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Princess Margaret Cancer Centre

9 ARTICLES PUBLISHED IN JoVE

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Medicine

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics
Kelly Burrell 1, Sameer Agnihotri 1, Michael Leung 2, Ralph DaCosta 2, Richard Hill 2, Gelareh Zadeh 3
1Brain Tumor Research Centre, Hospital for Sick Children, Toronto Medical Discovery Tower, 2Ontario Cancer Institute, Princess Margaret Hospital, 3Neurosurgery, Toronto Western Hospital

We describe a novel in vivo imaging technique that couples fluorescent chimeric mice with intracranial windows and high-resolution 2-photon microscopy. This imaging platform aids studies of dynamic changes in brain tissue and microvasculature, at a single-cell level, following pathological insults and is adaptable to assess intracranial drug delivery and distribution.

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Bioengineering

One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles
Cheng S. Jin 1,2,3, Jonathan F. Lovell 4, Gang Zheng 1,2,3
1Department of Pharmaceutical Sciences, University of Toronto, 2The Institute of Biomaterials and Biomedical Engineering, University of Toronto, 3Ontario Cancer Institute, Campbell Family Institute For Cancer Research and Techna Institute, 4Department of Biomedical Engineering, University at Buffalo, The State University of New York

We developed novel intrinsic multifunctional nanovesicles called porphysomes, which have structure-dependent fluorescence self-quenching and unique photothermal properties, thus functioning as potent photothermal therapy agents. We formulated porphysomes using high pressure extrusion and investigated their photothermal therapy efficacy in a xenograft tumor model.

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Bioengineering

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance
Yannan N. Dou 1, Robert A. Weersink 2,5, Warren D. Foltz 5,6, Jinzi Zheng 5,6, Naz Chaudary 7, David A. Jaffray 2,3,4,5,6, Christine Allen 1
1Leslie Dan Faculty of Pharmacy, University of Toronto, 2Department of Radiation Oncology, University of Toronto, 3Medical Biophysics, University of Toronto, 4Institute of Biomaterials & Biomedical Engineering, University of Toronto, 5Techna Institute and Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, 6STTARR Innovation Center, University Health Network, 7Ontario Cancer Institute, University Health Network

AN MRI-compatible custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

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Immunology and Infection

Femur Window Chamber Model for In Vivo Cell Tracking in the Murine Bone Marrow
Yonghong Chen *1, Azusa Maeda *1,2, Jiachuan Bu 1, Ralph DaCosta 1,2,3
1Princess Margaret Cancer Centre, 2Department of Medical Biophysics, University of Toronto, 3Techna Institute, University Health Network

The protocol describes a novel murine femur window chamber model that can be used to track movement of cells in the femoral bone marrow in vivo. Intravital multiphoton fluorescence microscopy is used to image three components of the femoral bone marrow (vasculature, collagen matrix, and neutrophils) over time.

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Medicine

Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors
Shawn Stapleton 1,2,3, Daniel Mirmilshteyn 2, Jinzi Zheng 3,4, Christine Allen 2,4,5, David A. Jaffray 1,2,3,4,5,6
1Department of Medical Biophysics, University of Toronto, 2Leslie Dan Faculty of Pharmacy, University of Toronto, 3STTARR Innovation Centre, Princess Margaret Cancer Centre, 4Institute of Biomaterials and Biomedical Engineering, University of Toronto, 5Techna Institute, University Health Network, 6Radiation Medicine Program, Princess Margaret Cancer Centre

The heterogeneous intra-tumoral accumulation of liposomes has been linked to an abnormal tumor microenvironment. Herein methods are presented to measure tumor microcirculation by perfusion imaging and elevated interstitial fluid pressure (IFP) using an image-guided robotic system. Measurements are compared to the intra-tumoral accumulation of liposomes, determined using volumetric micro-CT imaging.

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Cancer Research

An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells
Lauren Philp 1,2, Harley Chan 3, Marjan Rouzbahman 4, Ariana Rostami 5, Lili Ding 6, Scott V. Bratman 5,6, Margarete K. Akens 5,7,8, Jonathan C. Irish 7,9,11, Marcus Q. Bernardini 10, Gang Zheng 5,11
1Institute of Medical Science, University of Toronto, 2Department of Obstetrics and Gynecology, University of Toronto, 3Guided Therapeutics Laboratory, TECHNA Institute, University Health Network, 4Department of Pathology, Princess Margaret Cancer Center, University Health Network, 5Department of Medical Biophysics, University of Toronto, 6Princess Margaret Cancer Center, University Health Network, 7Techna Institute, University Health Network, 8Department of Surgery, University of Toronto, 9Department of Otolaryngology, Head and Neck Surgery, University of Toronto, 10Division of Gynecologic Oncology, University of Toronto /Princess Margaret Cancer Center, University Health Network, 11Princess Margaret Cancer Center, University Health Network

This protocol presents a standardized method to grow VX2 cells in culture and to create an orthotopic VX2 model of endometrial cancer with retroperitoneal lymph node metastases in rabbits. Orthotopic endometrial cancer models are important for the pre-clinical study of novel imaging modalities for the diagnosis of lymph node metastases.

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Medicine

Synthesis and Characterization of Multi-Modal Phase-Change Porphyrin Droplets
Kimoon Yoo 1,2, Alexander Dhaliwal 1,2, Juan Chen 1, Paul S. Sheeran 3, Gang Zheng 1,2
1Princess Margaret Cancer Centre, 2Department of Medical Biophysics, University of Toronto, 3Philips Healthcare

In this protocol, methods for synthesizing and characterizing multi-modal phase-change porphyrin droplets are outlined.

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Immunology and Infection

Culturing Lymphocytes in Simulated Microgravity Using a Rotary Cell Culture System
Marieke de Korte 1,2, Armand Keating 1,2,4, Chen Wang 1,3
1Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, 2Krembil Research Institute, Toronto Western Hospital, University Health Network, 3Pathology and Lab Medicine, Hematopathology, Mount Sinai Hospital, Sinai Health Systems, 4Medical Oncology and Hematology, Princess Margaret Cancer Centre

This is a step-by-step guide for using a commercially available rotary cell culture system to culture lymphocytes in simulated microgravity using specialized disposable culture vessels. This culturing method may be applied to any suspension-type cell culture.

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Cancer Research

A Dorsal Skinfold Window Chamber Tumor Mouse Model for Combined Intravital Microscopy and Magnetic Resonance Imaging in Translational Cancer Research
W. Jeffrey Zabel *1, Nader Allam *1, Hector Alejandro Contreras Sanchez 1, Warren Foltz 2,3, Costel Flueraru 4, Edward Taylor 2,3, Alex Vitkin 1,2,3
1Department of Medical Biophysics, University of Toronto, 2Radiation Medicine Program, Princess Margaret Cancer Centre, 3Department of Radiation Oncology, University of Toronto, 4Advanced Electronic and Photonics Research Center, National Research Council of Canada

Translation of Intravital microscopy findings is challenged by its shallow depth penetration into tissue. Here we describe a dorsal window chamber mouse model that enables co-registration of intravital microscopy and clinically applicable imaging modalities (e.g., CT, MRI) for direct spatial correlation, potentially streamlining clinical translation of intravital microscopy findings.

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