽  
Massimo Spada ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Potential Role ◽  
Tumor Development ◽  
Natural Antioxidants ◽  
Antioxidant Response ◽  
Blood Levels ◽  
Sublingual Administration ◽  
Anti Oxidant ◽  
The Sacrifice

Prolonged oxidative stress may play a key role in tumor development. Antioxidant molecules are contained in many foods and seem to have a potential role in future anti-tumor strategies. Among the natural antioxidants the beneficial effect of Fermented Papaya (FPP®) is well known. The aim of this study was to investigate the effects of orally administered FPP® in either the prevention or treatment of a murine model of melanoma. The tumor growth was analyzed together with the blood levels of both oxidants (ROS) and anti-oxidants (SOD-1 and GSH). The results showed that FPP® controlled tumor growth, reducing the tumor mass of about three to seven times vs. untreated mice. The most significant effect was obtained with sublingual administration of FPP® close to the inoculation of melanoma. At the time of the sacrifice none of mice treated with FPP® had metastases and the subcutaneous tumors were significantly smaller and amelanotic, compared to untreated mice. Moreover, the FPP® anti-tumor effect was consistent with the decrease of total ROS levels and the increase in the blood levels of GSH and SOD-1. This study shows that a potent anti-oxidant treatment through FPP® may contribute to both preventing and inhibiting tumors growth.

scholarly journals In vivo Retinal Fluorescence Imaging With Curcumin in an Alzheimer Mouse Model

2020 ◽  
Vol 14 ◽  
Author(s):  
Ahmad Sidiqi ◽  
Daniel Wahl ◽  
Sieun Lee ◽  
Da Ma ◽  
Elliott To ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fluorescence Imaging
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