Search Results (19,734)

Advanced therapy medicinal products (ATMPs), especially effective against cancer, remain costly due to their reliance on genetically modified T cells. Contamination during production is a major concern, as traditional quality control methods involve samplings, which can themselves introduce contaminants. It is therefore necessary to develop methods for detecting contamination without sampling and, if possible, in real time. In this article, we present a white light spectroscopy method that makes this possible. It is based on shape analysis of the absorption spectrum, which evolves from an approximately Gaussian shape to a shape modified by the 1/λ component of bacterial absorption spectra when contamination develops. A warning value based on this shape descriptor is proposed. It is demonstrated that a few hours are sufficient to detect contamination and trigger an alarm to quickly stop the production. This time-saving should reduce the cost of these new drugs, making them accessible to as many people as possible. This method can be used regardless of the type of contaminants, provided that the shape of their absorption spectrum is sufficiently different from that of pure T cells so that the shape descriptor is efficient. Full article

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Background/Objectives: Aberrant expression of high-mobility group protein B1 (HMGB1) has been linked to cancer development and progression. Methods: To better comprehend the role of HMGB1 expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: Strong HMGB1 staining occurred in almost all normal cell types and in most cancers. Of 11,808 evaluable cancers, only 7.8% showed complete absence of HMGB1 staining (HMGB1 deficiency) while 9.9% showed 1+, 25.0% showed 2+, and 57.2% showed 3+ HMGB1 positivity. Absence of HMGB1 staining mostly occurred in pheochromocytoma (90.0%), seminoma (72.4%), gastrointestinal stromal tumor (28.6%), adrenal cortical carcinoma (25.0%), and Hodgkin’s lymphoma (25.0%). Low HMGB1 staining was linked to poor histologic grade (p < 0.0001), advanced pT stage (p < 0.0001), high UICC stage (p < 0.0001), and distant metastasis (p = 0.0413) in clear cell renal cell carcinoma, invasive tumor growth in urothelial carcinoma (pTa vs. pT2–4, p < 0.0001), mismatch repair deficiency (p = 0.0167) in colorectal cancers, and advanced pT stage in invasive breast carcinoma of no special type (p = 0.0038). Strong HMGB1 staining was linked to nodal metastases in high-grade serous ovarian carcinomas (p = 0.0213) and colorectal adenocarcinomas (p = 0.0137), as well as to poor histological grade in squamous cell carcinomas (p = 0.0010). Conclusions: HMGB1 deficiency and reduced HMGB1 expression occur in a broad range of different tumor entities. Low rather than strong HMGB1 staining is often linked to an aggressive tumor phenotype. Whether HMGB1 deficiency renders cells susceptible to specific drugs remains to be determined. Full article

Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment. Full article

Tumor heterogeneity encompasses genetic, epigenetic, and phenotypic diversity, impacting treatment response and resistance. Spatial heterogeneity occurs both inter- and intra-lesionally, while temporal heterogeneity results from clonal evolution. High-throughput technologies like next-generation sequencing (NGS) enhance tumor characterization, but conventional biopsies still do not adequately capture genetic heterogeneity. Liquid biopsy (LBx), analyzing circulating tumor DNA (ctDNA), provides a minimally invasive alternative, offering real-time tumor evolution insights and identifying resistance mutations overlooked by tissue biopsies. This study evaluates the capability of LBx to capture tumor heterogeneity by comparing genetic profiles from multiple metastatic lesions and LBx samples. Eight patients from the Augsburger Longitudinal Plasma Study with various types of cancer provided 56 postmortem tissue samples, which were compared against pre-mortem LBx-derived circulating-free DNA sequenced by NGS. Tissue analyses revealed significant mutational diversity (4–12 mutations per patient, VAFs: 1.5–71.4%), with distinct intra- and inter-lesional heterogeneity. LBx identified 51 variants (4–17 per patient, VAFs: 0.2–31.1%), which overlapped with mutations from the tissue samples by 33–92%. Notably, 22 tissue variants were absent in LBx, whereas 18 LBx-exclusive variants were detected (VAFs: 0.2–2.8%). LBx effectively captures tumor heterogeneity, but should be used in conjunction with tissue biopsies for comprehensive genetic profiling. Full article

Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article

Dose-dense chemotherapy shortens the interval between chemotherapy cycles and has shown improved outcomes in high-risk breast cancer patients. We retrospectively evaluated the efficacy and safety of dose-dense chemotherapy in 80 breast cancer patients treated at our hospital from 2020 to 2024. The regimen included epirubicin and cyclophosphamide followed by paclitaxel or docetaxel, with pegfilgrastim support. The overall treatment completion rate was 82.5%. Of the 80 patients, 55 underwent neoadjuvant chemotherapy, and the pathological complete response rate was significantly higher in triple-negative breast cancer (59.1%) compared to that in luminal-type cancer (9.1%). Common adverse events included anemia, liver dysfunction, myalgia, and peripheral neuropathy. Febrile neutropenia occurred in 8.8% of patients, with some cases linked to pegfilgrastim body pod use, particularly in individuals with low subcutaneous fat. Notably, two patients developed pneumocystis pneumonia, potentially associated with steroid administration. Despite these toxicities, most were manageable and resolved after treatment. Our findings support the efficacy of dose-dense chemotherapy, particularly in triple-negative breast cancer, while highlighting the importance of individualized supportive care and vigilance regarding hematologic and infectious complications. Full article

Gastric cancer (GC) is among the most common and deadliest types of cancer, with a poor prognosis primarily due to late-stage detection and the presence of cancer stem cells (CSCs). This study investigates the mechanisms regulating extracellular adenosine levels in gastric cancer stem-like cells (GCSCs) derived from the MKN-74 cell line. Our results show that GCSCs release more ATP into the extracellular medium and exhibit higher levels of CD39 expression, which enables them to hydrolyze a greater amount of ATP. Furthermore, we also found that GCSCs possess a greater capacity to hydrolyze AMP, primarily due to the activity of the CD73 protein, with no significant changes in CD73 transcripts and protein levels between GCSCs and differentiated cells. Additionally, adenosine transport is primarily mediated by members of the equilibrative nucleoside transporter (ENT) family in GCSCs, where a significant increase in the expression level of the ENT2 protein is observed compared to non-GCSCs MKN-74 cells. These findings suggest that targeting the adenosine metabolism pathway in GCSCs could be a potential therapeutic strategy for gastric cancer. Full article

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

Background/Objectives: The increasing incidence rates of keratinocyte carcinoma (KC), particularly in fair-skinned populations, call for efforts to intensify health education of the general population in addressing this prevalent skin cancer type. As a preparatory step, this systematic review summarizes the published research on the knowledge and risk perception regarding KC among individuals without medical training. Methods: The review was registered in PROSPERO (CRD42024618851) and adheres to PRISMA guidelines. The databases PubMed, Scopus, Web of Science, PsycArticles, and PsycINFO were searched on 30 July 2024. Studies were eligible if knowledge and/or risk perception was assessed in lay people. Risk of bias (ROB) was assessed with the Joanna Briggs Institute checklist for prevalence studies. Comparable outcomes (e.g., awareness of terms for KC) were meta-analyzed. Results: Included reports (n = 17) were published between 1991 and 2024 with 16,728 individuals assessed. Awareness for the most common type of KC, basal cell carcinoma (BCC), was low (20.75% of respondents (95% confidence interval (CI): 15.24–27.61)), while more respondents were familiar with colloquial terms (60.9–72.8%). Meta-analysis indicated an underestimation of the frequency of KC, with only 7.21% (CI: 4.03–12.58) identifying BCC as the most common type of skin cancer. Furthermore, concern about developing KC as assessed in only two overlapping studies was reported by only 25–30% of respondents, indicating a significant gap in risk awareness and a lack of research on risk perception regarding KC. Conclusions: This review highlights the need for targeted health education interventions to improve knowledge and preventive behaviors regarding KC. Given the limitations of the included studies, characterized by high ROB, heterogeneity of results, and a lack of standardized assessment tools, further research is essential to enhance the understanding and awareness of KC in diverse populations. Full article

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Coffee is one of the most widely consumed beverages globally, with over 60% of Americans drinking it daily. This review examines coffee’s multifaceted impact on health and well-being, drawing on decades of research. Overall, the consensus is that moderate coffee intake is more beneficial than harmful across a wide range of health outcomes. Numerous large-scale, prospective cohort studies from around the world have consistently shown that moderate coffee consumption—typically three to five cups per day—is associated with reduced overall mortality and lower risk of major diseases such as cardiovascular diseases, diabetes, stroke, respiratory conditions, cognitive decline, and potentially several types of cancer, including liver and uterine cancers. Both caffeinated and decaffeinated coffee have shown benefits. The addition of sugar and cream to coffee may attenuate coffee’s positive health effects. Despite historical concerns, coffee consumption is not linked to increased risks of cancer, hypertension, or arrhythmia. However, some concerns remain. For pregnant women, coffee consumption should be limited to lower amounts, such that the daily intake of caffeine does not exceed 200 mg/day. Also, excessive caffeinated coffee intake may cause anxiety or sleep disturbances. Coffee’s health-promoting mechanisms include improved glucose balancing, increased physical activity, increased fat oxidation, improved lung function, and reduced inflammation. Beyond mortality and chronic diseases, coffee consumption affects many aspects of well-being: it supports hydration, boosts mental acuity, enhances physical performance, and may aid bowel recovery after surgery. While the field is well-studied via long-term observational cohorts, future research should focus on randomized controlled trials, Mendelian randomization studies, and granular analyses of coffee types and additives. Full article

Background/Objectives: Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. Methods: We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. Results: Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. Conclusions: Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes. Full article