Uncovering and Correcting Shortcut Learning in Machine Learning Models for Skin Cancer Diagnosis.

Machine learning models have been successfully applied for analysis of skin images. However, due to the black box nature of such deep learning models, it is difficult to understand their underlying reasoning. This prevents a human from validating whether the model is right for the right reasons.

Papillomas at high risk for malignant progression arising both early and late during two-stage carcinogenesis in SENCAR mice.

The current study was designed to further establish that most papillomas produced in SENCAR mice during two-stage skin carcinogenesis are, in fact, premalignant lesions and to specifically determine the malignant conversion potential of papillomas that arise at different times during the carcinogenesis process. A method was established to physically map and monitor the lifespan of all papillomas produced in SENCAR mice during the course of an initiation-promotion experiment using DMBA as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The results from these experiments showed that in groups of mice initiated with either 0.

Effect of naturally occurring coumarins on the formation of epidermal DNA adducts and skin tumors induced by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in SENCAR mice.

Several naturally occurring coumarins previously found to be potent inhibitors of mouse hepatic ethoxyresorufin-O-deethylase (EROD) and/or pentoxyresorufin-O-dealkylase (PROD) were examined for their effects on formation of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) DNA adducts in mouse epidermis, as well as, their effects on skin tumor initiation by these polycyclic aromatic hydrocarbons (PAH). Bergamottin, a potent inhibitor of hepatic EROD, given topically 5 min prior to an initiating dose of B[a]P, significantly decreased total covalent binding of B[a]P to DNA in a dose-dependent manner 24 h after treatment. A dose of 400 nmol bergamottin reduced covalent binding of B[a]P by 72%.

Analysis of the ability of 12-O-tetradecanoylphorbol-13-acetate to induce epidermal hyperplasia, transforming growth factor-alpha, and skin tumor promotion in wa-1 mice.

Wa-1 mutant mice possess a defect in the production of transforming growth factor-alpha (TGF-alpha) that leads to a phenotype characterized by wavy hair and curly whiskers. In light of recent evidence indicating the importance of TGF-alpha in epithelial tumorigenesis, this study characterizes the responsiveness of wa-1 mice to skin tumor promotion by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). The responsiveness of wa-1 mice to TPA was compared with that of SENCAR and C57BL/6 mice, representing mouse lines highly sensitive and resistant to skin tumor promotion, respectively.

The effect of fluoro substituents on reactivity of 7-methylbenz[a]anthracene diol epoxides.

The present study has examined potential mechanisms for the influence of F-substituents on the biologic activity of methylbenz[a]anthracenes. DNA adducts derived from reaction of the racemic bay-region anti-diol epoxides of 7-methylbenz[a]anthracene, and its 9- and 10- fluoro derivatives, with calf thymus DNA in vitro were partially characterized. All three hydrocarbon diol epoxides produced similar DNA adduct profiles upon reaction with calf thymus DNA in vitro that were composed of two deoxyganosine and two deoxyadenosine adducts (tentatively identified as trans addition products).