minimally-invasive-establishment-murine-orthotopic-bladder

Minimally Invasive Establishment of Murine Orthotopic Bladder Xenografts

Orthotopic bladder cancer xenografts are the gold standard to study molecular cellular manipulations and new therapeutic agents&#160;in vivo. Suitable ...

University of British Columbia

High power, highly efficient single frequency oscillation of Er:YAG fiber-bulk hybrid laser at 1645 nm is demonstrated in actively and passively Q-switched operation modes. The slope efficiencies in the active and passive Q-switched operation reached 75% and 20%, respectively, with the record output powers in the narrow-linewidth and single longitudinal mode regimes of operation.

Highly efficient, narrow-linewidth, and single-frequency actively and passively Q-switched fiber-bulk hybrid Er:YAG lasers operating at 1645 nm.

A new flexible pump source, the optically-pumped semiconductor disk laser (SDL), for the Cr(2+):ZnSe laser is reported. The SDL provides up to 6W output power at a free running central wavelength of 1.98 microm. The Cr(2+):ZnSe laser operated at an output power of 1.8W and a slope efficiency of approximately 50% with respect to absorbed pump power whilst maintaining a low output intensity noise figure of <0.14% RMS. The system required no optical isolation even under the situation of significant optical feedback.

Semiconductor disk laser pumped Cr2+:Znse lasers.

Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23-37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.

Igor Moskalev

Department of Urologic Sciences

University of British Columbia

Minimally Invasive Establishment of Murine Orthotopic Bladder Xenografts

Igor Moskalev

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Urologic Sciences

University of British Columbia

Minimally Invasive Establishment of Murine Orthotopic Bladder Xenografts

Department of Urologic Sciences