Identification of high-risk cutaneous melanoma tumors is improved when combining the online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31-gene expression profile-based classification.

Background: A significant proportion of patients with American Joint Committee on Cancer (AJCC)-defined early-stage cutaneous melanoma have disease recurrence and die. A 31-gene expression profile (GEP) that accurately assesses metastatic risk associated with primary cutaneous melanomas has been described.

Objective: We sought to compare accuracy of the GEP in combination with risk determined using the web-based AJCC Individualized Melanoma Patient Outcome Prediction Tool.

Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal.

Evidence suggests that aldehydic molecules generated during lipid peroxidation (LPO) are causally involved in most pathophysiological processes associated with oxidative stress. 4-Hydroxy-2-nonenal (4-HNE), the LPO-derived product, is believed to be responsible for much of the cytotoxicity. To counteract the adverse effects of this aldehyde, many tissues have evolved cellular defense mechanisms, which include the aldehyde dehydrogenases (ALDHs).

Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.

Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes.

Duane retraction syndrome, nystagmus, retinal pigment epitheliopathy and epiretinal membrane with micro- and pachygyria, developmental delay, hearing loss and craniopharyngioma.

Purpose: To report the association of Duane syndrome with nystagmus and a patterned hyperpigmentation of the retinal pigment epithelium, developmental delay, micro- and pachygyria and craniopharyngioma.

Case Report: We describe a 12-year old girl with developmental delay, hearing loss, cortical micro- and pachygyria, and a cystic craniopharyngioma; her ocular features include unilateral Duane syndrome, monocular nystagmus under binocular conditions, and a patterned hyperpigmentation of the retinal pigment epithelium. Her mother had similar retinal pigment epithelial abnormalities.

The role of corneal crystallins in the cellular defense mechanisms against oxidative stress.

The refracton hypothesis describes the lens and cornea together as a functional unit that provides the proper ocular transparent and refractive properties for the basis of normal vision. Similarities between the lens and corneal crystallins also suggest that both elements of the refracton may also contribute to the antioxidant defenses of the entire eye. The cornea is the primary physical barrier against environmental assault to the eye and functions as a dominant filter of UV radiation.

Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice.

ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower (catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(-/-)/Aldh3a1(-/-) double knock-out and Aldh1a1(-/-) and Aldh3a1(-/-) single knock-out mice were evaluated for biochemical changes and cataract formation (lens opacification). The Aldh1a1/Aldh3a1- and Aldh3a1-null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age.

Antioxidant function of corneal ALDH3A1 in cultured stromal fibroblasts.

Aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in epithelial cells and stromal keratocytes of mammalian cornea and is believed to play an important role in cellular defense. To explore a potential protective role against oxidative damage, a rabbit corneal fibroblastic cell line (TRK43) was stably transfected with the human ALDH3A1 and subjected to oxidative stress induced by H(2)O(2), mitomycin C (MMC), or etoposide (VP-16). ALDH3A1-transfected cells were more resistant to H(2)O(2,) MMC, and VP-16 compared to the vector-transfected cells.

Gene array profiles of alcohol and aldehyde metabolizing enzymes in brains of C57BL/6 and DBA/2 mice.

Background: Differences in ethanol metabolizing enzymes expressed in brain have been suggested to contribute to the significant differences in ethanol (alcohol) preference between inbred C57BL/6 and DBA/2 mouse strains.

Methods: We have utilized 2 different platforms of oligonucleotide microarray technology (CodeLink UniSet I BioArray from G.E.

ALDH3A1: a corneal crystallin with diverse functions.

Aldehyde dehydrogenase 3A1 (ALDH3A1) comprises a surprisingly high proportion (5-50% depending on species) of the water-soluble protein of the mammalian cornea, but is present little if at all in the cornea of other species. Mounting experimental evidence demonstrates that this abundant corneal protein plays an important role in the protection of ocular structures against oxidative damage. Corneal ALDH3A1 appears to protect against UV-induced oxidative stress through a variety of biological functions such as the metabolism of toxic aldehydes produced during the peroxidation of cellular lipids, the generation of the antioxidant NADPH, the direct absorption of UV-light, the scavenging of reactive oxygen species (ROS), and the possession of chaperone-like activity.

Arachidonic acid suppresses growth of human lung tumor A549 cells through down-regulation of ALDH3A1 expression.

Expression of aldehyde dehydrogenase 3A1 (ALDH3A1) in certain normal and tumor cells is associated with protection against the growth inhibitory effect of reactive aldehydes generated during membrane lipid peroxidation. We found that human lung tumor (A549) cells, which express high levels of ALDH3A1 protein, were significantly less susceptible to the antiproliferative effects of 4-hydroxynonenal compared to human hepatoma HepG2 or SK-HEP-1 cells that lack ALDH3A1 expression. However, A549 cells became susceptible to lipid peroxidation products when they were treated with arachidonic acid.