Automated analysis of multimodal fluorescence lifetime imaging and optical coherence tomography data for the diagnosis of oral cancer in the hamster cheek pouch model.

It is known that the progression of oral cancer is accompanied by changes in both tissue biochemistry and morphology. A multimodal imaging approach combining functional and structural imaging modalities could therefore provide a more comprehensive prognosis of oral cancer. This idea forms the central theme of the current study, wherein this premise is examined in the context of a multimodal imaging system that combines fluorescence lifetime imaging (FLIM) and optical coherence tomography (OCT).

Automated classification of optical coherence tomography images for the diagnosis of oral malignancy in the hamster cheek pouch.

Most studies evaluating the potential of optical coherence tomography (OCT) for the diagnosis of oral cancer are based on visual assessment of OCT B-scans by trained experts. Human interpretation of the large pool of data acquired by modern high-speed OCT systems, however, can be cumbersome and extremely time consuming. Development of image analysis methods for automated and quantitative OCT image analysis could therefore facilitate the evaluation of such a large volume of data.

Developmental stage determines estrogen receptor alpha expression and non-genomic mechanisms that control IGF-1 signaling and mammary proliferation in mice.

Insulin like growth factor-1 (IGF-1) stimulates increased proliferation and survival of mammary epithelial cells and also promotes mammary tumorigenesis. To study the effects of IGF-1 on the mammary gland in vivo, we used BK5.IGF-1 transgenic (Tg) mice.

P53 genotype as a determinant of ER expression and tamoxifen response in the MMTV-Wnt-1 model of mammary carcinogenesis.

Clinical studies show that estrogen receptor-α (ER) expressing tumors tend to have better prognosis, respond to antiestrogen therapy and have wild-type p53. Conversely, tumors with inactivating mutations in p53 tend to have worse outcomes and to be ER-negative and unresponsive to antihormone treatment. Previous studies from our laboratory have shown that p53 regulates ER expression transcriptionally, by binding the ER promoter and forming a complex with CARM1, CBP, c-Jun, RNA polymerase II and Sp1.

Two hypomorphic alleles of mouse Ass1 as a new animal model of citrullinemia type I and other hyperammonemic syndromes.

Citrullinemia type I (CTLN1, OMIM# 215700) is an inherited urea cycle disorder that is caused by an argininosuccinate synthetase (ASS) enzyme deficiency. In this report, we describe two spontaneous hypomorphic alleles of the mouse Ass1 gene that serve as an animal model of CTLN1. These two independent mouse mutant alleles, also described in patients affected with CTLN1, interact to produce a range of phenotypes.

In vivo simultaneous morphological and biochemical optical imaging of oral epithelial cancer.

Early detection of cancer is key to reducing morbidity and mortality. Morphological and chemical biomarkers presage the transition from normal to cancerous tissue. We have developed a noninvasive imaging system incorporating optical coherence tomography (OCT) and fluorescence lifetime imaging microscopy (FLIM) into a single optical system for the first time, in order to acquire both sets of biomarkers.

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model.

We examined the wavelength dependence of ultraviolet (UV) ra-diation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish.

Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch.

This study was performed to examine the carcinogenic effects of benzo[a]pyrene (B[a]P) and manufactured gas plant (MGP) residues on the hamster cheek pouch (HCP). Syrian hamsters were treated topically with a suspension of 2%, 10%, or 20% B[a]P or 50% or 100% MGP-7 (a mixture of residues from 7 MGP sites) in mineral oil for eight (short-term study) and sixteen, twenty, twenty-eight, and thirty-two weeks (long-term study). The short-term study showed that B[a]P induced p53 protein accumulation, indicative of genotoxic damage, as well as increased cell proliferation, hyperplasia, and inflammation, which is usually associated with promotional activity.

Etiology of MNU-induced melanomas in Xiphophorus hybrids.

Genetic hybrids of the genus Xiphophorus have historically been useful models for study of the genetic aspects of tumor formation. In the most studied Xiphophorus tumor model, two-gene loci, XMRK and DIFF, are implicated as critical both to UV-induced and spontaneous melanoma formation in BC(1) hybrids of crosses between X. maculatus and X.

The genetic map of Xiphophorus fishes represented by 24 multipoint linkage groups.

Hybrids between distinct Xiphophorus species have been utilized for over 70 years to study melanoma and other neoplasms that can develop spontaneously in hybrid offspring. Genetic linkage mapping has proven to be important in delineating genomic areas that harbor oncogenes and tumor suppressors. Within this report, two parallel backcrosses have been utilized to generate a genetic linkage map for Xiphophorus fishes.

Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus.

Thymic epithelial cells (TECs) in adult mice have been classified into distinct subsets based on keratin expression profiles. To explore the emergence of TEC subsets during ontogeny, we analyzed keratin 8 and keratin 5 expression at several stages of fetal development in normal C57BL/6J mice. In addition, thymic epithelial development and compartmentalization were explored in recombination-activating gene 2/common cytokine receptor gamma-chain-deficient and Ikaros-null mice that sustain early and profound blocks in thymocyte differentiation.

Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation.

We previously described an autosomal-recessive mutation named nackt (nkt) exhibiting partial alopecia associated with CD4(+) T-cell deficiency. Also, we recently reported that nkt (now Ctsl(nkt)) comprises a deletion in the cathepsin L (Ctsl) gene. Another recent study reported that Ctsl knockout mice have CD4(+) T-cell deficiency and periodic shedding of hair, which recapitulate the nkt mutation and the old furless (fs) mutation.

Overexpression of a constitutively active form of c-src in skin epidermis increases sensitivity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.

Transgenic mice were developed to study the role of c-src in epithelial tumorigenesis through targeted expression of a constitutively active form of murine c-src (src(529)). Src(529) was targeted to the interfollicular epidermis with the human keratin 1 (HK1) promoter. The skin phenotype of these mice was characterized by exaggerated epidermal hyperplasia and hyperkeratosis within the first week after birth.