Torsten Eugen Reichert

Oral squamous cell carcinoma (OSCC) remains a major cause of cancer-related mortality worldwide, with limited biomarker-driven tools for risk stratification. CD147 is a membrane glycoprotein implicated in tumor metabolism, invasion, immune evasion, and therapy resistance. This study aimed to evaluate the prognostic and predictive relevance of CD147 expression in distinct tumor compartments of OSCC. Formalin-fixed tumor samples from 229 OSCC patients were analyzed via tissue microarray and immunohistochemistry to assess CD147 expression in the tumor center, periphery, and adjacent mucosa. Associations with clinicopathological parameters, survival, and therapy response were evaluated using non-parametric statistical tests, Kaplan–Meier, multivariate Cox, and binary logistic regression analyses. Complementary transcriptomic and immunological analyses were performed using The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis (UALCAN), Tumor and Immune System Interaction Database (TISIDB), and the Genotype-Tissue Expression (GTEx) project’s datasets. Low CD147 expression in the tumor invasive front was independently associated with improved overall survival, while expression in the tumor center or mucosa showed no prognostic value. No significant associations between CD147 and adjuvant therapy response were identified. TCGA-based analyses confirmed CD147 overexpression in tumors and its correlation with immunosuppressive signaling and resistance-associated transcriptional networks. Peripheral CD147 expression serves as a compartment-specific, independent prognostic marker in OSCC in this retrospective single-center cohort. Its spatially restricted prognostic relevance and association with immune modulation and therapy resistance highlight CD147 as a promising candidate for future biomarker-driven and therapeutic strategies.

Background: The anti-neoplastic activity of metformin is a subject of current debate. Preclinical data have suggested that metformin enhances PD-L1 anti-tumor effects in various cancer entities by decreasing insulin levels and inducing energetic stress. However, its impact on PD-L1 expression remains unclear in a clinical setting. Therefore, we aim to investigate the impact of metformin treatment in type 2 diabetes mellitus (DM) patients on PD-L1 expression in patients with oral squamous cell carcinoma (OSCC). Methods: We performed a retrospective analysis of patients with DM and OSCC treated at our tertiary referral center over a period of 12 years. The tumor proportion score (TPS), immune cell score (IC), and combined positive score (CPS) were used to quantify PD-L1 expression. PD-L1 expression of patients receiving metformin was compared to a control group without metformin prescription. Results: A total of 68 patients diagnosed with OSCC and DM were analyzed, with 24 receiving and 44 not receiving metformin therapy. No statistically significant differences were identified between the metformin and non-metformin groups for any of the scores (TPS: p = 0.818; IC: p = 0.748; CPS: p = 0.387). Conclusions: In contrast to previous studies, we could not find significant differences in PD-L1 expression between patients with and without metformin intake. Further research needs to shed light on the exact mechanism of metformin in different tumor entities. A comprehensive understanding of metformin’s role in cancer therapy could provide valuable insights for potential use of metformin as an adjuvant treatment to immune checkpoint therapy.

Introduction: Hyperbaric oxygen (HBO2) therapy involves the inhalation of pure oxygen in a pressure chamber under increased ambient pressure. Recent research indicates that circulating small extracellular vesicles (sEVs) play important roles in human physiology and pathology. Therefore, the objective of this pilot study was to monitor the impact of HBO2 therapy on the levels of circulating sEVs in the serum of patients with necrotizing soft-tissue infections (NSTI), aseptic bone necrosis (ABN) or idiopathic sudden sensory neural hearing loss (ISSNHL).Material and methods: Serum-derived sEVs were isolated and quantified in 80 patients before and after HBO2 therapy applied for NSTI, ISSNHL and ABN patients as well as in normal controls who received neither HBO2 therapy nor steroids.Results: We observed a significant increase of circulating sEVs in patients with ISSNHL after HBO2 therapy (p < 0.05), as well as significantly elevated levels of sEVs after HBO2 therapy compared to patients with NSTI (p < 0.05) and ABN (p < 0.01).Conclusions: The increase in the levels of sEVs in ISSNHL may be evidence for both the intended reduction of inflammation as a result of steroid therapy and the inhibitory effect of oxidative stress induced by HBO2 therapy. Thus, sEVs released during HBO2 therapy might play an important biological role in mediating the response to therapy and might be a promising approach to gain further insights into the therapeutic efficacy of HBO2 therapy.

Body fluids of patients with head and neck squamous cell carcinoma (HNSCC) are enriched in exosomes that reflect properties of the tumor. The aim of this study was to determine whether purine metabolites are carried by exosomes and evaluate their role as potential contributors to tumor immune escape. The gene expression levels of the purine synthesis pathway were studied using the Cancer Genome Atlas (TCGA) Head and Neck Cancer database. Exosomes were isolated from supernatants of UMSCC47 cells and from the plasma of HNSCC patients (n = 26) or normal donors (NDs; n = 5) using size exclusion chromatography. Ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to assess levels of 19 purine metabolites carried by exosomes. In HNSCC tissues, expression levels of genes involved in the purinergic pathway were upregulated indicating an accelerated purine metabolism compared to normal tissues. Exosomes from supernatants of UMSCC47 cells contained several purine metabolites, predominantly adenosine and inosine. Purine metabolite levels were enriched in exosomes isolated from the plasma of HNSCC patients compared to those isolated from NDs and carried elevated levels of adenosine (p = 0.0223). Exosomes of patients with early-stage disease and no lymph node metastasis contained significantly elevated levels of adenosine and 5′-GMP (p = 0.0247 and p = 0.0229, respectively). The purine metabolite levels in exosomes decreased in patients with advanced cancer and nodal involvement. This report provides the first evidence that HNSCC cells shuttle purine metabolites in exosomes, with immunosuppressive adenosine being the most prominent purine. Changes in the content and levels of purine metabolites in circulating exosomes reflect disease progression in HNSCC patients.

Dental follicle cells (DFCs) are dental stem cells and interesting options for regenerative therapies in dentistry. However, DFCs acquire replicative senescence in long-term cultures, but little is known about molecular processes. In previous studies, we observed that DFC cell lines become senescent at different rates. We hypothesized that short telomere length and increased DNA damage with genomic instability correlate with the accelerated induction of cellular senescence. For this study we compared DFC cell lines that became senescent at different rates (DFC_F: strong senescent phenotype; DFC_S: weak senescent phenotype). The telomeres of DFC_F were shorter than those of the telomeres of DFC_S prior senescence. Interestingly, telomere lengths of both cell lines were nearly unchanged after induction of senescence. Gene expression analyses with genes associated with DNA damage before and after the induction of cellular senescence revealed that almost all genes in DFCs_F were down-regulated while the gene expression in DFC_S was almost constitutive. Moreover, number of aneuploid DFC_F were significantly higher after induction of cellular senescence. Our results supported our initial hypothesis that telomere length and genomic instability correlate with the accelerated induction of cellular senescence in DFC_F.

The incidence of postoperative complications after head and neck surgery is high. This study evaluated the influence of early elective tracheostomy on the incidence of postoperative pneumonia and delirium. We reviewed the data of all patients who had undergone removal of an oropharyngeal tumor and microsurgical tissue transfer at our department in a two year period. Pearson’s Chi-squared test and the Fischer’s exact t-test were then used to measure the influence of patients’ preexisting conditions and risk factors and of early elective tracheostomy on the incidence of postoperative complications. In total, 47 cases were analyzed. Patients with an endotracheal tube were ventilated for a longer time (3.4 days vs. 1.5 days) and were transferred to the regular ward later (after 6.9 days vs. 4.7 days) than patients with tracheostomy. Only 1 (2.1%) of the patients with a tracheostomy developed pneumonia in contrast to 5 intubated patients (10.6%) and only 2 patients with a tracheostomy developed postoperative delirium (9.5%) in contrast to 8 intubated patients (30.8%). Early primary tracheostomy in patients undergoing resection of oropharyngeal cancer seems to have numerous benefits, such as lower complication rates with regard to pneumonia and postoperative delirium and shorter duration of both mechanical ventilation and intensive care unit (ICU) stays. Further studies have to evaluate if these benefits also influence morbidity and mortality rates.

This article offers a short review of risk factors, oral precancerous conditions, and oral precancerous lesions which may cause oral squamous carcinoma. Current diagnostic methods and multidisciplinary strategies for the early detection and appropriate therapy of oral squamous carcinomas are discussed. Close cooperation of oral and maxillofacial surgeons, head and neck surgeons, radiotherapists, and oncologists is essential for the effective therapy of oral squamous carcinomas.