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The study explored the effects of MT-DADMe-ImmA, an inhibitor of 5′-methylthioadenosine phosphorylase (MTAP), on head and neck cancer cell lines, particularly FaDu and Cal27. The treatment with MT-DADMe-ImmA and 5′-methylthioadenosine (MTA) increased MTA concentrations, decreased polyamines, and induced apoptosis in these cancer cells by causing mitochondrial dysfunction and changes in DNA methylation. The combination treatment was selective for cancer cells, sparing normal fibroblasts and MTAP-deficient breast cancer cells. In a mouse model, MT-DADMe-ImmA led to tumor remission without significant toxicity, suggesting its potential as a selective anticancer agent for tumors sensitive to reduced CpG island methylation.

The study explored the effects of activating the protooncogene c-Myc in the skin of transgenic mice, revealing that c-Myc activation led to rapid proliferation and disrupted differentiation of keratinocytes, resulting in conditions resembling precancerous lesions such as hyperplastic actinic keratosis. These changes were accompanied by angiogenesis and were reversible upon deactivation of c-Myc. Despite the potential for c-Myc to induce apoptosis, survival signals in the skin suppressed this effect, allowing for the development of benign, hyperproliferative lesions without progressing to malignancy. The study highlighted the role of c-Myc in skin homeostasis and its implications in skin carcinogenesis, suggesting that additional mutations would be necessary for malignant transformation.

The study demonstrated that Myc activation in transgenic mice led to the depletion of the epidermal stem cell compartment by altering adhesive interactions with the local microenvironment. This was evidenced by changes in gene expression, particularly the downregulation of genes related to cell adhesion and the extracellular matrix, such as integrins and collagens. Myc activation promoted differentiation into sebocytes and interfollicular epidermis rather than hair lineages, impairing cell adhesion, spreading, and motility. These effects were linked to decreased formation of hemidesmosomes and reduced expression of extracellular matrix proteins, contributing to delayed wound healing and altered keratinocyte behavior. The findings highlighted Myc's role in modulating stem cell behavior, impacting skin biology and diseases related to stem cell dysfunction.

The study demonstrated that overexpression of ornithine decarboxylase (ODC) in mouse skin was sufficient to promote tumor formation. Transgenic mice with high levels of ODC expression in epidermal keratinocytes were more susceptible to tumor initiation with a single low dose of carcinogen, and they did not require additional tumor promoters for tumor development. The research suggested that the primary target cells for chemical carcinogens in the skin were located in hair follicles, and that ODC overexpression could activate these cells to form epidermal tumors.

The study demonstrated that elevated levels of ornithine decarboxylase (ODC) and polyamines, when combined with a mutant Ha-ras gene, led to spontaneous tumor development in double transgenic mice. These mice, which were bred to carry both K6/ODC and v-Ha-ras transgenes, developed well-differentiated keratoacanthomas, some of which progressed to carcinomas within 2 months. The tumor development was dependent on ODC, as the use of the ODC inhibitor DFMO prevented tumor formation and caused regression. This indicated that ODC overexpression and activated Ha-ras were sufficient for malignant transformation, providing a model to study epithelial tumor development without chemical carcinogens or tumor promoters.

The study investigated the expression of ornithine decarboxylase (ODC) in mouse skin treated with the tumor promoter TPA. It was found that ODC expression was heterogeneous, with high levels predominantly in suprabasal cells around hair follicles shortly after TPA treatment. This expression was transient, disappearing within 16 to 24 hours, but persisted in some cells within benign papillomas a week after TPA application. Pretreatment with retinoic acid or cycloheximide inhibited ODC expression. The findings suggested that both normal and tumor tissues in mice exhibited varied ODC expression.

In this study, transgenic mice overexpressing spermidine/spermine N1-acetyltransferase (SSAT) experienced permanent hair loss by 3 weeks of age due to the overaccumulation of putrescine, which disrupted normal hair follicle development. Although these mice completed the first hair cycle normally, they showed early signs of hair follicle degeneration and failed to enter the second anagen phase, resulting in the replacement of hair follicles with dermal cysts and epidermal utriculi. Elevated putrescine levels were linked to continuous epithelial cell proliferation, potentially causing follicular cysts and epidermal thickening. Hybrid mice with both ornithine decarboxylase (ODC) and SSAT overexpression exhibited even higher putrescine levels and more severe skin issues. Interestingly, SSAT mice were more resistant to papilloma development in a skin carcinogenesis model, possibly due to the inability of tumor-promoting agents to induce ODC or increase skin spermidine levels. The study highlighted the crucial role of putrescine in hair follicle development and its excessive accumulation's contribution to the hairless phenotype.

The study reported a novel de novo pathogenic variant in the ODC1 gene in a 32-month-old Caucasian girl, marking the first human case with symptoms similar to those observed in a transgenic ODC1 mouse model. The identified heterozygous nonsense mutation in the ODC1 gene resulted in a premature termination of 14 amino acid residues at the protein's c-terminus. The patient exhibited phenotypic features such as developmental delay, alopecia, macrosomia, macrocephaly, spasticity, hypotonia, cutaneous vascular malformation, delayed visual maturation, and sensorineural hearing loss. Whole-exome sequencing and Sanger sequencing confirmed the mutation (c.1342 A>T), and elevated ODC protein and polyamine levels were found in the patient's red blood cells. The study suggested that the patient might benefit from treatment with α-difluoromethylornithine, an FDA-approved drug.

The study investigated the effects of cigarette smoke condensates (CSCs) on mouse skin, focusing on hyperplasia and inflammation as short-term biomarkers of tumor promotion. Using a truncated initiation-promotion protocol, the research assessed epidermal thickness, proliferative index, and ornithine decarboxylase (ODC) expression after CSC application. Results showed that CSCs increased these markers, with partial reversibility in interfollicular areas but sustained elevation in perifollicular regions. The study highlighted perifollicular ODC expression as a promising indicator for evaluating CSCs due to its rapid induction, low threshold, and potential to reflect irreversible changes, aligning with the notion that ODC expression is crucial for tumor promotion and that tumors primarily originate in the perifollicular epidermis.