Search Results (113,423)

Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer. Full article

Background: The involvement of the intratumoral microbiome in prostate cancer progression is becoming increasingly acknowledged. This study analyzed the microbiome of prostate cancer tissues from patients with localized prostate cancer (LPC, stages 1–2) and advanced prostate cancer (APC, stages 3–4) to determine its association with cancer progression. Methods: Paraffin-embedded tissue samples obtained during radical prostatectomy underwent 16S rRNA amplicon-based profiling. Results: The profile of the bacterial communities in LPC and APC differed remarkably. While species diversity remained stable, species richness (as determined by the ACE analysis) was significantly lower in APC, correlating with a decrease in Enhydrobacter (which is more abundant in LPC) and an increase in Lautropia (enriched in APC). The role of Lautropia in the progression of cancer was confirmed by in vitro studies employing cell lines from prostate cancer. Conclusions: These findings demonstrate the potential of microbiome-targeted interventions in the management of prostate cancer. Full article

Atrial fibrillation is the most frequent arrhythmia in elderly subjects. Cancer currently represents one of the most important causes of mortality and morbidity in the world. Often, the two pathologies coexist. Several pathophysiological mechanisms can lead to an increased risk of atrial fibrillation and cancer. Additionally, the same therapies used for cancer can increase the risk of developing atrial fibrillation. Our review aims to describe the pathophysiological mechanisms that promote the development of atrial fibrillation in cancer patients and explain the therapeutic opportunities and challenges of treating atrial fibrillation in patients with cancer. Full article

(1) Background: Early palliative care (EPC) is increasingly recognized as a key component of comprehensive cancer management, with evidence supporting improvements in quality of life, symptom control, and clinical outcomes in advanced malignancies. (2) Methods: This systematic review followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD42024623219). We searched PubMed, Embase, and the Cochrane CENTRAL Library for randomized controlled trials (RCTs) evaluating EPC in adults with advanced, incurable, or metastatic cancer. Eligible studies reported on at least one of the following: overall quality of life, symptom burden, or disease progression indicators. (3) Results: Forty-one RCTs met inclusion criteria. Despite heterogeneity in timing and structure, EPC consistently improved quality of life and reduced symptom burden in advanced cancer patients, with 32 trials demonstrating significant clinical benefit. Some studies also reported slowed disease progression. However, several RCTs showed no significant effects, highlighting variation in outcomes, possible subgroup effects, and challenges in implementation. Definitions and delivery of EPC varied widely, particularly in timing, frequency, and integration into oncology care. (4) Conclusions: These findings support the integration of EPC alongside disease-directed treatments, challenging the misconception that palliative care is only appropriate at the end of life and reinforcing its role early in the cancer care continuum. Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer entity in Germany, following basal cell carcinoma. Its incidence has increased fourfold over the past three decades. Early diagnosis and treatment are essential for achieving favorable outcomes. Our study aims to identify prognostic factors based on real-world data to improve follow-up protocols and raise clinical vigilance. Methods: We conducted a retrospective, monocenter analysis with a total of 124 patients with at least one cSCC thicker than 3 mm, treated at the Department of Dermatology, University Medical Center Mainz, between 2010 and 2020. Tumor-specific criteria were correlated with patient-specific data, such as gender, age, immunosuppression, UV exposure and mortality. Results: A higher incidence of cSCC was found on UV-exposed skin (91.1%); however, tumors on non-UV-exposed skin were on average thicker (6.55 mm vs. 9.25 mm, p = 0.011) and associated with higher metastasis rates (10.6% vs. 63.3%, p < 0.001). Immunosuppression was strongly associated with a younger age at diagnosis (74 years vs. 81 years), a higher metastasis rate (29% vs. 10.8%, p = 0.021) and a worse 5Y-OS-rate (36.1% vs. 97.8%, p = 0.04). SLNB was performed in eight patients, with one positive SLN identified (12.5%). Local recurrence was observed in 18.1% (n = 21) of patients who did not experience SLNB, whereas no local recurrences (0%) were reported in patients with SLNB (p = 0.349). Discussion: Tumors on non-UV-exposed areas were thicker and more often metastatic, suggesting delayed detection or more aggressive tumor subtypes. Immunosuppression was associated with worse outcomes, underscoring the need for intensified follow-up. SLNB was rarely performed, and larger studies are needed to assess its role. Full article

Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central nervous system (CNS) applications, including brain malignancies such as gliomas and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Microtubule-stabilizing agents, such as taxanes and epothilones, promote microtubule assembly and have shown efficacy in both tumour suppression and neuronal repair, though their CNS use is hindered by blood–brain barrier (BBB) permeability and neurotoxicity. Destabilizing agents, including colchicine-site and vinca domain binders, offer potent anticancer effects but pose greater risks for neuronal toxicity. This review highlights the mapping of nine distinct tubulin binding pockets—including classical (taxane, vinca, colchicine) and emerging (tumabulin, pironetin) sites—that offer new pharmacological entry points. We summarize the recent advances in structural biology and drug design, enabling MTAs to move beyond anti-mitotic roles, unlocking applications in both cancer and neurodegeneration for next-generation MTAs with enhanced specificity and BBB penetration. We further discuss the therapeutic potential of combination strategies, including MTAs with radiation, histone deacetylase (HDAC) inhibitors, or antibody–drug conjugates, that show synergistic effects in glioblastoma models. Furthermore, innovative delivery systems like nanoparticles and liposomes are enhancing CNS drug delivery. Overall, MTAs continue to evolve as multifunctional tools with expanding applications across oncology and neurology, with future therapies focusing on optimizing efficacy, reducing toxicity, and overcoming therapeutic resistance in brain-related diseases. Full article

Background: Merkel cell polyomavirus (MCPyV) has been established as an etiological agent in Merkel cell carcinoma (MCC), yet its role in other cutaneous neoplasms remains under investigation. The impact of the host’s immunogenetic characteristics on the persistence of Merkel cell polyomavirus (MCPyV) in non-melanoma skin cancer (NMSC) is not yet well understood. Objective: Our aim was to investigate the presence of MCPyV in various skin lesions, particularly NMSC, and its association with cytokine gene polymorphisms related to immune regulation. Methods: We analyzed 274 skin biopsies (lesional, perilesional, and healthy skin) from 84 patients undergoing dermatological evaluation. MCPyV DNA and polymorphisms in IL-6, IL-10, IFN-γ, and TNF-α genes were detected using PCR-based assays. Results: MCPyV was significantly more prevalent in NMSC and non-cancerous lesions than in surgical margins or healthy skin (p = 0.050 and 0.048, respectively). Concordance between lesion and margin samples was low (κ = 0.305), suggesting microenvironment-specific viral persistence. Notably, high-expression IL-10 genotypes (-1082 GG) and low-expression IL-6 genotypes (-174 AA) were significantly associated with MCPyV detection (p = 0.048 and p = 0.015, respectively). Conclusions: MCPyV preferentially localizes to NMSC lesions, particularly in individuals with immunogenetic profiles favoring viral persistence. Since the role of MCPyV in the pathogenesis of NMSC remains uncertain, our results highlight the need for further studies to clarify whether the lesion’s microenvironment supports viral persistence or indicates a more intricate interaction between the virus and the host, which could be significant for the development of skin cancer. Full article

Background/Objectives: Melanoma is an aggressive skin cancer with increasing incidence worldwide. Dermoscopy has revolutionized early melanoma detection, but most studies have focused on the general adult population. This study aims to analyze dermoscopic and histological differences in melanoma across age groups, evaluating whether specific patterns vary between younger and older patients. Methods: This retrospective study included 285 histopathological confirmed melanomas diagnosed at the Dermatology Clinic of the University of Turin between November 2021 and April 2024. Patients were stratified by age (<40 vs. ≥40 years), and statistical analyses (Chi-square, logistic regression) assessed differences in dermoscopic, histopathological, and anatomical parameters. Results: Younger patients showed a higher prevalence of growth-related features (e.g., pseudopods, OR = 5.43; asymmetric globules, OR = 2.33) and a thicker Breslow index (mean = 1.05 mm). Older patients exhibited more regression-associated signs (scar-like depigmentation, OR = 0.15; peppering, OR = 0.39), greater lesion size, and solar elastosis. Dermoscopic regression significantly predicted histological regression, with age-stratified analysis revealing peppering as a predictor in younger patients (p = 0.015) and scar-like depigmentation in older ones (p = 0.012). Conclusions: Melanoma exhibits distinct dermoscopic features depending on patient age, with growth-associated patterns being more common in younger individuals and regressive patterns predominating in older patients. These findings highlight the importance of age-specific diagnostic considerations in melanoma detection, potentially improving early diagnosis and patient outcomes. Full article

Chimeric antigen receptor (CAR)-engineered NK cells are a promising approach for targeted immunotherapy in Her2-positive cancers. This study aimed to generate anti-Her2 CAR-NK92 cells, to evaluate their selective cytotoxicity against Her2-positive cancer cells, and to isolate and characterize their released exosomes. NK92 cells were electroporated with piggyBac transposon vectors encoding anti-Her2 CAR and the helper transposase. Puromycin selection was performed to enrich the transduced cells. CAR and GFP expression were assessed by flow cytometry, and exosomes were isolated and characterized in terms of protein cargo and surface protein expression. Cytotoxicity was evaluated using real-time cell analysis against Her2-positive SK-BR3 cells and Her2-negative MCF-7 cells. Electroporation did not significantly affect NK92 cell viability. Puromycin selection efficiently enriched for CAR-expressing cells, with GFP positivity reaching 99.8% and a 15-fold increase in CAR surface expression compared to wild-type cells. CAR-NK92 cells demonstrated robust, Her2-specific cytotoxicity in a E:T-dependent manner, with the greatest effect observed at a 10:1 effector-to-target ratio. Exosomes derived from CAR-NK92 cells contained CAR molecules and selectively targeted Her2-positive cells. Anti-Her2 CAR-NK92 cells and their exosomes exhibit potent and selective cytotoxicity against Her2-positive cancer cells, supporting their potential as innovative immunotherapeutic agents for solid tumors. Full article

Alkyladenine DNA glycosylase (AAG) is a critical enzyme in the base excision repair (BER) pathway, responsible for removing a broad spectrum of alkylated DNA lesions. While AAG maintains genomic stability, dysregulated activity has been implicated in cancer development, drug resistance, and neurodegenerative diseases. This review synthesizes the current knowledge on AAG’s structure, catalytic mechanism, and polymorphic variants, highlighting their potential roles in disease pathogenesis. A comprehensive bioinformatics analysis of over 370 AAG single-nucleotide polymorphisms (SNPs) is presented, identifying ~40% as high-risk variants likely to impair enzymatic function. Notably, 151 SNPs were predicted to be damaging by multiple algorithms, including substitutions at catalytic residues and non-conserved sites with unknown functional consequences. Analysis of cancer databases (COSMIC, cBioPortal, NCBI) revealed 93 tumor-associated AAG variants, with 18 classified as high-impact mutations. This work underscores the need for mechanistic studies of AAG variants using structural biology, cellular models, and clinical correlation analyses. Deciphering AAG’s polymorphic landscape may unlock personalized strategies for cancer prevention and treatment. Full article

Background/Objectives: Cancer represents a significant health challenge, with high mortality and morbidity rates. Its diagnosis often triggers chronic stress, adversely affecting patient outcomes. Exercise has emerged as complementary therapy, enhancing treatment adherence and mitigating the side effects of chemotherapy. This study examines the effects of mild exercise during chemotherapy on patient anxiety. Methods: This prospective paired cohort study was conducted in the General Oncology Hospital of Kifisia “Agioi Anargyroi” in Athens, Greece. Adult cancer patients undergoing chemotherapy participated, excluding those with cognitive, hearing, or motor impairments, those who experienced side effects, or those who declined consent. Anxiety was measured before and after a 20-minute exercise routine performed during chemotherapy, using the Greek-translated State–Trait Anxiety Inventory (STAI). The exercise regimen included warm-up, full-body stretching, and cool-down exercises. Pre- and post-exercise scores were analyzed using the Wilcoxon signed-rank test. Results: Forty-five patients (20 women, 25 men; mean age 69.02 ± 10.62 years) with various cancer backgrounds participated. Pre-intervention anxiety levels were in the borderline “moderate” range, dropping post-exercise to the “low” range. Mean STAI scores decreased from 37.73 ± 13.33 to 32.00 ± 14.22 (p < 0.0001), with a medium-large effect size (Cohen’s d for paired samples = −0.646). No significant correlation was found between age and anxiety scores. Discussion: This study found a significant short-term reduction in anxiety, suggesting that incorporating mild exercise during chemotherapy may help in alleviating patient stress. The medium-to-large effect size supports the potential for meaningful short-term benefits. Conclusions: Incorporating mild exercise during chemotherapy may help reduce anxiety and psychological burden. These findings underscore the need for more comprehensive research in larger, more diverse populations to better understand the benefits of incorporating mild exercise during chemotherapy. Full article

Background: Radiation dose escalation for locally advanced pancreatic cancer (LAPC) using stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) or computed tomography (CT)-guided moderately hypofractionated ablative radiation therapy (HART) can achieve favorable outcomes although have not previously been compared. Methods: We performed a multi-center retrospective analysis of SMART (50 Gy/5 fractions) vs. HART (75 Gy/25 fractions or 67.5 Gy/15 fractions with concurrent capecitabine) for LAPC. Gray’s test and Cox proportional regression analyses were performed to identify factors associated with local failure (LF) and overall survival (OS). Results: A total of 211 patients (SMART, n = 91; HART, n = 120) were evaluated, and none had surgery. Median follow-up after SMART and HART was 27.0 and 40.0 months, respectively (p < 0.0002). SMART achieved higher gross tumor volume (GTV) coverage and greater hotspots. Two-year LF after SMART and HART was 6.5% and 32.9% (p < 0.001), while two-year OS was 31.0% vs. 35.3% (p = 0.056), respectively. LF was associated with SMART vs. HART (HR 5.389, 95% CI: 1.298–21.975; p = 0.021) and induction mFOLFIRINOX vs. non-mFOLFIRINOX (HR 2.067, 95% CI 1.038–4.052; p = 0.047), while OS was associated with CA19-9 decrease > 40% (HR 0.725, 95% CI 0.515–0.996; p = 0.046) and GTV V120% (HR 1.022, 95% CI 1.006–1.037; p = 0.015). Acute grade > 3 toxicity was similar (3.3% vs. 5.8%; p = 0.390), while late grade > 3 toxicity was less common after SMART (2.2% vs. 9.2%; p = 0.037). Conclusions: Ablative SMART and HART both achieve favorable oncologic outcomes for LAPC with minimal toxicity. We did not observe an OS difference, although technical advantages of SMART might improve target coverage and reduce LF. Full article

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article

Background: Double-valve infective endocarditis (DVIE) accounts for 15–20% of all endocarditis and represents a challenge due to the increased incidence of embolic events and congestive heart failure compared to infective endocarditis (IE) affecting one valve. This study aims to evaluate patients’ characteristics, surgical procedures, complications, and mortality associated with DVIE in our tertiary hospital in Italy. The Endocarditis Registry STEADY includes patients admitted with IE from January 2009 to March 2024 (n = 398). Sixty-three of them (16%) had DVIE. Methods: We conducted a retrospective single-center observational study, analyzing demographic, clinical, and microbiological data in DVIE patients, comparing those treated surgically (surgical group, SG) with those treated medically (non-surgical group, NSG). Results: The groups were homogeneous in age, microbiological yields, type of valve involved, and risk factors for infective endocarditis. The surgical group presented significantly more cancer history, intracardiac complications, and new-onset arrhythmias compared to the non-surgical group. Median hospital stay was similar in both groups. In SG, the most common postoperative complication was new rhythm disorders; other complications such as cardiac tamponade, pericardial effusion, and pneumothorax were rare. In-hospital mortality was similar between groups; however, one-year survival was higher in the surgical group (72% vs. 54%, p = 0.031). In our series, 16 patients were over 75 years old (25%), and 7 of them (44%) underwent cardiac surgery. One-year survival in the surgical group was also higher in this subgroup. Conclusions: Surgical treatment, when indicated, may improve the prognosis of patients with DVIE, including elderly patients. Full article

Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous T cells, while adoptive cell therapy produces therapeutic T cells with high functionality and defined cancer specificity. While CAR engineering successfully targets cancer surface antigens, TCR engineering enables targeting of the entire cancer proteome, including mutated neo-antigens. To date, TCR engineering strategies have focused on the identification of target cancer antigens recognised by well-characterised therapeutic TCRs. In this review, we explore whether antigen-focused approaches could be complemented by TCR-focused approaches, whereby information of the TCR repertoire of individual patients provides the basis for selecting TCRs to engineer autologous T cells for adoptive cell therapy. We discuss how TCR clonality profiles, distribution in T cell subsets, and bioinformatic screening against continuously improving TCR databases can guide the selection of TCRs for therapeutic application. We further outline in vitro approaches to prioritise TCR candidates to confirm cancer reactivity and exclude recognition of healthy autologous cells, which could provide validation for their therapeutic use even when the target antigen remains unknown. Full article