Anna Grenda

Background: Currently, increasing attention is being paid to the role of genes other than CFTR and their variants as factors modifying the course of cystic fibrosis (CF). One such gene is SLC26A9, which encodes a protein involved in chloride and bicarbonate transport across the epithelial cell membrane. Variants of SLC26A9, such as c.229G>A (p.Gly77Ser) and c.1885C>T (p.Pro629Ser), have been described in patients with severe and rapidly progressive CF. The aim of this study was to identify SLC26A9 variants in a group of 20 patients with CF. Methods: DNA was isolated from blood samples and collected from all patients. Fragments of exons 3 and 17 of the SLC26A9 gene were amplified by PCR and sequenced using the Sanger method. Results: An SLC26A9 variant was identified in two siblings. These patients were diagnosed with CF in adulthood and presented with moderate pulmonary symptoms without exocrine pancreatic insufficiency. In both siblings carrying the CFTR variants p.Phe508del and c.3140-26A>G, the SLC26A9 variant c.1847C>T (p.Pro616Leu) was detected. This variant has not been widely described in the literature and has not previously been associated with CF. Conclusions: The c.1847C>T (p.Pro616Leu) variant is located near a domain that may affect the transport function of the SLC26A9 protein. However, patients in whom the variant was identified did not present a severe disease phenotype. Further studies on larger patient cohorts are required, and at present this variant should be considered of uncertain significance in CF.

Objectives: Early-stage non-small cell lung cancer (NSCLC) may represent a period during which interactions between emerging tumor cells and the immune system influence subsequent disease progression. This systematic review aimed to summarize current evidence on immune dynamics, tumor microenvironment (TME) remodeling, immune evasion mechanisms, and the potential implications of these processes for early therapeutic intervention. Methods: A systematic literature search was conducted in PubMed, Scopus, and Google Scholar for studies published between 1998 and 2026. Original articles, reviews, experimental studies, and clinical trials published in English were included if they addressed tumor immunology, the TME, immune evasion, or cancer stem cells (CSCs) in early-stage NSCLC. Studies focused exclusively on advanced disease, lacking relevance to the review topic, presenting insufficient methodological quality, or representing duplicate data were excluded. Following the screening process, 112 publications were included in the review. Results: The available evidence indicates that immune surveillance in early NSCLC involves complex and context-dependent interactions among T lymphocytes, natural killer cells, and macrophages. Progressive TME remodeling may contribute to a shift from anti-tumor immune activity toward immunosuppressive conditions through metabolic alterations and recruitment of regulatory immune populations. CSCs have been proposed as contributors to tumor heterogeneity and immune resistance, although their clinical significance remains under investigation. Disturbances in antigen presentation and activation of immune checkpoint pathways, including PD-1/PD-L1 (Programmed Cell Death Protein 1/Programmed Death-Ligand 1), were identified as key mechanisms of immune evasion. Preliminary clinical evidence suggests that neoadjuvant immunotherapy may provide benefit when applied in earlier stages of NSCLC, although further validation is required. Conclusion: Current evidence suggests that early immune alterations in NSCLC may influence tumor evolution and therapeutic responsiveness. Improved understanding of these processes could support optimization of perioperative treatment strategies; however, the clinical implications of many findings remain uncertain and require further investigation.

Unfavorable epidemiological forecasts indicating a significant increase in cancer incidence and mortality, as well as limitations of traditional cancer treatment methods, prompt the search for new, more effective therapeutic strategies. In response to the difficulties in treating cancer resulting from the significant heterogeneity of the tumor microenvironment and the presence of hypoxic and necrotic zones, anaerobic bacteria from the Clostridiaceae family, particularly those of the Clostridium genus, are attracting increasing interest. These bacteria can selectively grow in hypoxic areas of tumors while showing no affinity for healthy tissues. An additional advantage of these bacteria is their ability to produce toxins and enzymes that enable the lysis of cancer cells and activate the immune response. One of the most promising and distinctive strains is Clostridium novyi-NT, which lacks virulence factors and, in studies, has been shown to induce a strong cytolytic response. Modern genetic engineering has enabled the modification of Clostridiaceae bacteria to express enzymes that activate prodrugs, thereby significantly reducing systemic toxicity while targeting tumor tissue. Combining Clostridiaceae spore therapy with conventional treatments, such as chemotherapy, radiotherapy, or immunotherapy, significantly enhances their effectiveness, resulting in a highly beneficial synergistic therapeutic effect. The purpose of this review is to discuss the role and potential of Clostridiaceae bacteria in innovative anticancer therapies.

Biologically active peptides can be obtained with various research methods, depending on the starting material, biological activity, and intended use. To use the most efficient method, it is worth combining in silico and in vitro experiments. Among the tools that can support an in silico analysis are databases such as the Antimicrobial Peptide Database (AMPD) or BIOPEP-UWM. The aim of this study was to make an in silico hydrolysis of peptides with anticancer properties selected from the AMP database, using pepsin, trypsin, and chymotrypsin. Most peptides obtained had properties inhibiting ACE and dipeptidyl peptidase IV activity. Among the resulting peptides, those with the sequence AR, CF, ER, TF, IY, ER, AW, GF, TW, SK and IM are potentially resistant to peptidase from microbial action. An analysis of the peptides’ characteristics showed that peptides with the sequence AR, EK, ER and SK are well-soluble in water and have high affinity for protein and ligand binding. Peptides with the sequence TF, IL and PF are unstable. Thermostable peptides are PGL, IL, GL, IY, VF, PL, IM and QL. The results of the study may be used to design in vitro experiments.