Natural History of Pancreatic Cancer Recurrence Following “Curative” Resection in Athymic Mice

Torgenson, Marcus; Shea, Jill E.; Firpo, Matthew A.; Dai, Qiang; Mulvihill, Sean J.; Scaife, Courtney L.

doi:10.1016/j.jss.2007.08.024

Cited by 11 publications

(20 citation statements)

References 19 publications

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“…The AsPC-1 cell line was somewhat more tumorigenic and produced a larger percentage of animals with peritoneal dissemination and lymph node metastases than did Panc-1 cells when animals were necropsied at time of morbidity or 100 days after implantation, consistent with the present findings in NSG mice. Torgenson et al 33 found that implantation of 1 × 10 6 MIA PaCa-2 and AsPC-1cells had similar growth characteristics at 2 and 5 weeks after orthotopic injection in nude mice (Ncr-Nu/Nu), whereas we found that AsPC-1 cells were somewhat more aggressive than MIA PaCa-2 cells in NSG mice. Further, Hotz et al 16 found that orthotopic injection of AsPC-1 cells resulted in 100% tumor development, whereas injection of MIA PaCa-2 cells resulted in 83% tumor take and progression of disease, consistent with the present results.…”

Section: Discussioncontrasting

confidence: 46%

Longitudinal Bioluminescence Imaging of Primary Versus Abdominal Metastatic Tumor Growth in Orthotopic Pancreatic Tumor Models in NSG Mice

Shannon¹,

Fishel

Xie

et al. 2015

Pancreas

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Objectives The purpose of the present study was to develop and validate noninvasive bioluminescence imaging methods for differentially monitoring primary and abdominal metastatic tumor growth in mouse orthotopic models of pancreatic cancer. Methods A semiautomated maximum entropy segmentation method was implemented for the primary tumor region-of-interest, and a rule-based method for manually drawing a region-of-interest for the abdominal metastatic region was developed for monitoring tumor growth in orthotopic models of pancreatic cancer. The two region-of-interest methods were validated by having two observers independently segment Panc-1 tumors, and the results compared with the number of mesenteric lymph node nodules, and histopathological assessment of liver metastases. The findings were extended to orthotopic tumors of the more metastatic MIA PaCa-2 and AsPC-1 cells where separate groups of animals were implanted with different numbers of cells. Results The results demonstrated that the segmentation methods were highly reliable, reproducible and robust, and allowed statistically significant discrimination in the growth rates of primary and abdominal metastatic tumors of different cell lines implanted with different numbers of cells. Conclusions The present results demonstrate that primary tumors and abdominal metastatic foci in orthotopic pancreatic cancer models can be reliably quantified separately and noninvasively over time with bioluminescence imaging.

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Section: Discussioncontrasting

confidence: 46%

Longitudinal Bioluminescence Imaging of Primary Versus Abdominal Metastatic Tumor Growth in Orthotopic Pancreatic Tumor Models in NSG Mice

Shannon¹,

Fishel

Xie

et al. 2015

Pancreas

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“…Katayama et al 89 observed that tumor masses were consistently higher for orthotopically injected MIA PaCa-2 than for HPAC cells when measured between 2 and 5 weeks. Another study showed that MIA PaCa-2 and AsPC-1 cells had similar growth characteristics at 2 and 5 weeks post orthotopic injection 90.…”

Section: Tumorigenicitymentioning

confidence: 97%

Phenotype and Genotype of Pancreatic Cancer Cell Lines

et al. 2010

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The dismal prognosis of pancreatic adenocarcinoma (PA) is due in part due to a lack of molecular information regarding disease development. Established cell lines remain a useful tool for investigating these molecular events. Here we present a review of available information on commonly used PA cell lines as a resource to help investigators select the cell lines most appropriate for their particular research needs. Information on clinical history, in vitro and in vivo growth characteristics, phenotypic characteristics, such as adhesion, invasion, migration and tumorigenesis, and genotypic status of commonly altered genes (KRAS, p53, p16, and SMAD4) was evaluated. Identification of both consensus and discrepant information in the literature suggests careful evaluation before selection of cell lines and attention be given to cell line authentication.

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“…Since PINCH has been shown to play a role in cell migration and signal transduction, PINCH expression may serve a potential marker for tumor invasion. Research on animal models and pancreatic human tissue revealed that PINCH expression is associated with a more aggressive pancreatic tumor and shorter survival57. We hypothesize that reduction of metastases in animals treated by Genexol PM or nbGEN and ultrasound may be associated with a concomitant reduction of PINCH expression due to the ultrasound effect on cell membranes.…”

Section: Discussionmentioning

confidence: 89%

Ultrasonic Nanotherapy of Pancreatic Cancer: Lessons from Ultrasound Imaging

et al. 2009

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Pancreatic ductal adenocarcinoma (PDA) is the fourth most common cause of cancer death in the United States, with a median survival time of only 3-6 months for forty percent of patients. Current treatments are ineffective and new PDA therapies are urgently needed. In this context, ultrasoundmediated chemotherapy by polymeric micelles and/or nanoemulsion/microbubble encapsulated drugs may offer an innovative approach to PDA treatment. PDA xenografts were orthotopically grown in the pancreas tails of nu/nu mice by surgical insertion of Red Fluorescence Protein (RFP)-transfected MiaPaCa-2 cells. Tumor growth was controlled by fluorescence imaging. Occasional sonographic measurements correlated well with the formal tumor tracking by red fluorescence. Tumor accumulation of paclitaxel-loaded nanoemulsion droplets and droplet-to-bubble transition under therapeutic ultrasound was monitored by diagnostic ultrasound imaging. MiaPaCa-2 tumors manifested resistance to treatment by Gemcitabine (GEM). This drug is the gold standard for PDA therapy. The GEM-resistant tumors proved sensitive to paclitaxel. Among six experimental groups studied, the strongest therapeutic effect was exerted by the following drug formulation: GEM + nanodroplet-encapsulated paclitaxel (nbGEN) combined with tumor-directed 1-MHz ultrasound that was applied for 30 s four to five hours after the systemic drug injection. Ultrasound-mediated PDA therapy by either micellar or nanoemulsion encapsulated paclitaxel resulted in substantial suppression of metastases and ascites suggesting ultrasound-enhanced killing of invasive cancerous cells. However, tumors relapsed after the completion of therapy, indicating survival of some tumor cells. The recurrent tumors manifested development of paclitaxel resistance. Ultrasound imaging suggested non-uniform distribution of nanodroplets in the tumor volume due to irregular vascularization, which may result in the development of zones with sub-therapeutic drug concentration. This is implicated as a possible cause of the resistance development, which may be pertinent to various modes of tumor nanotherapy.

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Natural History of Pancreatic Cancer Recurrence Following “Curative” Resection in Athymic Mice

Cited by 11 publications

References 19 publications

Longitudinal Bioluminescence Imaging of Primary Versus Abdominal Metastatic Tumor Growth in Orthotopic Pancreatic Tumor Models in NSG Mice

Longitudinal Bioluminescence Imaging of Primary Versus Abdominal Metastatic Tumor Growth in Orthotopic Pancreatic Tumor Models in NSG Mice

Phenotype and Genotype of Pancreatic Cancer Cell Lines

Ultrasonic Nanotherapy of Pancreatic Cancer: Lessons from Ultrasound Imaging

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