Department of Biochemistry

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer, driven by either Merkel cell polyomavirus (MCPyV) integration or ultraviolet (UV)-induced mutations. In MCPyV-positive tumors, viral T antigens inactivate tumor suppressors pRb and p53, while virus-negative MCCs harbor UV-induced mutations that activate similar oncogenic pathways. Key signaling cascades, including PI3K/AKT/mTOR and MAPK, support tumor proliferation, survival, and resistance to apoptosis. Histologically, MCC consists of small round blue cells with neuroendocrine features, high mitotic rate, and necrosis. The tumor microenvironment (TME) plays a central role in disease progression and immune escape. It comprises a mix of tumor-associated macrophages, regulatory and cytotoxic T cells, and elevated expression of immune checkpoint molecules such as PD-L1, contributing to an immunosuppressive niche. The extracellular matrix (ECM) within the TME is rich in proteoglycans, collagens, and matrix metalloproteinases (MMPs), facilitating tumor cell adhesion, invasion, and interaction with stromal and immune cells. ECM remodeling and integrin-mediated signaling further promote immune evasion and therapy resistance. Although immune checkpoint inhibitors targeting PD-1/PD-L1 have shown promise in treating MCC, resistance remains a major hurdle. Therapeutic strategies that concurrently target the TME—through inhibition of ECM components, MMPs, or integrin signaling—may enhance immune responses and improve clinical outcomes.

Objectives: Inflammatory fibroid polyps, also known as Vanek’s tumors, are rare benign lesions of the gastrointestinal tract. Although the exact cause remains unclear, several theories suggest an association with inflammatory processes and genetic factors. This study aims to present the largest cohort of inflammatory fibroid polyp cases to date, analyzing their clinical presentation, diagnostic methods, and treatment approaches. Materials and methods: A retrospective multicentric analysis was conducted on 67 patients diagnosed with inflammatory fibroid polyps between 2013 and 2023 across four hospitals. Clinical data regarding tumor location, size, symptoms, and treatment were collected. Non-parametric statistical tests, including the chi-square test, Cramér’s V coefficient, and the Mann–Whitney U test, were used to identify association between tumor characteristics, location, and treatment outcomes. Results: The cohort included 67 patients (58.2% female, median age 60 years). The stomach was the most common tumor site (47.8%), followed by the colon (32.8%), and small intestine (10.4%). The majority of patients (73.1%) were asymptomatic, while 9% experienced intestinal obstruction, all of which were located in the small intestine. Endoscopic resection was successful in 77.6% of cases, but surgical intervention was more frequently required for tumors in the small intestine. A significant association was found between larger tumor size, emergency presentation, intestinal location, and the need for surgery. Conclusions: Inflammatory fibroid polyps are commonly managed with endoscopic resection, particularly in gastric and colonic locations. However, small intestinal tumors more often need surgical treatment, especially when presenting with complications like intestinal obstruction.

Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often limited by side effects and drug resistance. Temozolomide is the most commonly used chemotherapy; however, resistance and lack of efficacy in recurrent GBM hinder its success. Tumor treating fields (TTFields), a novel non-invasive modality that utilizes alternating electric fields, have recently emerged as a promising treatment for GBM. TTFields work by disrupting the function of the mitotic spindle and inducing apoptosis in cancer cells. They can be especially effective when combined with other therapies. TTFields enhance drug delivery when paired with chemotherapy by increasing the permeability of the blood–brain barrier and cell membranes, leading to more effective tumor inhibition. Similarly, TTFields increase cancer cell sensitivity to radiation therapy and improve the efficacy of targeted therapies, such as sorafenib and immunotherapy, particularly in extra-cranial tumors. The Optune device, the primary medical device for TTFields’ delivery, offers a convenient and versatile treatment option, allowing remote care and exhibiting fewer adverse effects. This review discusses the potential of TTFields as a valuable addition to GBM treatment, particularly in combination therapies, and highlights the device’s clinical applications.

Background/Objectives: Osteosarcoma is an aggressive bone malignancy with high metastatic potential to the lungs. CTCs, as seeds of metastasis, play an important role in the spread of this cancer, and, therefore, their isolation, culture, and gene expression analysis promises valuable insights into the progression and metastatic cascade of osteosarcoma. The aim of this study was to isolate and culture CTCs from osteosarcoma-bearing mice and compare their migration, radioresistance, and gene expression with their parental cell line. Methods: CTCs from LM8-inoculated mice were isolated and cultured. The gene expression of the CTC-derived cell lines was then compared to the parental cell line. Furthermore, a Transwell assay, a clonogenic assay after irradiation, and immunohistochemical stainings were used to compare the CTC-derived cell lines with the parental cell line. Results: The CTC-derived cell lines differed significantly in gene expression from their parental cell line. 361 differentially expressed genes were identified, among which GO and KEGG analysis revealed major differences in the expression of genes related to antigen processing and presentation and extracellular matrix constituents. In addition, the CTC-derived cell lines were observed to have a higher migratory capacity and comparable radioresistance compared to the parental cell line. CD44 expression was found to be conserved in CTC-derived cell lines. Conclusions: This study provides a comparison between CTC-derived and their parental cell lines in terms of gene expression, migration, and radioresistance. Our findings allow for further research in the field of osteosarcoma CTCs and their generation. Furthermore, the identified DEGs between CTCs and their parental cell line can serve as a reference point for targeted therapies against osteosarcoma CTCs.