Acta Naturae最新文献

{"title":"Extracellular Vesicles As a Source of Biomarkers for Cancer Diagnosis.","authors":"L A Ovchinnikova, Y A Lomakin","doi":"10.32607/actanaturae.27591","DOIUrl":"10.32607/actanaturae.27591","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are secreted by nearly all mammalian cells and play a major role in intercellular communication via the transport of various active biomolecules. In cancer, pathological EVs contribute to tumor progression by participating in metastasis, angiogenesis, and immune evasion. Recent advancements in EV research have revealed their potential as noninvasive biomarkers. This review addresses the latest advancements in EV isolation and characterization techniques, elucidates the molecular mechanisms underlying EV biogenesis, and examines their functional roles in cancer progression. Furthermore, we discuss emerging strategies that leverage EV profiling and molecular composition analysis, in conjunction with liquid biopsy technologies, offering possible breakthroughs in early cancer diagnosis and treatment monitoring. By synthesizing these insights, this review emphasizes the growing significance of EVs as versatile and powerful diagnostic tools in oncology.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"28-40"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Key Substitutions in the Chromophore Environment of mKate2 Produce an Enhanced FusionRed-like Red Fluorescent Protein.","authors":"D A Ruchkin, A S Gavrikov, D V Kolesov, A Yu Gorokhovatsky, T V Chepurnykh, A S Mishin, E G Maksimov, N V Pletneva, V Z Pletnev, A M Pavlova, V A Nikitin, A M Bogdanov","doi":"10.32607/actanaturae.27545","DOIUrl":"10.32607/actanaturae.27545","url":null,"abstract":"<p><p>Red fluorescent proteins (RFPs) are often probes of choice for living tissue microscopy and whole-body imaging. When choosing a specific RFP variant, the priority may be given to the fluorescence brightness, maturation rate, monomericity, excitation/emission wavelengths, and low toxicity, which are rarely combined in an optimal way in a single protein. If additional requirements such as prolonged fluorescence lifetime and/or blinking ability are applied, the available repertoire of probes could dramatically narrow. Since the entire diversity of conventional single-component RFPs belongs to just a few phylogenetic lines (DsRed-, eqFP578- and eqFP611-derived being the major ones), it is not unexpected that their advantageous properties are split between close homologs. In such cases, a systematic mutagenetic analysis focusing on variant-specific amino acid residues can shed light on the origins of the distinctness between related RFPs and may aid in consolidating their strengths in new RFP variants. For instance, the protein FusionRed, despite being efficient in fluorescence labeling thanks to its good monomericity and low cytotoxicity, has undergone considerable loss in fluorescence brightness/lifetime compared to the parental mKate2. In this contribution, we describe a fast-maturing monomeric RFP designed semi-rationally based on the mKate2 and FusionRed templates that outperforms both its parents in terms of molecular brightness, has extended fluorescence lifetime, and displays a spontaneous blinking pattern that is promising for nanoscopy use.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"110-117"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monomeric α-Synuclein Real-Time Induced Conversion: A New Approach to the Diagnostics of Neurodegenerative Synucleinopathies with Weak RT-QuIC Responses.","authors":"D A Orlova, A A Kudriaeva, N A Kolotyeva, E O Ivanova, E Yu Fedotova, P P Tregub, A B Salmina, S N Illarioshkin, A A Belogurov","doi":"10.32607/actanaturae.27530","DOIUrl":"10.32607/actanaturae.27530","url":null,"abstract":"<p><p>Neurodegenerative disorders classified as synucleinopathies (Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy) are characterized by the accumulation of aberrant α-synuclein aggregates in neurons and glial cells. These diseases manifest clinically several years after the initial formation of pathological protein aggregates in the brain, making early and accurate diagnosis challenging. In recent years, a new method, which is based on real-time quaking-induced conversion (RT-QuIC) of α-synuclein, has been developed and validated. This technology holds great promise as a powerful diagnostic tool for the early and precise identification of synucleinopathies, potentially opening new horizons in the study of neurodegenerative diseases. RT-QuIC detects misfolded α-synuclein aggregates in human physiological fluids by introducing an excess of recombinant α-synuclein, which undergoes conformational conversion in an exponential, prion-like manner. The production of high-quality recombinant α-synuclein is a critical step in the effective application of this method, as protein purity significantly affects the sensitivity and specificity of the assay - key factors in its diagnostic utility. Using a three-step chromatographic purification protocol, we produced recombinant monomeric α-synuclein with a purity exceeding 97% from the periplasmic fraction of bacterial cells. While higher purity increases the assay duration, it also reduces the background signal and permits extended incubation times, which are essential for reliably detecting synucleinopathies with weak RT-QuIC responses, such as the cerebellar subtype of multiple-system atrophy. The data presented support the conclusion that optimized components of the RT-QuIC system will enable an accurate diagnosis of neurodegenerative synucleinopathies.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"110-117"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emergence of a Novel Insertional Mutation in the BCR::ABL/p210 Oncogene in B-Cell Acute Lymphoblastic Leukemia (B-ALL) Correlates with the Development of Resistance to Several Tyrosine Kinase Inhibitors.","authors":"K V Bogdanov, E S Kudryavtseva, Y N Lobacheva, O V Merzlikina, Y V Mirolyubova, R A Vlasik, R Sh Badaev, E G Lomaia","doi":"10.32607/actanaturae.27539","DOIUrl":"10.32607/actanaturae.27539","url":null,"abstract":"<p><p>A patient with an immunophenotype characteristic of B-cell acute lymphoblastic leukemia (B-ALL) was found to carry the chromosomal translocation t(9;22)(q34;q11), or Philadelphia (Ph) chromosome and less common variant of the chimeric oncogene BCR::ABL/p210. No additional mutations in the BCR::ABL gene, including point mutations, insertions, or deletions, were identified in the disease onset characterized by elevated blast cell (77.6%) and leukocyte (48×109/L) counts. Ph+ALL-2012m chemotherapy with imatinib (600 mg) and two consolidation phases resulted in complete hematologic remission and a profound molecular response. However, six months later, the patient had relapsed (blasts: 15%, BCR::ABL/p210: 105%). Three weeks after the initiation of dasatinib therapy (100 mg), the number of blasts had decreased to 4.8%, while the expression level of BCR::ABL/p210 had dropped to 11.8%. Sanger sequencing identified two mutations in the BCR::ABL oncogene; namely, the point mutation F317L and a new insertion of nine nucleotides previously not detected. In the latter case, the amino acid lysine at position 294 was replaced by four new amino acid residues: K294SPSQ. Therapy with bosutinib and inotuzumab led to the disappearance of one leukemia clone with the F317L mutation, but the presence of another clone carrying a nine-nucleotide insertion was observed. The switch to ponatinib+blinatumomab chemotherapy was effective, resulting in the disappearance of the insertion. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an available HLA-matched unrelated donor resulted in complete clinical and hematologic remission, including a complete molecular response. Six months after allo-HSCT, minimal residual disease monitoring showed maintenance of complete remission.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"52-57"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Assisted Reproductive Technologies on De Novo Mutations.","authors":"N A Arakelyan, J Vasilevska, E I Rogaev","doi":"10.32607/actanaturae.27589","DOIUrl":"10.32607/actanaturae.27589","url":null,"abstract":"<p><p>Recent advances in assisted reproductive technologies (ART) have revolutionized human reproduction, offering hope to millions of couples facing infertility issues. At the same time, concerns persist regarding the potential impact of ART on the genomic integrity of offspring conceived through these techniques. Specifically, questions abound about the effects of these techniques on the incidence of de novo mutations (DNMs), which are genetic alterations that arise spontaneously in the germline or during early embryonic development and are implicated in various human diseases. The extent to which ART directly affects the rate of de novo mutations has been the subject of ongoing debate. This review explores recent studies that have investigated the relationship between ART and DNMs. It underscores the necessity for further research to clarify the clinical implications and long-term consequences of ART.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"4-14"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of HiMoRNA and RNAChrom: Validation of the Functional Role of Long Non-coding RNAs in the Epigenetic Regulation of Human Genes Using RNA-Chromatin Interactome Data.","authors":"I S Ilnitskiy, G K Ryabykh, D A Marakulina, A A Mironov, Yu A Medvedeva","doi":"10.32607/actanaturae.27543","DOIUrl":"10.32607/actanaturae.27543","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) play a crucial role in the epigenetic regulation of gene expression by recruiting chromatin-modifying proteins to specific genomic loci. Two databases, previously developed by our groups, HiMoRNA and RNA-Chrom, provide valuable insights into this process. The former contains data on epigenetic modification regions (peaks) correlated with lncRNA expression, while the latter offers genome-wide RNA-chromatin interaction data for tens of thousands of RNAs. This study integrated the two resources to generate experimentally supported, interpretable hypotheses regarding lncRNA-mediated epigenetic gene expression regulation. We adapted the web interfaces of HiMoRNA and RNA-Chrom to enable the retrieval of chromatin contacts for each \"lncRNA-pigenetic modification-ssociated gene\" triad from HiMoRNA, either at specific genomic loci or genome-wide via RNA-Chrom. The integration analysis revealed that for the lncRNAs MALAT1, HOXC-AS2, NEAT1, NR2F1-AS1, PVT1, and MEG3, most HiMoRNA peaks are located within 25 kb of their RNA-Chrom contacts. Further investigation confirmed the RNA-hromatin contacts of MIR31HG and PVT1 lncRNAs, with HiMoRNA peaks for H3K27ac and H3K27me3 marks in the loci of the genes <i>GLI2</i> and <i>LATS2</i>, respectively, which are known to be regulated by these RNAs. Thus, the integration of HiMoRNA and RNA-Chrom offers a powerful platform to elucidate the role of specific lncRNAs in the regulation of histone modifications at both individual loci and genome-wide levels. We expect this integration to help significantly advance the functional annotation of human lncRNAs.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"98-109"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Chalcone Synthase Genes from Garlic (Allium sativum L.) and Their Expression Levels in Response to Stress Factors.","authors":"O K Anisimova, A V Shchennikova, E Z Kochieva, M A Filyushin","doi":"10.32607/actanaturae.27639","DOIUrl":"10.32607/actanaturae.27639","url":null,"abstract":"<p><p>A plant's defense response involves the accumulation of flavonoids, whose biosynthetic pathway in garlic <i>Allium sativum</i> L. remains not characterized. In this work, we identified eight <i>AsCHS1-8</i> genes of chalcone synthases in the <i>A. sativum</i> genome which presumably catalyze the first stage of flavonoid synthesis in garlic plants. These genes were found to be localized on 4 chromosomes: <i>AsCHS2</i>, <i>6-8</i> contain 1 to 2 introns, whereas <i>AsCHS1</i>, <i>3-5</i> are intronless. The analysis of the organ-specific gene expression profiles revealed significant transcript levels for <i>AsCHS3</i> and <i>8</i>. Only <i>AsCHS8</i> was shown to change its expression level in response to abiotic stressors (salinity, drought, cold) and exogenous phytohormones (abscisic acid, methyl jasmonate). These findings suggest that two out of the eight genes, <i>AsCHS3</i> and <i>8</i>, control flavonoid synthesis during garlic development, with <i>AsCHS8</i> being the most active chalcone synthase gene. The other six genes (<i>AsCHS1</i>, <i>2, 4-7</i>) may be involved in flavonoid biosynthesis in highly specialized cells/tissues/organs or the developmental stages of the garlic plant. Our results on the identification and characterization of garlic chalcone synthase genes <i>AsCHS1-8</i> may facilitate further analysis of the mechanisms that regulate stress adaptation in <i>A. sativum</i> and other <i>Allium</i> species. A plant's defense response involves the accumulation of flavonoids, whose biosynthetic pathway in garlic <i>Allium sativum</i> L. remains not characterized. In this work, we identified eight <i>AsCHS1-8</i> genes of chalcone synthases in the <i>A. sativum</i> genome which presumably catalyze the first stage of flavonoid synthesis in garlic plants. These genes were found to be localized on 4 chromosomes: <i>AsCHS2</i>, <i>6-8</i> contain 1 to 2 introns, whereas <i>AsCHS1</i>, <i>3-5</i> are intronless. The analysis of the organ-specific gene expression profiles revealed significant transcript levels for <i>AsCHS3</i> and <i>8</i>. Only <i>AsCHS8</i> was shown to change its expression level in response to abiotic stressors (salinity, drought, cold) and exogenous phytohormones (abscisic acid, methyl jasmonate). These findings suggest that two out of the eight genes, <i>AsCHS3</i> and <i>8</i>, control flavonoid synthesis during garlic development, with <i>AsCHS8</i> being the most active chalcone synthase gene. The other six genes (<i>AsCHS1</i>, <i>2, 4-7</i>) may be involved in flavonoid biosynthesis in highly specialized cells/tissues/organs or the developmental stages of the garlic plant. Our results on the identification and characterization of garlic chalcone synthase genes <i>AsCHS1-8</i> may facilitate further analysis of the mechanisms that regulate stress adaptation in <i>A. sativum</i> and other <i>Allium</i> species.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"41-51"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of TIL-based Cellular Products for Cancer Immunotherapy: Current Insights and the Challenges.","authors":"D V Kuznetsova, T V Petrova","doi":"10.32607/actanaturae.27559","DOIUrl":"10.32607/actanaturae.27559","url":null,"abstract":"<p><p>Tumor-infiltrating T lymphocytes (TILs) are a population of T cells present in tumor tissue and enriched in tumor antigen-specific clones. TILs participate in the adaptive antitumor immune response, which makes them a promising candidate for cancer immunotherapy. The concept framing this type of therapy involves the extraction of T cells from a patient's tumor, followed by their in vitro expansion and reinfusion into the same patient in large quantities. This approach enhances the antitumor immune response and allows one to affect cancer cells resistant to other types of treatment. In 2024, the first TIL-based drug was approved for melanoma treatment. The possibility of using TILs for treating other solid tumors is currently being considered, and novel methods aiming to increase the efficiency of generating TIL cultures from tumor tissues in vitro are being developed. However, despite the significant progress achieved in this area, there remain unresolved issues and problems, including the lack of standardized protocols for obtaining, expanding, and cryopreserving TILs, the complexity related to their isolation and the duration of that, as well as insufficient efficiency. Our review focuses on the concept of immunotherapy using TILs, the main stages involved in generating a TIL-based cellular product, associated problems, and further steps in the production of TIL cultures that aim to improve efficiency as relates to production and ensure a wider application of the therapy.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"15-27"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Drosophila Zinc Finger Protein Aef1 Colocalizes with Enhancers and Is Involved in the Transcriptional Regulation of Numerous Genes.","authors":"N E Vorobyeva, J V Nikolenko, A N Krasnov","doi":"10.32607/actanaturae.27556","DOIUrl":"10.32607/actanaturae.27556","url":null,"abstract":"<p><p>In our previous studies, we demonstrated that the Drosophila zinc finger protein Aef1 interacts with the SAGA DUB module. The Aef1 binding sites colocalize with the SAGA histone acetyltransferase complex and the dSWI/SNF chromatin remodeling complex, as well as the origin recognition complex (ORC). Aef1 predominantly localizes with the promoters of active genes (55% of all sites) and can be involved in transcriptional regulation. In this study, we showed that Aef1 binding sites in Drosophila S2 cells, located outside gene promoters, are nucleosome-depleted regions and colocalize with the SAGA, dSWI/SNF, and ORC complexes. Aef1 binding sites colocalize with the CBP protein and the H3K27Ac histone tag, which is considered to be an active enhancer mark. An RNA-Seq experiment was conducted in Drosophila S2 cells, both normal and with RNA interference targeting the Aef1 protein, to study the role played by the Aef1 protein in transcriptional regulation. The Aef1 protein was shown to affect the transcription of 342 genes, more than half of those (178 genes) containing Aef1 at their promoters or enhancers. Hence, we infer that the Aef1 protein is recruited to both promoters and enhancers and is involved, both directly and indirectly, in the regulation of the transcription of the respective genes.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 2","pages":"58-63"},"PeriodicalIF":2.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12322892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination with a Low Dose of Doxorubicin Further Boosts the Antitumor Effect of SLURP-1 In Vivo and Associates with EGFR Down-Regulation.","authors":"O V Shlepova, M L Bychkov, V O Shipunova, E I Shramova, M A Shulepko, T Y Gornostaeva, E A Kiseleva, I D Kukushkin, V A Kazakov, E A Tukhovskaya, I A Dyachenko, A N Murashev, Z O Shenkarev, S M Deyev, M P Kirpichnikov, E N Lyukmanova","doi":"10.32607/actanaturae.27526","DOIUrl":"10.32607/actanaturae.27526","url":null,"abstract":"<p><p>Skin cancers such as squamous cell carcinoma (SCC) are among the most aggressive types of tumors. They come with a high rate of growth, metastasis, and frequently occurring chemoresistance. Smoking is one of the risk factors for SCC progression, and the α7 nicotinic acetylcholine receptor (α7-nAChR) is a promising target for SCC therapy. Human secreted protein SLURP-1 is an auto/paracrine regulator of epithelial homeostasis and a selective negative allosteric modulator of α7-nAChR. Recently, we demonstrated the high efficiency of the therapy based on the recombinant SLURP-1 in controlling SCC cell growth and metastasis <i>in vivo</i>. The anti-tumor effect of SLURP-1 was mediated through interaction with both α7-nAChR and the epidermal growth factor receptor (EGFR). Cytotoxic antibiotic doxorubicin has been proposed for the SCC therapy; however, its use is limited due to the high toxicity. In this study we investigated the use of an enhanced SLURP-1 dose and of a combination of SLURP-1 with low-dozen doxorubicin for SCC treatment of mice xenografted with squamous cell carcinoma A431 cells. An increased SLURP-1 dose didn't significantly enhance the efficiency of the therapy. However, the combination with doxorubicin further enhanced the anti- tumor activity of SLURP-1 and dramatically suppressed metastasis. The effect from the combined therapy was accompanied by down-regulation of EGFR expression in tumors. Direct inhibition of EGFR activation by SLURP-1 was shown. No toxicity of the combined therapy was encountered. Our data indicate that the combination of SLURP-1 with chemotherapy in lower doses is a promising approach in SCC treatment and should be further studied.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":"17 1","pages":"87-96"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}