Tongue Squamous Cell Carcinoma Research Articles

Cryoprotective Ice-Philic Black Phosphorus Nanosheets for Augmented Thawing of Frozen Cells.

Controlling ice formation is critical in fields such as atmospheric science and biological cryopreservation. However, thermal heterogeneity during freezing and thawing in cryopreservation causes uneven ice crystallization and melting, leading to mechanical and thermal stress-induced damage. This study introduces biocompatible and biodegradable black phosphorus (BP)-polyethylene glycol-amine nanosheets (NS) to address this issue. BP NS primarily localize at ice grain boundaries, while amine groups of NH2-PEG-NH2 form hydrogen bonds with H2O molecules, penetrating ice crystals. In situ cross-sectional observations confirmed that BP-PEG-NH2 NS promotes uniform melting and facilitates ice cracks and boundaries. Heat transfer analysis using a bidirectional heating system revealed that the internal heat energy varies based on BP dispersion within the ice crystals. When applied to the cryopreservation of human tongue squamous cell carcinoma cells, BP-PEG-NH2 NSs significantly improved post-thaw viability. It presents a promising strategy for designing thawing materials after cryopreservation of cells, tissues, and organs.

Y27632 induces tongue squamous cell carcinoma cell apoptosis through MAPK-ERK/JNK signal

Abstract Objectives ROCK signaling is considered a therapeutic target for oral squamous cell carcinoma (OSCC). Y27632, a well-established ROCK inhibitor, has previously been reported to block oral squamous cell carcinoma cell growth and has shown cell type dependence in the treatment of other cancers. TP53 is one of the most frequently mutated genes in head and neck cancer. Here, we aim to investigate the role of Y27632 in wild-type and p53 mutant (R175H) SCC9 cells. Methods The p53-mutation (R175H) and p53-null SCC9 cell line were conducted, then, CCK8, colony formation, wound-healing assays, and transwell assay were employed to investigate the role of Y27632 in wtp53 and mutp53 SCC9 cells. The effects of Y27632 in SCC9 cells were also confirmed by the knockdown of ROCK1/2. Additionally, cell cycle and apoptosis were assessed using flow and western blot analysis. The impact of Y27632 on cell senescence was confirmed through the senescence-associated β-gal staining. Furthermore, the inhibition of Y27632 was examined in vivo using tumor-bearing nude mice. Results Our study demonstrates that Y27632 effectively impeded the proliferation of tongue squamous cell carcinoma (TSCC) cells in vitro and in vivo. Additionally, the proliferation and migration of wtp53 and mutp53 SCC9 cells were also significantly suppressed by Y27632 or ROCK siRNA in vitro. Mechanistically, Y27632 induced apoptosis in SCC9 cells via the MAPK-ERK/JNK signaling pathway. Conclusions Our data demonstrated that Y27632 induces apoptosis in SCC9 cells via the MAPK-ERK/JNK signaling pathway, regardless of the presence of p53 mutant variants (R175H). This will provide a potential therapeutic drug for TSCC treatment in the future.

Depth of invasion and extranodal extension: the influential factors to predict survival rate of patients with oral tongue squamous cell carcinoma

BackgroundCancer staging is essential in determining patients’ prognoses and designing the appropriate treatment strategy. American Joint Committee on Cancer has released the latest version of the staging system for tongue SCC. However, it is interesting to know whether this change in staging and the addition of depth of invasion (DOI) and the extra-nodal extension (ENE) have any influence on patients’ prognosis.MethodsIn this retrospective cohort study, the pathology records of patients with tongue SCC who underwent surgery at the Pathology Department of Cancer Institute Hospital, 2017–2021, were collected by referring to the hospital information system. Then the rate of change of pT, pN, and overall stage were assessed based on American Joint Committee on Cancer 7th and 8th editions.ResultsThe records of 204 patients were included in the final analysis. Significant changes in the staging system 2021 resulted in upstaging 64 patients (31.4%) in the overall stage, 91 patients (44.6%) in pT, and 30 patients (14.7%) in pN. The survival of upstaged patients was inferior compared to those without upstaging. However, this was not statistically significant for tumor and overall upstaging in the univariate analysis, while those with upstaged pN had significantly shorter survival. In the multivariate analysis, pT upstage also significantly impacted survival.ConclusionThis study showed the importance of pathology reports based on the latest edition of the American Joint Committee on Cancer, the accuracy in examining factors such as depth of invasion and extra-nodal extension.

Treatment strategy for cervical lymph node metastases from early-stage tongue and floor of the mouth squamous cell carcinoma using tumour budding and depth of invasion as predictors.

This study aimed to determine whether elective neck dissection can help improve outcomes in early-stage tongue and floor squamous cell carcinoma (SCC) by statistically analysing the relationship between information obtained from biopsy specimens and the incidence and prognosis of cervical lymph node metastasis (CLM). Biopsy specimens of 103 patients diagnosed with early cT1-T2 cancer of the tongue and floor of the mouth were included. Multivariate analysis showed that the three parameters significantly correlated with CLM, and univariate analyses showed that budding score (BS) ≥ 5 and pathological depth of invasion (pDOI) ≥ 5mm were independent risk factors for CLM. There were significant differences in the 5-year cumulative disease-specific survival between the BS < 5 and BS ≥ 5 groups, the pDOI < 5mm and pDOI ≥ 5mm groups, and the positive and negative budding and depth of invasion (BD) score groups. In early-stage tongue and floor of the mouth cancers with maximum tumour diameter ≤ 20mm, it may be necessary to treat occult CLM during initial surgery based on the following preoperative criteria: pDOI ≥ 5mm or BS ≥ 5 in biopsy specimens and DOI ≥ 8mm on imaging. The BD model exhibited the highest specificity and proved helpful for CLM prediction. pDOI ≥ 5mm and BS ≥ 5 were independent predictors of CLM and prognosis in early-stage tongue and floor of the mouth cancers with a maximum tumour diameter of 20mm.

Intraoperative rapid assessment of the deep muscle surgical margin of tongue squamous cell carcinoma via Raman spectroscopy.

An accurate assessment of the surgical margins of tongue squamous cell carcinoma (TSCC), especially the deep muscle tissue, can help completely remove the cancer cells and thus minimize the risk of recurrence. This study aimed to develop a classification model that classifies TSCC and normal tissues in order to aid in the rapid and accurate intraoperative assessment of TSCC surgical deep muscle tissue margins. The study obtained 240 Raman spectra from 60 sections (30 TSCC and 30 normal) from 15 patients diagnosed with TSCC. The classification model based on the analysis of Raman spectral data was developed, utilizing principal component analysis (PCA) and linear discriminant analysis (LDA) for the diagnosis and classification of TSCC. The leave-one-out cross-validation was employed to estimate and evaluate the prediction performance model. This approach effectively classified TSCC tissue and normal muscle tissue, achieving an accuracy of exceeding 90%. The Raman analysis showed that TSCC tissues contained significantly higher levels of proteins, lipids, and nucleic acids compared to the adjacent normal tissues. In addition, we have also explored the potential of Raman spectroscopy in classifying different histological grades of TSCC. The PCA-LDA tissue classification model based on Raman spectroscopy exhibited good accuracy, which could aid in identifying tumor-free margins during surgical interventions and present a promising avenue for the development of rapid and accurate intraoperative techniques.

8270 A Rare Case Of PTHrP Induced Severe Hypercalcemia Secondary To Squamous Cell Carcinoma Of Tongue

Abstract Disclosure: N. Vennelaganti: None. S. Vennelaganti: None. K. McCowen: None. Background: PTHrP-mediated hypercalcemia is often associated with solid organ malignancies and indicates a poor prognosis. The occurrence of this condition due to SCC of the head and neck, particularly of the tongue, is uncommon. This case report aims to shed light on this rare clinical presentation. Clinical Case: A 70-year-old woman with a history of tobacco use disorder, alcoholic liver cirrhosis, and a chronic fungal prosthetic joint infection presented with altered mental status and acute kidney injury. Laboratory tests revealed a corrected calcium level of 15.4 mg/dL and suppressed PTH of 3 pg/mL, indicating non-PTH-dependent hypercalcemia. Differentials considered included malignancy, multiple myeloma, 1,25 OH Vit D mediated hypercalcemia via fungal granuloma formation, and immobilization. Diagnostic evaluation revealed normal levels of 25 hydroxy Vitamin D ie: 54 ng/mL, normal kappa to lambda ratio suggestive of negative myeloma screen, normal TSH of 2.81 uIU/mL, and a low 1,25 OH Vit D level ie: 11.4 pg/mL (Ref range: 19.9-79.3 pg/mL). An elevated PTHrP concentration of 9.7 pmol/L (ref range 0-3.4 pmol/L) was noted. CT angiography performed for stroke evaluation incidentally discovered a base of tongue mass, which was difficult to appreciate on exam due to obtundation. A biopsy confirmed SCC of the tongue, and she was determined to be Stage IVA. The patient's hypercalcemia was determined to be secondary to PTHrP production from the tongue SCC compounded by immobilization. She was treated with IV fluids and subcutaneous calcitonin, normalizing her calcium levels over 20 days. IV Bisphosphonates were held inpatient due to poor renal function. She was seen by oncology and determined to not be fit for surgical management or chemotherapy. Radiation therapy was advised for management and patient was discharged. While awaiting her outpatient radiation treatment, the patient had another episode of altered mental status and was found to have a serum calcium of 16.4 mg/dL. She was managed with IV fluids, calcitonin and IV Zoledronate which improved her serum calcium. She has since been receiving monthly IV Zometa with oncology for hypercalcemia of malignancy. She was recently readmitted with severe oropharyngeal and pharyngeal dysphagia and has received a PEG tube for feeding. She is still pending radiation therapy for SCC tongue. Conclusion: Initially, during the workup of this case, we believed her hypercalcemia was likely immobilization-induced, but thorough investigation and the elevated PTHrP levels steered us towards malignancy as a potential etiology. This case is an example of an occult malignancy which lead to severe hypercalcemia. It also contributes to the understanding of hypercalcemia in cancer patients and highlights the rare association of SCC of the tongue with PTHrP-mediated hypercalcemia . PTHrP secreting SCC of head and neck are typically associated with a poor prognosis. Presentation: 6/2/2024

Antibacterial profile and antiproliferative activities over human tumor cells of new silver(I) complexes containing two distinct trifluoromethyl uracil isomers

New silver(I) complexes of 5-(trifluoromethyl)uracil (5TFMU) and 6-(trifluoromethyl)uracil (6TFMU) isomers were synthesized, characterized, and evaluated as antibacterial and antiproliferative agents. Based on elemental and thermogravimetric analyses, the Ag-5TFMU and Ag-6TFMU species are formulated as AgC5H2F3N2O2 and Ag2C5HF3N2O2, respectively. Infrared and 13C solid-state nuclear magnetic resonance spectroscopies suggest coordination of the trifluoromethyluracil isomers to silver by both nitrogen and oxygen atoms. Confirmation of their structure and connectivity was achieved, in the absence of single crystals of suitable quality, by state-of-the-art structural powder diffraction methods. In Ag-5TFMU, the organic ligand is tridentate and two distinct metal coordination environments are found (linear AgN2 as well as C2v AgO4 geometries), whereas Ag-6TFMU contains a complex polymeric structure with tetradentate dianionic 6TFMU moieties and five distinct AgX2 (X = N, O) fragments, further stabilized by ancillary (longer) Ag…O contacts. These species presented modest activity over Gram-positive and Gram-negative bacterial strains, whereas Ag-6TFMU was active over a set of tumor cells, with the best activity over prostate (PC-3) and kidney cell lines and selectivity indices of 4.6 and 1.3, respectively. On the other hand, Ag-5TFMU was active over all considered tumor cells except MCF-7 (breast cancer). The best activity was found for PC-3 cells, but no selectivity was observed. The Ag-5TFMU and Ag-6TFMU species also reduced the proliferation of tongue squamous cell carcinoma cell lines SCC − 4 and SCC-15. Preliminary biophysical assays by circular dichroism suggest that the Ag-5TFMU complex interacts with DNA by intercalation, an effect not seen in Ag-6TFMU.

A study on direct metastasis to levels III, IV in oral tongue squamous cell carcinoma

ObjectiveThis study aimed to determine the frequency and specific metastatic patterns of direct metastasis to levels III and IV in oral tongue squamous cell carcinoma (OTSCC) among Japanese individuals. MethodsWe conducted neck dissections on 319 patients at our department from January 2001 to December 2020. Of these, 220 patients with histopathological evidence of lymph node metastasis were included in the study. Lymph node metastases were categorized by level to elucidate the metastatic patterns. Additionally, metastatic sites within level III were identified as either anterior or posterior to the internal jugular vein, and these findings were compared between the direct metastatic group and the non-direct metastatic group. ResultsAmong the patients, 13 experienced direct metastases to level III or IV. Specifically, 12 patients had metastases at level III, and one patient had metastases at both levels III and IV, constituting 5.9% (13/220) of those with cervical lymph node metastasis in OTSCC. No patients exhibited direct metastases solely to level IV. Within level III, the direct metastasis group showed a significantly higher incidence of metastasis anterior to the internal jugular vein (p = 0.03). ConclusionsDirect metastasis to levels III and/or IV occurred in 5.9% of the cases. Although elective neck dissection up to level III is generally sufficient, metastasis to level IV, while infrequent, can occur. Therefore, vigilant follow-up with attention to the lower neck regions is crucial.

Initial negative resection margin versus revised negative resection margin in patients who underwent surgery without adjuvant therapy for early-stage oral tongue squamous cell carcinoma

BackgroundIn cases of positive resection margin (RM), re-resection is generally recommended. There has been controversy about the oncologic impact of revised negative RMs after re-resection. The aim of this study was to investigate the oncologic impact of revised negative RM in patients who underwent surgery without adjuvant therapy for early-stage (pT1-2/N0) oral tongue squamous cell carcinoma (OSCC). MethodsWe retrospectively analyzed patients with pT1-2 N0 OSCC who did not receive adjuvant therapy (N=441). These patients were classified into an initial negative RM (R0, n = 380) group and a revised negative RM (R1-R0, n = 61) group. Demographic and clinical data (T stage, tumor length, depth of invasion [DOI], lymphovascular invasion [LVI], perineural invasion [PNI], and recurrence) were compared between the R0 and R1-R0 groups. ResultsAge, sex, T stage, DOI, LVI, PNI, and SUVmax were not significantly different between the two groups. Local recurrence was more frequent (P=0.045) in the R1-R0 group (13.1 %) than in the R0 group (5.5 %). Local recurrence-free survival was better in the R0 group than in the R1-R0 group (P=0.046). There was no significant difference in overall recurrence or overall survival. On multivariate analysis, initial positive RM was the independent significant risk factor (hazard ratio, 2.249; 95 % confidence interval, 1.025–4.935; P=0.043) for local recurrence. ConclusionA revised clear RM after initial cut-through margin is a risk factor for local recurrence in early-stage OSCC. Cautious should be considered in early-stage OSCC patients with revised clear RM.

Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model.

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.

Metastatic tongue squamous cell carcinoma at a percutaneous endoscopic gastrostomy site via introducer technique

AbstractBackgroundPercutaneous endoscopic gastrostomy (PEG) site metastases from head and neck cancers have been reported many times using the pull technique, in which a catheter passes through the oral cavity and pharynx.Case presentationA 69‐year‐old man with recurrent tongue squamous cell carcinoma underwent PEG placement using the introducer technique before chemoradiotherapy. After 6 months, the patient developed a metastasis of tongue carcinoma at the PEG site.ConclusionThe risk of PEG site metastasis is not eliminated even with the introducer technique, which is not in direct contact with the tumor.

Identification and Validation of an Invasion-Related Disease-Free Survival Prognostic Model for Tongue Squamous Cell Carcinoma

Introduction: Tongue squamous cell carcinoma (TSCC) is a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients. Methods: We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Results: A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line. Conclusion: This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.

Mitochondria-Targeting AIEgens as Pyroptosis Inducers for Boosting Type-I Photodynamic Therapy of Tongue Squamous Cell Carcinoma.

The development of a photosensitizer (PS) that induces pyroptosis could be a star for photodynamic therapy (PDT), particularly with type-I PSs that produce reactive oxygen species (ROS) in a hypoxic tumor microenvironment. Since pyroptosis is a recently characterized cell death pathway, it holds promise for advancing PDT in oncology, with PSs playing a critical role. Herein, we develop a PS named Th-M with aggregation-induced emission (AIE) characteristics for type-I PDT against tongue squamous cell carcinoma (TSCC). Th-M stands out for its exceptional mitochondrial-targeting ability, which triggers mitochondrial dysfunction and leads to Caspase-3 and Gasdermin E (GSDME) cleavage under white light irradiation, inducing pyroptosis in TSCC cells. Our studies verify the effectiveness of Th-M in destroying cancer cells in vitro and suppressing tumor growth in vivo while also demonstrating a favorable biosafety profile. This work pioneers the application of Th-M as a mitochondria-targeted, type-I PS that leverages the mechanism of pyroptosis, offering a potent approach for the treatment of TSSC with promising implications for future PDT of cancers.

A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFβ2 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/TGFβ2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFβ2 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/TGFβ2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.

The study on 4D culture system of squamous cell carcinoma of tongue

Traditional cell culture methods often fail to accurately replicate the intricate microenvironments crucial for studying specific cell growth patterns. In our study, we developed a 4D cell culture model-a precision instrument comprising an electromagnet, a force transducer, and a cantilever bracket. The experimental setup involves placing a Petri dish above the electromagnet, where gel beads encapsulating magnetic nanoparticles and tongue cancer cells are positioned. In this model, a magnetic force is generated on the magnetic nanoparticles in the culture medium to drive the gel to move and deform when the magnet is energized, thereby exerting an external force on the cells. This setup can mimic the microenvironment of tongue squamous cell carcinoma CAL-27 cells under mechanical stress induced by tongue movements. Electron microscopy and rheological analysis were performed on the hydrogels to confirm the porosity of alginate and its favorable viscoelastic properties. Additionally, Calcein-AM/PI staining was conducted to verify the biosafety of the hydrogel culture system. It mimics the microenvironment where tongue squamous cell carcinoma CAL-27 cells are stimulated by mechanical stress during tongue movement. Electron microscopy and rheological analysis experiments were conducted on hydrogels to assess the porosity of alginate and its viscoelastic properties. Calcein-AM/PI staining was performed to evaluate the biosafety of the hydrogel culture system. We confirmed that the proliferation of CAL-27 tongue squamous cells significantly increased with increased matrix stiffness after 5 d as assessed by MTT. After 15 d of incubation, the tumor spheroid diameter of the 1%-4D group was larger than that of the hydrogel-only culture. The Transwell assay demonstrated that mechanical stress stimulation and increased matrix stiffness could enhance cell aggressiveness. Flow cytometry experiments revealed a decrease in the number of cells in the resting or growth phase (G0/G1 phase), coupled with an increase in the proportion of cells in the preparation-for-division phase (G2/M phase). RT-PCR confirmed decreased expression levels of P53 and integrinβ3 RNA in the 1%-4D group after 21 d of 4D culture, alongside significant increases in the expression levels of Kindlin-2 and integrinαv. Immunofluorescence assays confirmed that 4D culture enhances tissue oxygenation and diminishes nuclear aggregation of HIF-1α. This device mimics the microenvironment of tongue cancer cells under mechanical force and increased matrix hardness during tongue movement, faithfully reproducing cell growthin vivo, and offering a solid foundation for further research on the pathogenic matrix of tongue cancer and drug treatments.

Contralateral submental artery island flap for oral tongue reconstruction — a retrospective study in patients with oral tongue squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related death in developing countries. The oral tongue is the most common site involved by OSCC. About a third of the patients have neck nodal metastasis at presentation. Reconstruction of the oral tongue after resection for cancer is necessary for proper rehabilitation. For patients who are medically unfit for prolonged surgery like a free tissue transfer, local flaps are employed for tongue reconstruction. The submental flap is a popular option. However, when there is extensive floor of mouth involvement or bulky nodal disease in ipsilateral level 1, harvesting the submental flap based on contralateral facial vessels is possible, without compromising oncological safety. We discuss the feasibility and outcomes of contralateral submental artery island flap for reconstruction after resection of oral tongue carcinoma in a retrospective series of 34 patients followed up for a median of 8.5 months. ResultsOf the 34 oral tongue cancer patients in the study, 16 had neoadjuvant chemotherapy prior to surgery. 33 underwent bilateral neck dissection. Two patients had partial flap loss which was managed conservatively. There were five patients who had either locoregional or distant recurrence, none in the flap site. Three had pathological positive nodes at contralateral level 1b and two had pathologically positive nodes in contralateral level 1b. Tongue motility and speech intelligibility were satisfactory on follow-up. ConclusionIn the properly selected patient, the contralateral submental artery island flap offers an oncologically safe and technically simpler alternative for free flap reconstruction.

Role of midline raphe in compartmental surgery for squamous cell carcinoma of the tongue.

In the present study, we investigated how tumor distance from midline (TDFM) and depth of invasion (DOI) may affect survival outcomes after compartmental tongue surgery (CTS) for oral tongue squamous cell carcinoma (OTSCC). A retrospective series of cT2-T3 OTSCC treated with upfront CTS at our Department from 2010 to 2021 was evaluated. Radiological and pathological DOI and TDFM were correlated. The main outcomes were overall (OS) and loco-regional recurrence free survival (LRRFS). The linear relationship between DOI and TDFM with 2-year OS and LRRFS was tested. Survival estimates were obtained by the Kaplan-Meier method. Univariate analysis was performed for variables of interest, and results expressed in terms of hazard ratios and 95% confidence intervals. A total of 64 patients underwent CTS and neck dissection. No significant difference was found between pathological (pDOI) and radiological DOI (rDOI) (p = 0.321) or between pathological (pTDFM) and radiological TDFM (p = 0.435). Two- and 5-year OS and LRRFS were 85.7% and 70.4%, 84.3% and 76.1%, respectively. A linear and significant relationship with OS (p = 0.020) and LRRFS (p = 0.013) was found for pDOI; although linear, the relationship between pTDFM was not statistically significant for either survival outcomes. Once categorized, the ideal cut-off for pDOI according to OS was set at 10mm (p = 0.023). In patients undergoing CTS for primary OTSCC, magnetic resonance-derived rDOI represents an accurate estimate of pDOI, In contrast, TDFM was not associated with OS suggesting that the median raphe is a safe deep margin for CTS. BS/231,009 retrospectively registered.

Risk factors and impact of occult and skip metastasis in early-stage oral tongue squamous cell carcinoma.

To investigate risk factors associated with occult lymph node metastases (ONM) and skip metastasis in early-stage oral tongue squamous cell carcinoma (OTSCC) patients. Meanwhile, to analyze the contribution of metastatic nodes to survival outcomes. 544 OTSCC patients who were clinically staged T1-T2N0 with pathologic results from May 2018 to January 2024 were enrolled. Those with ONM were divided into subgroups with or without skip metastasis. Clinical, laboratorial, radiological and pathological factors between groups were analyzed by using univariate analysis and multivariate logistic analysis. The association of tumor growth behavior with the metastatic pattern of lymph nodes was summarized. Additionally, disease free survival (DFS) among different groups were compared using Kaplan-Meier analysis. Tumor growth behavior was associated with ONM. Tumor thickness with a threshold of 6.4mm was not inferior to histological depth of invasion in predicting ONM. Only 1.3% of patients had nodal involvement of neck level IV or V. The DFS of patients with ONM were significantly reduced than those without ONM (P<0.001). The DFS between patients with and without skip metastasis exhibited no statistical significance(P = 0.246). The 1-year, 2-year recurrence rates of patients with or without ONM were 31.9%, 37.5%, 10.1% and 14.0%, correspondingly. Tumor thickness with a threshold of 6.4mm could be used as a preoperative predictor for ONM. Elective neck dissection of level I - III might be sufficient for early stage OTSCC patients. OTSCC patients with ONM should be closely observed during the first 2 years after surgery. The risk of ONM in early stage OTSCC patients might be predicted by tumor thickness calculated on MR imaging. Elective neck dissection of level I - III could remove micrometastases timely and effectively.

Tongue Squamous Cell Carcinoma Prognosis Can Be Effectively Predicted by LncRNA LIPH4: A Prospective Study.

LIPH4 has been identified as an oncogenic lncRNA in different malignant diseases. This research aims to elucidate the link between the expression of LIPH4 and its prognostic application in tongue squamous cell carcinoma (TSCC). To assess the expression of LIPH4, 142 TSCC and normal cases, respectively, which met the selection parameters, were used for qRT-PCR analysis. Furthermore, the association of LIPH4 expression with TSCC's clinicopathological features was identified via the Chi-square test. Moreover, the Kaplan-Meier test was used for calculating the survival rates, whereas the association of patient survival with prognostic factors was assessed with the help of Cox proportional hazard analysis. The data indicated upregulated LIPH4 levels in TSCC samples than healthy samples. Furthermore, LIPH4 expression was associated with TSCC differentiation and stage, where increased expression indicated reduced disease-free survival (DFS) and overall survival (OS) rates. Additionally, advanced TSCC individuals with enhanced LIPH4 expression had reduced OS and DFS rates than those with reduced LIPH4 expression. Serum LIPH4 could be a promising diagnostic bio-index for TSCC, with an area under the curve of 0.8920 (95% CI = 0.8540-0.9299). These data revealed that the overexpression of LIPH4 might be a substantial prognostic factor for independently predicting the OS and DFS rates of TSCC patients. Altogether, this research revealed that the expression of LIPH4 expression is closely associated with TSCC progression and, therefore, can be employed as a biomarker for its prognosis.

Antihypertensive agent losartan promotes tongue squamous cell carcinoma cell proliferation via EGFR/ERK1/2/cyclin D1 signaling axis

ObjectiveTo study the effects of losartan, an angiotensin II receptor blocker, in the SCC4 and SCC25 human tongue squamous cell carcinoma cell lines. MethodsCell proliferation was measured by MTS/PMS activity and trypan blue exclusion assays. The levels of the cell proliferation marker, cyclin D1, were analyzed by western blotting. Apoptosis was assessed by caspase-3 activation and Annexin V-FITC/propidium iodide double staining. Activation of epidermal growth factor receptor (EGFR) and ERK1/2 was validated by western blotting. ResultsModerate concentrations of losartan enhanced the proliferation of SCC4 and SCC25 cells. However, high losartan concentrations induced apoptosis in SCC4 cells. Losartan activated the EGFR/ERK1/2/cyclin D1 signaling axis, which in turn promoted cell proliferation. Afatinib (EGFR inhibitor) and U0126 (ERK1/2 inhibitor) abolished losartan-induced cell proliferation. In contrast, UC2288 (p21 inhibitor) enhanced it. ConclusionsLosartan exhibited dual effects on tongue squamous cell carcinoma cells. Moderate losartan concentrations facilitated cell proliferation, whereas high concentrations induced cytotoxicity in tongue carcinoma cells.