Validation of Ultrasonography to Evaluate Murine Orthotopic Oral Cavity Tumors

Pezold, John C.; Zinn, Kurt R.; Talbert, Melissa; Desmond, Renee; Rosenthal, Eben L.

doi:10.1159/000091324

Cited by 9 publications

(14 citation statements)

References 14 publications

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“…This mapping is in agreement with previous studies of the thyroid and tongue that charted these regions on a more limited level [36], [41]. Due to their inherent small size, an accurate, comprehensive in situ portrayal of mouse cervical lymph nodes is useful not only to mouse models of HNSCC, but other systems pertaining to illness causing cervical lymphadenopathy, including thyroid cancer [37], [38] and bacterial infection [42].…”

Section: Discussionsupporting

confidence: 89%

Use of High Frequency Ultrasound to Monitor Cervical Lymph Node Alterations in Mice

et al. 2014

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Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy.

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Section: Discussionsupporting

confidence: 89%

Use of High Frequency Ultrasound to Monitor Cervical Lymph Node Alterations in Mice

et al. 2014

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“…HFUS has been used to successfully visualize orthotopic HNSCC tumors 25 , and has the potential to monitor cervical node metastasis in mice with oral tumors 24 . In addition to ultrasound, bioluminescence imaging has also been used to visualize orthotopic oral tumor formation and cervical lymph node metastasis in live mice 26,27 .…”

Section: Discussionmentioning

confidence: 99%

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

Walk

McLaughlin

Weed

2015

JoVE

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High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 µm, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B)-mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non-invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease.

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“…Animals were placed in the supine position for examination with brightness mode (B-Mode) imaging (30 frames/s; 20 mm field of view; ref. 44). The final 300 images (10 s) of the B-mode study was saved.…”

Section: Methodsmentioning

confidence: 99%

Combination Treatment with TRA-8 Anti–Death Receptor 5 Antibody and CPT-11 Induces Tumor Regression in an Orthotopic Model of Pancreatic Cancer

DeRosier¹,

Buchsbaum

Oliver

et al. 2007

Clinical Cancer Research

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Purpose: Evaluate the response of human pancreatic cancer cell lines and orthotopic tumors to TRA-8, an agonistic antibody to death receptor 5, in combination with irinotecan (CPT-11). Experimental Design: MIA PaCa-2 and S2VP10 cells were treated withTRA-8 and/or CPT 11. Cell viability was determined by ATP assay. JC-1 mitochondrial depolarization and Annexin V assays confirmed cell death by apoptosis. Immunoblotting was used to evaluate protein changes. MIA PaCa-2 cells were injected into the pancreas of severe combined immunodeficient mice. Mice underwent abdominal ultrasound to quantitate tumor size before and after treatment with twice weekly injections of 200 Ag TRA-8 and/or 25 mg/kg CPT-11 for one or two treatment cycles, each lasting 2 weeks. Results: MIA PaCa-2 cells were more sensitive to TRA-8 and showed additive cytotoxicity, whereas S2VP10 cells showed synergistic cytotoxicity when treated with TRA-8 and CPT-11. Cell death occurred via apoptosis with increased cleavage of caspase-3, caspase-8, and caspase-9 and proapoptotic proteins Bid and poly(ADP)ribose polymerase after combination treatment compared with either agent alone. XIAP and Bcl-XL inhibitors of apoptosis were down-regulated. After a single cycle of in vivo combination therapy, tumor sizes had diminished significantly (P < 0.001) at 8 days posttreatment compared with no treatment, CPT-11, and TRA-8; and there was a 50-day increase in survival with combination treatment over untreated controls (P = 0.0002), 30 days over TRA-8, and a 36-day increase over CPT-11 monotherapy (P = 0.0003). With two cycles of TRA-8/CPT-11 treatment, mean survival time increased significantly (P < 0.001) to 169 days versus untreated controls, TRA-8 or 121, or 108 days, respectively). Conclusions: Combination TRA-8 and CPT-11 therapy produced enhanced cytotoxicity and survival in the MIA PaCa-2 orthotopic model of pancreatic cancer.

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Validation of Ultrasonography to Evaluate Murine Orthotopic Oral Cavity Tumors

Cited by 9 publications

References 14 publications

Use of High Frequency Ultrasound to Monitor Cervical Lymph Node Alterations in Mice

Use of High Frequency Ultrasound to Monitor Cervical Lymph Node Alterations in Mice

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

Combination Treatment with TRA-8 Anti–Death Receptor 5 Antibody and CPT-11 Induces Tumor Regression in an Orthotopic Model of Pancreatic Cancer

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