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Biomedicine & Pharmacotherapy =... Sep 2023Oral cancer is a neoplastic disorder of the oral cavities, including the lips, tongue, buccal mucosa, and lower and upper gums. Oral cancer assessment entails a... (Review)
Review
Oral cancer is a neoplastic disorder of the oral cavities, including the lips, tongue, buccal mucosa, and lower and upper gums. Oral cancer assessment entails a multistep process that requires deep knowledge of the molecular networks involved in its progression and development. Preventive measures including public awareness of risk factors and improving public behaviors are necessary, and screening techniques should be encouraged to enable early detection of malignant lesions. Herpes simplex virus (HSV), human papillomavirus (HPV), Epstein-Barr virus (EBV), and Kaposi sarcoma-associated herpesvirus (KSHV) are associated with other premalignant and carcinogenic conditions leading to oral cancer. Oncogenic viruses induce chromosomal rearrangements; activate signal transduction pathways via growth factor receptors, cytoplasmic protein kinases, and DNA binding transcription factors; modulate cell cycle proteins, and inhibit apoptotic pathways. In this review, we present an up-to-date overview on the use of nanomaterials for regulating viral proteins and oral cancer as well as the role of phytocompounds on oral cancer. The targets linking oncoviral proteins and oral carcinogenesis were also discussed.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Retroviridae; Mouth Neoplasms; Risk Factors
PubMed: 37364477
DOI: 10.1016/j.biopha.2023.115035 -
Journal of Translational Medicine Nov 2023Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this...
BACKGROUND
Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC.
METHODS
We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC.
RESULTS
In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi.
CONCLUSION
For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.
Topics: Humans; Stomach Neoplasms; Tongue; Saccharomyces cerevisiae; Microbiota; Bacteria; Saliva
PubMed: 37980457
DOI: 10.1186/s12967-023-04599-1 -
Cancer Biology & Therapy Dec 2023Oral tongue cancer is an extremely malignant tumor with high rate of lymphatic metastasis. Little is known about its invasion and metastasis mechanisms so far.
BACKGROUND
Oral tongue cancer is an extremely malignant tumor with high rate of lymphatic metastasis. Little is known about its invasion and metastasis mechanisms so far.
METHODS
To clarify the main role of CCL2 in tongue cancer progression, we performed Transwell migration assay to confirm the effects of different concentrations of CCL2 on the migration and invasion of tongue cancer cells. Next, by siRNA interference of RhoA and Rac1 in LNMTca8113 cells, we are able to observe that these two molecules block the effect of CCL2 on cell migration and cytoskeleton reorganization by laser confocal microscopy. Moreover, the AKT phosphorylation level of PI3K downstream molecule under the action of CCL2 also be detected by qRT-PCR and western blot, so as to determine whether CCL2 affects the proliferation of LNMTca8113 cells through PI3K/AKT pathway. Finally, we analyzed the relationship between plasma CCL2 level and various clinicopathological parameters in patients with tongue cancer. Results: We found that tongue cancer cells treated with CCL2 migrate faster at first. CCL2 may enhance the invasion and migration of LNMTca8113 cells by activating RhoA and Rac1 to promote cytoskeleton reorganization. Promotion of LNMTca8113 migration induced by CCL2 was inhibited by silence of RhoA and Rac1. CCL2 could increase the phosphorylation of downstream Akt/PI3K signal and promoted the proliferation. Plasma concentration confirmed that the CCL2 level was closely related to the clinical stage of tongue cancer. Patients with lower CCL2 levels had a relatively longer progression-free survival and total survival time.
RESULTS
After adding CCL2, the number of proliferation and migration of tongue cancer cells increased and the expression of RhoA and Rac1 rose up in LNMTca8113 cell line. The cytoskeleton reorganization was notable. Patients with higher serum levels of CCL2 had shorter progression-free survival than those with lower levels of CCL2 (P < 0.0001).
CONCLUSIONS
CCL2 promotes the invasion and metastasis of tongue cancer by PI3K/Akt pathway. The plasma level of CCL2 may predict prognosis of tongue cancer patients. CCL2 can serve as a potential therapeutic target for tongue cancer treatment.
Topics: Humans; Proto-Oncogene Proteins c-akt; Tongue Neoplasms; Signal Transduction; Lymphatic Metastasis; Phosphatidylinositol 3-Kinases; Cell Line, Tumor; Cell Proliferation; Prognosis; rhoA GTP-Binding Protein; rac1 GTP-Binding Protein; Chemokine CCL2
PubMed: 37132640
DOI: 10.1080/15384047.2023.2205342 -
Clinical Cancer Research : An Official... Jul 2023Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive...
PURPOSE
Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND.
EXPERIMENTAL DESIGN
To investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment.
RESULTS
Disease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977.
CONCLUSIONS
High ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC. See related commentary by Hondermarck and Jiang, p. 2342.
Topics: Humans; Animals; Mice; Artificial Intelligence; Reproducibility of Results; Neoplasm Invasiveness; Mouth Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37039710
DOI: 10.1158/1078-0432.CCR-22-3496 -
Frontiers in Immunology 2024The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well....
INTRODUCTION
The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined.
METHODS
We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively.
RESULTS
MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells , in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice.
CONCLUSION
The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.
Topics: Humans; Animals; Mice; Carcinoma, Squamous Cell; Tongue Neoplasms; Killer Cells, Natural; Cell Line; Tongue; Mucin-1
PubMed: 38390321
DOI: 10.3389/fimmu.2024.1337557 -
MBio Jun 2023The association between Candida albicans (C. albicans) and oral cancer (OC) has been noticed for a long time, but the mechanisms for C. albicans promoting OC are rarely...
The association between Candida albicans (C. albicans) and oral cancer (OC) has been noticed for a long time, but the mechanisms for C. albicans promoting OC are rarely explored. In this study, we determined that C. albicans infection promoted OC incidence in a 4-nitroquinoline 1-oxide (4NQO)-induced mouse tongue carcinogenesis model as well as promoted OC progression in a tongue tumor-bearing mouse model (C3H/HeN-SCC VII). We then demonstrated that tumor-associated macrophage (TAMs) infiltration was elevated during C. albicans infection. Meanwhile, the attracted TAMs polarized into M2-like macrophages with high expression of programmed death ligand 1 (PD-L1) and galectin-9 (GAL-9). Further analysis suggested that the interleukin (IL)-17A/IL-17RA pathway activated in OC cells was a contributor to the excessive TAMs infiltration in C. albicans-infected mice. Thus, we constructed IL-17A neutralization and macrophage depletion experiments in C3H/HeN-SCC VII mice to explore the role of IL-17A/IL-17RA and TAMs in OC development caused by C. albicans infection. The results showed that both IL-17A neutralization and macrophage depletion tended to reduce the TAMs number and tumor size in mice with C. albicans infection. Collectively, our finding revealed that C. albicans promoted OC development via the IL-17A/IL-17RA-macrophage axis, opening perspectives for revealing C. albicans-tumor immune microenvironment links. The relationship between fungi and cancer is gradually receiving attention. Among them, some clinical evidence has shown that may be a contributor to gastrointestinal cancers, especially oral cancer. However, the underlying mechanisms for promoting oral cancer need to be explored. For this reason, this study demonstrated the role of C. albicans in oral cancer development. Moreover, this study revealed the underlying mechanisms for C. albicans promoting oral cancer from the perspective of the tumor immune microenvironment.
Topics: Animals; Mice; Candida albicans; Candidiasis; Interleukin-17; Macrophages; Mice, Inbred C3H; Mouth Neoplasms; Tumor Microenvironment
PubMed: 37067414
DOI: 10.1128/mbio.00447-23 -
Scientific Reports Aug 2023Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been...
Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human interleukin (IL)-1β in the oral, esophageal and forestomach squamous epithelia feature chronic inflammation and a stepwise development of Barrett's esophagus-like metaplasia, dysplasia and adenocarcinoma at the squamo-columnar junction. However, the functional consequences of IL-1β-mediated chronic inflammation in the oral and esophageal squamous epithelia remain elusive. We report for the first time that in addition to the previously described Barrett's esophagus-like metaplasia, the L2-IL-1β mice also develop squamous epithelial dysplasia with progression to squamous cell carcinoma (SCC) in the esophagus and the tongue. L2-IL-1β showed age-dependent progression of squamous dysplasia to SCC with approximately 40% (n = 49) and 23.5% (n = 17) incidence rates for esophageal and tongue invasive SCC respectively, by 12-15 months of age. Interestingly, SCC development and progression in L2-IL-1β was similar in both Germ Free (GF) and Specific Pathogen Free (SPF) conditions. Immunohistochemistry revealed a T cell predominant inflammatory profile with enhanced expression of Ki67, Sox2 and the DNA double-strand break marker, γ-H2AX, in the dysplastic squamous epithelia of L2-IL-1β mice. Pro-inflammatory cytokines, immunomodulatory players, chemoattractants for inflammatory cells (T cells, neutrophils, eosinophils, and macrophages) and oxidative damage marker, iNOS, were significantly increased in the esophageal and tongue tissues of L2-IL-1β mice. Our recent findings have expanded the translational utility of the IL-1β mouse model to aid in further characterization of the key pathways of inflammation driven BE and EAC as well as ESCC and Oral SCC.
Topics: Animals; Child, Preschool; Humans; Mice; Adenocarcinoma; Barrett Esophagus; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Head and Neck Neoplasms; Inflammation; Metaplasia; Mice, Transgenic; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 37543673
DOI: 10.1038/s41598-023-39907-8