Purpose: Antibody therapy for chronic rhinosinusitis with nasal polyps (CRSwNP) has been established in Germany since 2019. With limited long-term data on biologic treatment for CRSwNP, we conducted a comprehensive evaluation of our 4-year data. This monocentric study aims to assess the real-world effects of this treatment on clinical course, quality of life, treatment adherence, biologic switching, dual therapy, and comorbidities. Methods: We retrospectively analysed biologic therapy data in patients with severe chronic rhinosinusitis with nasal polyps. 191 patients with CRSwNP treated with Dupilumab, Mepolizumab, or Omalizumab were observed for up to 4 years in a real-life setting. Results: We observed clear symptom improvements with few side effects. No loss of efficacy or tolerability was noted during the 4-year period. Patients reported high satisfaction compared to previous therapies, with overall improved quality of life. Revision surgery or oral steroid use during biologic therapy was rare. Some patients prolonged injection intervals or discontinued steroid nasal spray. Biologic switching occurred infrequently due to side effects or inadequate response and was generally well tolerated. Many patients reported additional positive effects such as asthma or allergy symptom improvement and reduced medication intake. Conclusion: In summary, this study confirms the potency and tolerability of biologics for CRSwNP treatment, with sustained efficacy over 4 years. Biologic switching is a viable option for inadequate response or intolerable side effects. Therapy positively impacts Th2 comorbidities, corticosteroid requirements, surgery need, and overall compliance remains high. Clinical trial registration: Project No.: 22–0802. Registry name: Biologika bei Patient*innen mit chronischer Sinusitis mit Nasenpolypen.
We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.
Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues.