Invest. Ophthalmol. Vis. Sci.

2006

DOI: 10.1167/iovs.04-0882

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Orthotopic Human Choroidal Melanoma Xenografts in Nude Rats with Aggressive and Nonaggressive PAS Staining Patterns

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Abstract: It is possible to grow human choroidal melanoma orthotopic xenografts in nude rats that reproduce the PAS staining patterns associated with aggressive and nonaggressive choroidal melanomas in patients.

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Growth Of Ocm-1 Multicellular Layers (Mcl)1

Diffusion Modeling Of Po 2 Profiles1

Introduction1

Rat Model1

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Cited by 14 publications

(15 citation statements)

References 41 publications

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“…They were maintained in RPMI medium with antibiotic and 10% fetal bovine serum (FBS). 3-D clusters or spheroids can be grown from OCM-1 cells in vitro, but the spheroids are loose clusters of cells that are not truly spherical in nature (Braun and Abbas, 2006). MCL were grown as described by Hicks et al, with slight modifications (Cowan et al, 1996).…”

Section: Growth Of Ocm-1 Multicellular Layers (Mcl)mentioning

confidence: 99%

“…A final possibility is that this zero central PO 2 is a function of the MCL model. When grown as spheroids, the OCM-1 form loose, nonspherical 3-D clusters (Braun and Abbas, 2006). However, when seeded on the collagen-coated insert, the OCM-1 cells grew as a more tightly packed 3-D layer (Figure 1).…”

Section: Diffusion Modeling Of Po 2 Profilesmentioning

confidence: 99%

“…This process must be performed with the aid of a microscope (MuellerKlieser and Sutherland, 1982). Although spheroids are an excellent model for the study of oxygen transport in tumor parenchyma, symmetrical spheroids cannot be grown from all cell lines (Braun and Abbas, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Modeling of oxygen transport across tumor multicellular layers

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2007

Microvascular Research

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Purpose-Tumor oxygen level plays a major role in the response of tumors to different treatments. The purpose of this study was to develop a method of determining oxygen transport properties in a recently developed 3-D model of tumor parenchyma, the multicellular layer (MCL).Methods-OCM-1 human choroidal melanoma cells were grown as 3-D MCL on collagen-coated culture plate inserts. A recessed-cathode oxygen microelectrode was used to measure oxygen tension (PO 2 ) profiles across 8 different MCL from the free surface to the insert membrane. The profiles were fitted to four different one-dimensional diffusion models: 1-, 2-, and 3-region models with uniform oxygen consumption (q) in each region and a modified 3-region model with a central region where q=0 and PO 2 =0.Results-Depending upon the presence of a central region of anoxia, the PO 2 profiles were fitted best by either the two-region model or the modified 3-region model. Consumption of tumor cells near the insert membrane was higher than that of cells close to the free surface (33.1 ± 13.6 x 10 −4 vs. 11.8 ± 6.7 x 10 −4 mm Hg/m 2 , respectively). Conclusions-The model is useful for determining oxygenation and consumption in MCL, especially for cell lines that cannot be grown as spheroids. In the future, this model will permit the study of parameters important in tumor oxygenation in vitro.

“…They were maintained in RPMI medium with antibiotic and 10% fetal bovine serum (FBS). 3-D clusters or spheroids can be grown from OCM-1 cells in vitro, but the spheroids are loose clusters of cells that are not truly spherical in nature (Braun and Abbas, 2006). MCL were grown as described by Hicks et al, with slight modifications (Cowan et al, 1996).…”

Section: Growth Of Ocm-1 Multicellular Layers (Mcl)mentioning

confidence: 99%

“…A final possibility is that this zero central PO 2 is a function of the MCL model. When grown as spheroids, the OCM-1 form loose, nonspherical 3-D clusters (Braun and Abbas, 2006). However, when seeded on the collagen-coated insert, the OCM-1 cells grew as a more tightly packed 3-D layer (Figure 1).…”

Section: Diffusion Modeling Of Po 2 Profilesmentioning

confidence: 99%

“…This process must be performed with the aid of a microscope (MuellerKlieser and Sutherland, 1982). Although spheroids are an excellent model for the study of oxygen transport in tumor parenchyma, symmetrical spheroids cannot be grown from all cell lines (Braun and Abbas, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Modeling of oxygen transport across tumor multicellular layers

¹

2007

Microvascular Research

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Purpose-Tumor oxygen level plays a major role in the response of tumors to different treatments. The purpose of this study was to develop a method of determining oxygen transport properties in a recently developed 3-D model of tumor parenchyma, the multicellular layer (MCL).Methods-OCM-1 human choroidal melanoma cells were grown as 3-D MCL on collagen-coated culture plate inserts. A recessed-cathode oxygen microelectrode was used to measure oxygen tension (PO 2 ) profiles across 8 different MCL from the free surface to the insert membrane. The profiles were fitted to four different one-dimensional diffusion models: 1-, 2-, and 3-region models with uniform oxygen consumption (q) in each region and a modified 3-region model with a central region where q=0 and PO 2 =0.Results-Depending upon the presence of a central region of anoxia, the PO 2 profiles were fitted best by either the two-region model or the modified 3-region model. Consumption of tumor cells near the insert membrane was higher than that of cells close to the free surface (33.1 ± 13.6 x 10 −4 vs. 11.8 ± 6.7 x 10 −4 mm Hg/m 2 , respectively). Conclusions-The model is useful for determining oxygenation and consumption in MCL, especially for cell lines that cannot be grown as spheroids. In the future, this model will permit the study of parameters important in tumor oxygenation in vitro.

“…This model facilitated the observation of choroidal and tumor vessels with epifluorescence. Because the success rate was not as high as expected, Braun and colleagues [28,29,30] further improved this model by injecting spheroids of human cell lines into the suprachoroidal space to obtain tumor growth. Rats were sacrificed 4-41 days after inoculation, and melanomas were found in 96% of the animals.…”

Section: Rat Modelmentioning

confidence: 99%

Animal Eye Models for Uveal Melanoma

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2015

Ocul Oncol Pathol

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Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models.

“…We did not have accurate cell counts on these, but we estimate that they contained at least 5 x 10 6 cells. Since we have had success growing human choroidal melanomas orthotopically in the eyes of nude rats using spheroids, 4 we thought injection of spheroids might result in MDA-MB 231 tumor growth in the mammary gland. Unfortunately, no tumor growth was evident following implantation of MDA-MB 231 spheroids into the mammary glands of the nude rats.…”

Section: Progress On Taskmentioning

confidence: 99%

Use of Mitochondria-Specific Dye MKT-077 as a Radiosensitizer to Preoperatively Treat Locally Advanced Breast Cancer

2008

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. (From -To) REPORT DATE (DD-MM-YYYY) April 2006 REPORT TYPE Annual Summary DATES COVERED SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe major goal of this project is to determine if the rhodacyanine analog dye, MKT-077, can be used to inhibit breast cancer cell oxygen metabolism and raise tumor oxygen levels, thereby radiosensitizing the tumor. In the first year, we have performed in vitro experiments to determine drug uptake and subsequent MKT-077-induced metabolic inhibition in human MDA-MB 231 cells, as outlined in Tasks 1 and 2. We originally proposed to do this work in our multicellular layer (MCL) model of tumor parenchyma, but we had difficulty growing MCLs from this cell line consistently. Therefore, we have begun determining MKT-077 drug uptake and metabolic inhibition using MDA-MB 231 monolayers and cell suspensions. This approach has been successful, and we have been able to show that the cells rapidly take up the drug, which inhibits cellular oxygen metabolism by 22% at a dose of 4 µg/ml. We are currently completing the drug uptake studies and determining the inhibition caused by other doses. In addition, we have begun the in vivo work in nude rats. We have determined that the rats can tolerate a dose of 10 mg/kg MKT-077 infused at 1.25 mg/kg/min. Soon we will begin measuring MKT-077-induced oxygen changes in orthotopic xenografts in vivo.15. Subject Terms (keywords previously assigned to proposal abstract or terms which apply to this award)

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