Use of Transabdominal Ultrasound for the detection of intra-peritoneal tumor engraftment and growth in mouse xenografts of epithelial ovarian cancer

Abstract

ObjectiveTo evaluate intraperitoneal (IP) tumor engraftment, metastasis and growth in a pre-clinical murine epithelial ovarian cancer (EOC) model using both transabdominal ultrasound (TAUS) and bioluminescence in vivo imaging system (IVIS). MethodsTen female C57Bl/6J mice at six weeks of age were included in this study. Five mice underwent IP injection of 5x10 6 ID8-luc cells (+ D-luciferin) and the remaining five mice underwent IP injection of ID8-VEGF cells. Monitoring of tumor growth and ascites was performed weekly starting at seven days post-injection until study endpoint. ID8-luc mice were monitored using both TAUS and IVIS, and ID8-VEGF mice underwent TAUS monitoring only. Individual tumor implant dimension and total tumor volume were calculated. Average luminescent intensity was calculated and reported per mouse abdomen. Tumor detection was confirmed by gross evaluation and histopathology. All data are presented as mean +/-standard deviation. ResultsOverall, tumors were successfully detected in all ten mice using TAUS and IVIS, and tumor detection correlated with terminal endpoint histology/ H&E staining. For TAUS, the smallest confirmed tumor measurements were at seven days post-injection with mean long axis of 2.23mm and mean tumor volume of 4.17mm 3 . However, IVIS imaging was able to detect tumor growth at 14 days post-injection. Ascites formation was detected in mice at 21 days post-injection.

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

“…Despite all these models, establishing standardized, relevant, feasible, and reproducible PCa mice models remains a challenge. In general, peritoneal tumor burden or cancer progression in PCa mouse models can be quantified by (i) bioluminescence or biofluorescence: With the use of a tumor cell line engineered to express a reporter gene [ 22 , 23 ]; (ii) number and weight of peritoneal implants and/or omentum; iii) quantification of tumor burden by RT-PCR, immunohistochemistry, in vivo fluorescence microscopy, and flow cytometry, among other techniques [ 10 , 24 ]; (iv) ascites: Volume collected, hemorrhagic status; (v) survival: Mouse life span is evaluated by surveillance of spontaneous death or by euthanasia of animals with signs of pain or suffering according to established ethical protocol criteria [ 25 , 26 ]. Here, we provide a brief overview of reported mouse models to explore PCa in translational biomedical research ( Figure 1 ).…”

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

“…To this end, the following study paradigm ( Figure 1A ) was implemented wherein C57 BL/6J (BL/6) female mice at 6 weeks of age were provided water or antibiotic containing water (ABX; ampicillin, neomycin, metronidazole, and vancomycin) (23, 48), which was sustained for the duration of the study. After 2 weeks, mice were injected intraperitoneally (IP) with murine EOC lines ID8 or ID8-VEGF, syngeneic with BL/6 mice, and tumor growth was monitored by transabdominal ultrasound (TAUS) weekly for the course of the study (26). ID8 and ID8-VEGF cell lines were utilized as they are highly characterized and closely recapitulate human ovarian cancer progression.…”

“…For the ID8-LUC and ID8-VEGF cohorts, TAUS surveillance was initiated seven days following IP tumor injection as previously described (26). TAUS was performed every 10 days until study endpoint.…”

“…was sustained for the duration of the study. After 2 weeks, mice were injected intraperitoneally (IP) with murine EOC lines ID8 or ID8-VEGF, syngeneic with BL/6 mice, and tumor growth was monitored by transabdominal ultrasound (TAUS) weekly for the course of the study(26). ID8 and ID8-VEGF cell lines were utilized as they are highly characterized and closely recapitulate human ovarian cancer progression.…”

Targeting the Cx26/NANOG/Focal Adhesion Kinase Complex via Cell-Penetrating Peptides in Triple-Negative Breast Cancers

“…Bioluminescence images were taken with an IVIS Lumina (PerkinElmer) using D-luciferin as previously described 38 . Mice received an intraperitoneal (IP) injection of D-luciferin (Goldbio LUCK-1G, 150 mg/kg in 150 µL) under inhaled isoflurane anesthesia.…”