Objectives Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. Methods Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. Results In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. Conclusion Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.

Oral leukoplakia (OL) is the most common potentially malignant oral disorder, with variable risk of progression to oral squamous cell carcinoma (OSCC). This study evaluated the chemopreventive and immunomodulatory potential of Artemisinin (ART) and Rubus occidentalis (RO), alone or combined (ARO), in a 4NQO-induced murine model. Mice received 4NQO (100 µg/mL) in drinking water, and treatments began at week 8. Animals were euthanized at weeks 12 and 16 for histological, apoptotic (caspases-3, -8, -9; calreticulin), inflammatory (IL-1β, IL-10, HMGB1), and immune (CD8, CD68, CD56, IFN-γ, GM-CSF) marker analyses. RO-treated animals showed delayed malignant transformation, with no carcinomas at week 16 and increased expression of caspase-9, calreticulin, HMGB1, IFN-γ, and GM-CSF, indicating transient activation of antitumor immune responses. ART-treated mice showed increased CD68 and reduced CD56 expression, suggesting an immunosuppressive profile and higher carcinoma incidence. The ARO combination did not improve outcomes beyond ART alone. These findings support the immunomodulatory and pro-apoptotic effects of RO in delaying OL progression, highlighting its chemopreventive potential. ART showed limited benefit under current conditions, warranting further investigation into dose optimization and synergistic strategies.

Objectives: Tobacco has been associated with the development of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). This study aimed to evaluate the in vitro and in vivo changes caused by carcinogen 4-nitroquinoline 1-oxide (4NQO), simulating smoking conditions. Materials and Methods: In the in vitro study, normal keratinocytes were exposed to 1.3 µM and 2.6 µM concentrations of 4NQO to induce dysplastic transformation (H-DISP) and malignant transformation (H-SCC), respectively. The cells were collected and subjected to hematoxylin and eosin (H&E) staining and immunocytochemistry with Ki-67. For the in vivo study, female C57BL/6J mice were divided into a pure control (PC) group and experimental groups exposed to 50 µg/mL (NQ) and 100 µg/mL (CM) of 4NQO in autoclaved drinking water. Each group was euthanized after 8, 12, 16, and 20 weeks of exposure. The tongues were collected, processed, stained with H&E, and analyzed using conventional light microscopy. Results: In vitro, significant morphological changes were observed in the H-DISP and H-SCC groups, with a cell proliferation index exceeding 30% in the H-DISP group. In vivo, the CM group showed greater progression to severe dysplasia/carcinoma within a shorter treatment period compared to the NQ group. Conclusions: We established critical doses and exposure durations for 4NQO, both in vitro and in vivo, to induce cellular changes and the formation of OL and OSCC, providing a standardized model for studies related to oral carcinogenesis.

This case series describes three midline odontogenic keratocysts (OKCs) and reviews the associated literature. All three patients were male; two lesions were maxillary. All lesions were surgically excised, with no recurrence. A search of PubMed, Embase, and Scopus identified 33 reported cases of midline OKC, including this series. Of these, 64% (21/33) were male, and age ranged from 6 to 80 years (mean 39.8 ± 20.3). The mandible was affected in 67% (22/33). Excision was the predominant treatment (94%, 31/33), with adjunctive cauterization in 30% (10/33) and decompression in 15% (5/33). Among cases with available follow‐up, one recurrence was reported. OKC should be considered in the differential diagnosis of midline jaw lesions, supported by combined clinical, radiographic, and histopathological assessment.