Piperine Enhances the Anticancer Effects of Cisplatin on Tongue Squamous Cell Carcinoma Cell Line by Inducing Cell Apoptosis.

BACKGROUND: Oral squamous cell carcinoma is ranked as the predominant type of head and neck squamous cell carcinoma, comprising roughly 90% of all oral cancer cases. Natural products have proven to be highly valuable as complementary, or adjunctive in the treatment of cancer. Piperine, a natural compound derived from Piper nigrum, demonstrates anti-proliferative and anti-neoplastic effects across various types of cancer. This study focused on assessing the cytotoxic effect of piperine in conjunction with cisplatin within the OSCC cell line. METHODS: In this in-vitro study, cultured OSCC cells were divided into four groups: a control group (untreated), a group exposed solely to piperine, a group exposed solely to cisplatin, and a group receiving both piperine and cisplatin. Cell viability was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay technique. Additionally, flow cytometric analysis was employed to examine cell cycle progression and apoptosis. Assessment of reactive oxygen species activity, morphological changes, and nuclear area factor measurements were carried out. Expression of the apoptotic regulator Bax was assessed through western blotting analysis. RESULTS: Piperine has cytotoxic and apoptotic effects in a concentration-dependent manner. Piperine in combination with cisplatin exhibited a synergistic effect, resulting in more pronounced inhibition of cell viability in OSCC cells compared to using piperine and cisplatin alone. Piperine and cisplatin for 24 h induced apoptosis strongly by increasing Bax protein and ROS activity. CONCLUSION: Combining piperine with cisplatin demonstrated a greater effectiveness in triggering apoptosis in OSCC cells compared to using cisplatin alone, allowing for a reduction.

A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFß2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance.

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFß2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFß2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFß2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.

Chronic nonspecific cheilitis associated with tislelizumab treatment in a patient with a history of tongue squamous cell carcinoma: a case report.

BACKGROUND: Chronic nonspecific cheilitis is a complex condition characterized by persistent lip peeling and discomfort. This case report explores the clinical progression of a patient with history of tongue squamous cell carcinoma and subsequent Tislelizumab treatment, presenting with persistent lip peeling. CASE PRESENTATION: A patient with a history of tongue squamous cell carcinoma (T2N0M0), treated with chemotherapy, surgery, and Tislelizumab, presented with six months of persistent lip peeling. Clinical examination revealed distinct features of chronic nonspecific cheilitis with infectious angular cheilitis (Oral Candidiasis). A tailored treatment plan, emphasizing oral hygiene practices and local treatments with Sodium Bicarbonate, Tacrolimus ointment, and Chlortetracycline ointment. Follow-up visits demonstrated sustained improvement, highlighting the significance of individualized approaches. CONCLUSIONS: This case underscores the importance of recognizing and managing oral manifestations in patients with a history of cancer and immunotherapy. The patient's response to treatment suggests that a multifaceted approach, combining local therapy with lifestyle modifications, can be effective in managing chronic nonspecific cheilitis associated with immunotherapy. Routine follow-up appointments, guided by personalized medicine principles, contribute to sustained patient well-being.

Identification and validation of autophagy-related genes influenced by paris polyphylla in tongue cancer using network pharmacology.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) represents the most prevalent form of head and neck squamous cell carcinomas, comprising approximately one-third of all oral cancers. Paris polyphylla(PP) exhibit promising anti-tumor properties, yet their underlying mechanisms remain elusive. This study offers novel insights into the molecular mechanisms underlying TSCC treatment with PP and establishes a theoretical basis for their clinical application. METHODS: Employing transcriptomics and network pharmacology methodologies, we identified autophagy-related key genes associated with the effects of PP. These genes were subjected to KEGG and GO enrichment analyses to determine their related functions. In vitro, CAL-27 cells were treated with 10, 30, and 60 µg/ml of PP for 24 h to assess tumor cell proliferation, apoptosis, and autophagy-related markers. KEY FINDINGS: Molecular docking of MAPK3 and PSEN1 with PP revealed stable hydrogen bond interactions, indicating the therapeutic potential of these saponins in TSCC through the autophagy pathway. In vitro experiments demonstrated significant inhibition of proliferative activity in tongue squamous carcinoma CAL-27 cells and promotion of tumor cell apoptosis by PP. Western blot analysis confirmed alterations in the expression of autophagy markers P62, LC3B, and Beclin1 following treatment, suggesting activation of the autophagy pathway. CONCLUSIONS: Our results suggest that PP inhibits tumor cells through the autophagy pathway, in which MAPK3 and PSEN1 play a role as potential functional molecules.

[Inhibitory effect and mechanism of sodium cantharidate on human tongue squamous cell carcinoma CAL27 cells].

PURPOSE: To investigate the inhibitory effect of sodium cantharidate (SCA) on human tongue squamous cell carcinoma CAL27 cells and its mechanism. METHODS: CAL27 cells were pretreated with different concentrations of SCA. Cell viability was analyzed by CCK-8 method. The migration and invasion of CAL27 cells were measured by scratch test and Transwell chamber, and the apoptosis rate was measured by flow cytometry. p53 protein and its phosphorylation sites Ser33, Ser37, Ser46, expression of BCL-2, BAX, and cleaved caspase 3 in CAL27 cells were detected by Western blot. Statistical analysis was performed with Graphpad Prism 9.0 software package. RESULTS: Compared with the blank control group, the proliferation, migration and invasion of CAL27 cells in sodium cantharidate group were significantly decreased, and the apoptosis rate was significantly increased(P＜0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(P＜0.05 or P＜0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(P＜0.05 or P＜0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(P＜0.05 or P＜0.01). CONCLUSIONS: SCA can inhibit the proliferation, migration and invasion of human tongue squamous cell carcinoma CAL27 cells. It also down-regulates the ratio of BCL-2/BAX and up-regulates the expression of cleaved caspase 3 protein by regulating the phosphorylation of p53 protein, which induces apoptosis.

Experimental Study: The Development of a Novel Treatment for Chemotherapy-Resistant Tongue Cancer with the Inhibition of the Pathological Periostin Splicing Variant 1-2 with Exon 21.

Tongue squamous cell carcinoma (TSCC) occurs frequently in the oral cavity, and because of its high proliferative and metastatic potential, it is necessary to develop a novel treatment for it. We have reported the importance of the inhibition of the periostin (POSTN) pathological splicing variant, including exon 21 (PN1-2), in various malignancies, but its influence is unclear in tongue cancer. In this study, we investigated the potential of POSTN exon 21-specific neutralizing antibody (PN21-Ab) as a novel treatment for TSCC. Human PN2 was transfected into the human TSCC (HSC-3) and cultured under stress, and PN2 was found to increase cell viability. PN2 induced chemotherapy resistance in HSC-3 via the phosphorylation of the cell survival signal Akt. In tissues from human TSCC and primary tumors of an HSC-3 xenograft model, PN1-2 was expressed in the tumor stroma, mainly from fibroblasts. The intensity of PN1-2 mRNA expression was positively correlated with malignancy. In the HSC-3 xenograft model, CDDP and PN21-Ab promoted CDPP's inhibition of tumor growth. These results suggest that POSTN exon 21 may be a biomarker for tongue cancer and that PN21-Ab may be a novel treatment for chemotherapy-resistant tongue cancer. The treatment points towards important innovations for TSCC, but many more studies are needed to extrapolate the results.

Retinoic acid receptor-related orphan receptor alpha and synthetic RORα agonist against invasion and metastasis in tongue squamous cell carcinoma.

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.

An analysis on efficacy of applying ß-elemene intervention on chemically -induced tongue lesions using SAM algorithm.

An artificial intelligence (AI) model was designed to assist pathologists in diagnosing and quantifying structural changes in tongue lesions induced by chemical carcinogens. Using a tongue cancer model induced by 4-nitroquinoline-N-oxide and treated with ß-elemene, a total of 183 digital pathology slides were processed. The Segment Anything Model (SAM) was employed for initial segmentation, followed by conventional algorithms for more detailed segmentation. The epithelial contour area was computed using OpenCV's findcontour method, and the skeletonize method was used to calculate the distance map and skeletonized representation. The AI model demonstrated high accuracy in measuring tongue epithelial thickness and the number of papilla-like protrusions. Results indicated that the model group had significantly higher epithelial thickness and fewer papillae compared with the blank group. Furthermore, the treatment group exhibited reduced epithelial thickness and fewer papilla-like protrusions compared with the model group, though these differences were less pronounced. Overall, the SAM framework algorithm proved effective in quantifying tongue epithelial thickness and the number of papilla-like protrusions, thereby assisting healthcare professionals in understanding pathological changes and assessing treatment outcomes.

A novel bispecific peptide targeting PD-1 and PD-L1 with combined antitumor activity of T-cells derived from the patients with TSCC.

Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are key immune checkpoints (ICs) that critically influence immunotherapy. Tumor resistance to single IC-targeting drugs has increased interest in dual-target drugs, which have shown feasibility for cancer treatment. In this study, we aimed to develop dual-target peptide drugs targeting the PD-1/PD-L1 pathway and to evaluate their efficacy compared to functional antibodies in enhancing the cytotoxicity of human T cells against tongue squamous carcinoma cell lines. Through sequence analysis and peptide truncation, we modified a pre-existing peptide named nABPD-1 targeting PD-1. Subsequently, we obtained two novel peptides named nABPD-2 and nABPD-3, with nABPD-2 showing an enhanced affinity for human PD-1 protein compared to nABPD-1. Importantly, nABPD-2 exhibited dual-targeting capability, possessing a high affinity for both PD-L1 and PD-1. Furthermore, nABPD-2 effectively promoted the cytotoxicity of human T cells against tongue squamous carcinoma cell lines, surpassing the efficacy of anti-PD-1 or anti-PD-L1 functional antibodies alone. Considering that nABPD-2 has lower production costs and dose requirements, it can potentially be used in therapeutic applications.

In Vitro Assessment of the Cytotoxic Effect of 5-Fluorouracil, Thymoquinone and their Combination on Tongue Squamous Cell Carcinoma Cell Line.

BACKGROUND: Tongue cancer is the most prevalent type of oral cancer. Recently, natural compounds have been considered important resources for several anticancer drugs. Thymoquinone (TQ) exhibits a potent anti-cancer effect. 5-Fluorouracil (5-FU) is a chemotherapeutic drug that has been utilized in the treatment of cancer. Recently, combination therapy has gained popularity as a treatment option for patients with cancer. OBJECTIVES: The present study was carried out to assess the cytotoxic effect of 5-Fluorouracil (5-FU), Thymoquinone (TQ), and their combination on tongue squamous cell carcinoma cell line (HNO-97). METHODS: Tongue carcinoma cell line (HNO-97) was maintained in cultured flasks and the cells were divided into four groups; group Ι: control untreated group, group ΙΙ: HNO-97-treated cells with different concentrations of 5-FU from 0.5 µM/ml to 3µM/ml, group ΙIΙ: HNO-97-treated cells with different concentrations of TQ from 7.25µM/ml to 23.05µM/ml, and group ΙV: HNO-97-treated cells with both 5-FU and TQ in serial concentrations  till (IC50) in a dose of 27.44 µM/ml. Determination of the cytotoxic effect of the tested agents on the HNO-97 cell line was done using methyl thiazole tetrazolium assay, nuclear morphometric analysis, microscopic examination, and annexin-v/ propidium iodide staining assay. RESULT: The findings revealed that the cytotoxic effect of 5-FU, TQ, and their combination on tongue squamous cell carcinoma cell line (HNO-97) was dose-dependent. The microscopic examination revealed that 5-FU, TQ alone, or their combination induced apoptotic cell death. P-value < 0.05 was statistically significant. CONCLUSION: The combination of 5-FU and TQ produced a marked cytotoxic effect on HNO-97 cells.

Obesity enhances the response to neoadjuvant anti-PD1 therapy in oral tongue squamous cell carcinoma.

OBJECTIVES: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy. MATERIALS AND METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype. RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy. CONCLUSION: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.

Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

Capsaicin reverses cisplatin resistance in tongue squamous cell carcinoma by inhibiting the Warburg effect and facilitating mitochondrial-dependent apoptosis via the AMPK/AKT/mTOR axis.

Cisplatin is commonly used for the chemotherapy of tongue squamous cell carcinoma (TSCC); however, adverse side effects and drug resistance impact its therapeutic efficacy. Capsaicin is an active ingredient in chili peppers that exerts antitumor effects, whether it exerts antitumor effects on cisplatin-resistant cells remains unknown. Therefore, in this study, we investigated the effect of capsaicin on cisplatin resistance in TSCC cells and explored the underlying mechanisms. A cisplatin-resistant TSCC cell line was established by treated with increasing cisplatin concentrations. Combined treatment with cisplatin and capsaicin decreased the glucose consumption and lactate dehydrogenase activity and increased the adenosine triphosphate production both in vitro and in vivo, suggesting the inhibition of the Warburg effect. Moreover, this combined treatment induced cell apoptosis and significantly upregulated the levels of proapoptotic proteins, such as Bax, cleaved caspase-3, -7, and -9, and apoptosis-inducing factor. In contrast, levels of the antiapoptotic protein, Bcl-2, were downregulated. Additionally, LKB1 and AMPK activities were stimulated, whereas those of AKT and mTOR were suppressed. Notably, AMPK knockdown abolished the inhibitory effects of capsaicin and cisplatin on the AKT/mTOR signaling pathway and Warburg effect. Overall, combined treatment with capsaicin and cisplatin reversed cisplatin resistance by inhibiting the Warburg effect and facilitating mitochondrial-dependent apoptosis via the AMPK/AKT/mTOR axis. Our findings suggest combination therapy with capsaicin and cisplatin as a potentially novel strategy and highlight capsaicin as a promising adjuvant drug for TSCC treatment.

Suppression of N-Glycosylation of Zinc Finger Protein 471 Affects Proliferation, Invasion, and Docetaxel Sensitivity of Tongue Squamous Cell Carcinoma via Regulation of c-Myc.

Zinc finger protein 471 (ZNF471) is a member of the Krüppel-related domain zinc finger protein family, and has recently attracted attention because of its anti-cancer effects. N-glycosylation regulates expression and functions of the protein. This study aimed to investigate the effects of ZNF471 N-glycosylation on the proliferation, invasion, and docetaxel sensitivity of tongue squamous cell carcinoma (TSCC). It analyzed the expression, function, and prognostic significance of ZNF471 in TSCC using bioinformatics techniques such as gene differential expression analysis, univariate Cox regression analysis, functional enrichment analysis, and gene set enrichment analysis. Using site-specific mutagenesis, this study generated three mutant sites for ZNF471 N-glycosylation to determine the effect of N-glycosylation on ZNF471 protein levels and function. Quantitative real-time PCR, Western blot analysis, and immunohistochemistry tests confirmed the down-regulation of ZNF471 expression in TSCC. Low expression of ZNF471 is associated with poor prognosis of patients with TSCC. Overexpression of ZNF471 in vitro retarded the proliferation of TSCC cells and suppressed cell invasion and migration ability. Asparagine 358 was identified as a N-glycosylation site of ZNF471. Suppressing N-glycosylation of ZNF471 enhanced the protein stability and promoted the translocation of protein to the cell nucleus. ZNF471 binding to c-Myc gene promoter suppressed oncogene c-Myc expression, thereby playing the anti-cancer effect and enhancing TSCC sensitivity to docetaxel. In all, N-glycosylation of ZNF471 affects the proliferation, invasion, and docetaxel sensitivity of TSCC via regulation of c-Myc.

High-Performance Photodynamic Therapy of Tongue Squamous Cell Carcinoma with Multifunctional Nano-Verteporfin.

Background: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare. Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites. Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites. Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.

Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes.

BACKGROUND: Clinical indexes are often selected as relevant factors for constructing prognostic models of tongue squamous cell carcinoma (TSCC) patients, while factors related to therapeutic targets are less frequently included. As Apigenin (API) shows anti-tumor properties in many tumors, in this study, we construct a novel prognostic model for TSCC patients based on Apigenin-associated genes through transcriptomic analysis. METHODS: The effect of Apigenin (API) on the cell characteristics of TSCC cells was measured by several phenotype experiments. RNA-seq was executed to ensure differentially expressed genes (DEGs) in squamous cell carcinoma-9 (SCC-9) cells after API treatment. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to verify the expression of API-related genes. Then, combined with the gene expression data and relevant individual information of TSCC samples acquired from The Cancer Genome Atlas (TCGA), an API-related model was built through Lasso regression and multivariate Cox regression. A receiver operating characteristic (ROC) curve and a nomogram and calibration curve were created to forecast patient outcomes to improve the clinical suitability of the API-related signature. The relationships between the two risk groups and function enrichment, immune infiltration characteristics, and drug susceptibility were analyzed. RESULTS: We demonstrated that API could inhibit the malignant behavior of TSCC cells. Among API-related genes, TSCC cells treated with API, compared to the control group, have higher levels of transmembrane protein 213 (TMEM213) and G protein-coupled receptor 158 (GPR158), and lower levels of caspase 14 (CASP14) and integrin subunit alpha 5 (ITGA5). An 7 API-associated gene model was built through Lasso regression and multivariate Cox regression that could direct TSCC prognostic status and tumor immune cell infiltration. In addition, we acquired 6 potential therapeutic agents for TSCC based on the prognostic model. CONCLUSIONS: Our research suggested the inhibition effect of API on TSCC cells and provided a novel prognostic model combined with therapeutic factors that can guide the prognosis of TSCC and clinical decision-making in TSCC.

Naringenin-induced Oral Cancer Cell Apoptosis Via ROS-mediated Bid and Bcl-xl Signaling Pathway.

BACKGROUND: Oral cancer is a malignant tumor with a high impact and poor prognosis. Naringenin, a flavonoid found in citrus fruits and its anti-inflammatory and antioxidant properties offer potential therapeutic benefits. However, limited studies have been conducted on the impact of naringenin on human tongue carcinoma CAL-27 cells. This study aims to elucidate the correlation between naringenin and tongue cancer, thereby identifying a potential therapeutic candidate for drug intervention against tongue cancer. METHODS: The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot. RESULTS: The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS. CONCLUSION: The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.

Tertiary lymphoid structures in tongue cancer: Association with clinicopathological parameters, preoperative S-1 chemotherapy response, and prognosis.

BACKGROUND: Tertiary lymphoid structures (TLSs) are observed in cancer-invasive sites of various organs, and show evidence of tumor-specific B and/or T cells, suggesting an active humoral antitumor response. The aim of this study was to evaluate the relationship between TLSs and prognosis in patients with tongue squamous cell carcinoma (TSCC) after preoperative S-1 chemotherapy. METHODS: Among 196 TSCC cases, 111 patients who received preoperative S-1 chemotherapy were compared to 85 patients who did not receive chemotherapy. We investigated the incidence of TLSs in both preoperative biopsy and resected specimens. RESULTS: TLSs were present in 24 (12%) biopsy specimens and 31 (16%) resected specimens. TLSs were associated with clinicopathologically advanced cases and positivity for lymphatic invasion. None of the cases with pStage 0 (i.e., noninvasive cancer) showed TLSs. In preoperative S-1 chemotherapy cases, TLSs were significantly more common in those treated with S-1 for more than 21 days and in those with treatment effects 0, Ia, and Ib. TLSs may not be a favorable prognostic factor by themselves but maybe a prognostic factor when combined with preoperative S-1 treatment. CONCLUSION: The presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S-1 chemotherapy. The synergistic effect of S-1 by activating antitumor immunity may be associated with a better prognosis in TSCC patients with TLSs.

f25, a novel synthetic quinoline derivative, inhibits tongue cancer cell invasion and survival by the PPAR pathway in vitro and vivo.

Tongue cancer has a very high incidence in China, and there is a need to develop new anti-tumour drugs against it. We synthesised 31 novel quinoline derivatives to test their anti-tumour activity. A compound referred to as "f25" was identified through screening for its high in vitro toxicity against an oral squamous carcinoma cell line (CAL-27). f25 exhibited significant cytotoxicity against CAL-27 cells (IC50 = 7.70 ± 0.58 µΜ). f25 also inhibited the migration and invasion of CAL-27 cells to a level comparable with that of the chemotherapy agent cisplatin. Moreover, f25 promoted the apoptosis of CAL-27 cells. Transcriptome sequencing and western blotting showed that the mechanism of action of f25 against CAL-27 cells involved the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Specifically, f25 could bind to PPAR-α, PPAR-ß, and PPAR-γ and increase their expression. In vivo experiments showed that treatment with f25 led to a reduction in tumour volume in nude mice without significant toxicity. Overall, this study highlights the potential of quinoline compounds (particularly f25) for the design and synthesis of anti-tumour drugs. It also underscores the importance of the PPAR signalling pathway as a target for potential cancer therapies.

Efficacy of first-line immunization combined with antiangiogenesis treatment and chemotherapy for the treatment of tongue cancer: A case report.

BACKGROUND: There is currently no uniform and effective treatment for patients with locally advanced oral cancer who cannot tolerate surgery or radiotherapy. The prognosis of oral cancer patients with lymph node metastasis is very poor, but the clinical treatment of such patients faces certain challenges. PATIENTS AND METHODS: Case 1 was a 59-year-old patient with tongue cancer (cT 3 N x M 0 G 2) who refused radiotherapy because of a history of leukoderma. After evaluation of disease condition, a 4-drug combination therapy of toripalimab + anlotinib + nabpaclitaxel + carboplatin was administered. Case 2 was a 55-year-old patient with tongue cancer (cT 3 N 2 M 0 G 1) who could not receive radiotherapy because of a medical history of cervicofacial burns. After disease evaluation, toripalimab + anlotinib + docetaxel + carboplatin combination therapy was administered. CASE SUMMARY: Both patients did not experience any adverse reactions during treatment and achieved a complete response after 2 cycles of treatment. Their progression-free survival is currently 6 and 8 months, respectively, and they are in sustained remission. CONCLUSION: Currently, the efficacy of immune checkpoint inhibitors targeting programmed death-1 as a first-line treatment of inoperable and non-radiatable locally advanced oral cancer is unknown. Here, we describe 2 cases of locally advanced oral cancer treated with first-line immune checkpoint inhibitors in combination with targeted therapy and chemotherapy. This approach was successful in these patients, but a larger sample size is required to verify our findings.