Princess Margaret Cancer Centre

9 ARTICLES PUBLISHED IN JoVE

Medicine

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

Kelly Burrell¹, Sameer Agnihotri¹, Michael Leung², Ralph DaCosta², Richard Hill², Gelareh Zadeh³

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.

Bioengineering

One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles

Cheng S. Jin^1,2,3, Jonathan F. Lovell⁴, 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.

Bioengineering

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Yannan N. Dou¹, Robert A. Weersink^2,5, Warren D. Foltz^5,6, Jinzi Zheng^5,6, Naz Chaudary⁷, David A. Jaffray^2,3,4,5,6, Christine Allen¹

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.

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 Bu¹, 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.

Medicine

Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors

Shawn Stapleton^1,2,3, Daniel Mirmilshteyn², 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.

Cancer Research

An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells

Lauren Philp^1,2, Harley Chan³, Marjan Rouzbahman⁴, Ariana Rostami⁵, Lili Ding⁶, Scott V. Bratman^5,6, Margarete K. Akens^5,7,8, Jonathan C. Irish^7,9,11, Marcus Q. Bernardini¹⁰, 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.

Medicine

Synthesis and Characterization of Multi-Modal Phase-Change Porphyrin Droplets

Kimoon Yoo^1,2, Alexander Dhaliwal^1,2, Juan Chen¹, Paul S. Sheeran³, 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.

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.

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 Sanchez¹, Warren Foltz^2,3, Costel Flueraru⁴, 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.