Development of a model of tissue with potentially malignant disorders (PMD) in the hamster cheek pouch to explore the long-term potential therapeutic and/or toxic effects of different therapeutic modalities

Heber, Elisa M.; Hughes, Andrea Monti; Pozzi, Enrique J. Sánchez; Itoiz, M. E.; Aromando, Romina F.; Molinari, Ana J.; Garabalino, Marcela A.; Nigg, David W.; Trivillin, Verónica A.; Schwint, Amanda E.

doi:10.1016/j.archoralbio.2009.10.010

Cited by 23 publications

(31 citation statements)

References 31 publications

(48 reference statements)

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“…Regarding the development of novel tumors (i.e., tumors not present at the end of the carcinogenesis protocol) from precancerous tissue, 100% of the animals in the control group exhibited novel tumors at 4 wk follow-up (41). In contrast, 64% of the hamsters in the one-treatment protocol at 4 wk follow-up developed novel tumors, whereas approximately 75-80% of the hamsters in the two-treatment protocol (at the longest follow-up time in each case) developed novel tumors.…”

Section: Resultsmentioning

confidence: 99%

“…The severity of mucositis was evaluated semiquantitatively in dose-limiting precancerous tissue as previously described (3, 50, 51) (SI Materials and Methods, S4). To evaluate the potential inhibitory effect of the different BNCT protocols on the development of novel tumors (i.e., tumors not present at the end of the carcinogenesis protocol) from precancerous tissue in this model, we used the percentage of hamsters with novel tumors in the treated pouch as a representative end point (SI Materials and Methods, S5) (3,41).…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Heber

Hawthorne

Kueffer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The application of boron neutron capture therapy (BNCT) mediated by liposomes containing 10 B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH 3 (CH 2 ) 15 -7,8-C 2 B 9 H 11 ] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na 3 [ae-B 20 H 17 NH 3 ] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.oncology | cancer | boronated liposomes | BNCT | neutron radiation

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Heber

Hawthorne

Kueffer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…We developed a novel model of precancerous tissue to evaluate the long-term (8 months follow-up) therapeutic/toxic effects of different therapeutic modalities. 18 To provide additional complementary information to characterize the degree of toxicity observed in the irradiated pouch, DIRI was utilized during the follow-up of the animals irradiated under different conditions.…”

Section: Hamster Cheek Pouch Oral Cancer Modelmentioning

confidence: 99%

Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy

et al. 2011

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Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10 B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals.We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution.We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

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“…Morris [5] improved and standardized this protocol for tumor induction, using DMBA at 0.5% and 5 weeks old hamsters. Recently, Heber et al [6] have established a protocol, obtaining tumors in 90% of the buccal pouches treated with DMBA for 12 weeks.…”

Section: Introductionmentioning

confidence: 99%

The Promoting Effect of Carbamide Peroxide Teeth Bleaching Gel in a Preclinical Model of Head and Neck Cancer in Hamster Buccal Pouch

Bampi

Vilela

Gonçalves

et al. 2014

Clin Exp Otorhinolaryngol

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ObjectivesThe aim of this study was to verify the promoting effect of carbamide peroxide on dimethylbenzanthracene (DMBA)-induced carcinogenesis in the hamster buccal pouch, in order to reduce the period of latency for tumor formation.MethodsSixteen hamsters were randomized into two groups of eight animals each. The hamsters of the group I had their right buccal pouches treated with 0.5% DMBA and 10% carbamide peroxide teeth bleaching gel for 55 days. The animals of the group II had their right pouches treated only with DMBA. After, six animals of each group had their pouches prepared for light microscopy. Histomorphometry was performed to assess the presence of keratinization, nuclear polymorphism, pattern of invasion, number of blood vessels, and inflammatory infiltrate in the tumor front. Furthermore, the newly formed lesions were graded according the Bryne's grading system. The remaining animals had the vascular system of the pouches casted by Mercox and qualitatively analyzed by scanning electron microscopy.ResultsHistopathological analysis of the buccal pouches treated with DMBA and carbamide peroxide exhibited formation of squamous cell carcinoma well-differentiated with a high degree of malignancy in all pouches. The development of this neoplasm was associated with a significant increase in the number of blood vessels, presence of keratin pearls, and inflammatory infiltrate. The pouches of the group II showed inflammation, epithelial hyperplasia, dysplasia, and squamous cell carcinoma in only three right pouches. The analysis of the electron micrographs of the pouches chemically inducted with DBMA and carbamide peroxide reveled formation of a new vascular network characteristic of squamous cell carcinoma.ConclusionThe protocol presented here, using DMBA associated with carbamide peroxide, shortens the period of latency to produce squamous cell carcinoma in the hamster buccal pouch, decreasing the time and costs of the experiments.

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Development of a model of tissue with potentially malignant disorders (PMD) in the hamster cheek pouch to explore the long-term potential therapeutic and/or toxic effects of different therapeutic modalities

Cited by 23 publications

References 31 publications

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy

The Promoting Effect of Carbamide Peroxide Teeth Bleaching Gel in a Preclinical Model of Head and Neck Cancer in Hamster Buccal Pouch

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