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Paradoxical control of multifocal mammary oncogenesis by radiation therapy.

Oncoimmunology

December 2025

Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA.

In an immunocompetent mouse model of multifocal, metachronous HR mammary carcinogenesis, we have recently demonstrated that a superior control of primary neoplastic lesions by focal radiotherapy does not necessarily translate into improved oncosuppression at non-irradiated (pre)malignant tissues. These data point to a link between local tumor control by radiotherapy and systemic oncogenesis that remains to be fully understood.

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Background: Considering that peripheral blood biomarkers are prognostic predictors for several human tumors, this study aimed to comparatively analyze the association of hematological alterations with the incidence of epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) in male and female mice treated with 4-nitroquinoline-N-oxide (4NQO) and ethanol (EtOH).

Methods: 120 C57Bl/6J mice (60 males and 60 females) were allocated to four groups (n = 15). They were treated firstly either with 5 mg/mL propylene glycol (PPG) or 100 μg/mL 4NQO in the drinking water for 10 weeks, followed by sterilized water (HO) or 8% EtOH (v/v) for 15 weeks, as follows: PPG/HO, PPG/EtOH, 4NQO/HO, and 4NQO/EtOH (CEUA-UFU, #020/21).

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Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells.

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Oral squamous cell carcinoma (OSCC) is one the most prevalent head and neck cancers and represents a major cause of morbidity and mortality worldwide. The main established risk factors for OSCC include tobacco and alcohol consumption and betel quid chewing, which may contribute alone or in combination with other environmental factors to carcinogenesis. The oral microbiota is emerging as a key player in the establishment of the molecular and cellular mechanisms that may trigger or promote carcinogenesis, including in the oral cavity.

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Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules.

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