Search Results (124,332)

Microwave-assisted polymerization is a transformative technique for synthesizing conductive polymers such as polypyrrole (PPy). Unlike conventional chemical or electrochemical methods that rely on external heating or electrode mediated oxidation, microwave irradiation induces volumetric and selective heating through dipole orientation and ionic conduction, which leads to faster reaction kinetics, improved uniformity and higher yields. This review highlights the fundamental mechanisms governing microwave polymer interactions, compares conventional and microwave-assisted polymerization routes and traces the evolution of pyrrole polymerization. Special emphasis is placed on the microwave-synthesized PPy composites and their superior electrochemical performance in energy storage, sensing and biomedical applications. Case studies of graphene/PPy, PPy–metal oxide (e.g., SnO₂@PPy nanotubes) and magnetic ferrite hybrids (e.g., BaFe₁₂O₁₉/PPy) nanocomposites demonstrate enhanced electrical conductivity, specific capacitance and more uniform nanostructures. Beyond energy storage, microwave polymerization techniques have led to the development of PPy composites that are used for sensing, antimicrobial activity and photothermal cancer therapy, highlighting the technique’s versatility across biomedical sciences. Reactor scale up, temperature and pressure control under sealed conditions, reproducibility and deeper mechanism understanding of how microwave radiation influences nucleation, chain growth, doping and charge transport were identified as the outstanding challenges that must be addressed to transform microwave-assisted synthesis from pilot to industrial scale. Overall, microwave-assisted polymerization is on its way to becoming a mainstream, energy efficient method for manufacturing high performance polymer composite materials. Full article

Background/Objectives: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Understanding its epidemiological characteristics is essential for guiding public health strategies. In this study, we characterized the epidemiological profiles that may contribute to the risk of ALL in children in southern Brazil. Methods: Clinical and epidemiological data from 71 children (1–15 years old) admitted and newly diagnosed with ALL at four hospitals in Curitiba, Paraná, Brazil, were retrieved and analyzed. Results: Among the 71 children with ALL, the majority were male (n = 43, 60.6%), with an age range of 1–3 years (n = 26, 36.6%), self-identified as White (n = 47, 66.2%), and were born in Paraná state (n = 61, 85.9%). Nearly half had a family history of cancer (n = 33, 46.5%), primarily among grandparents (n = 36, 61%). Parental environmental exposures included smoking (n = 30, 42.3%) and occupational exposure to chemicals or radiation (n = 17, 23.9%). At diagnosis, most patients (n = 43, 60.5%) had a bone marrow blast count > 70%, and 27 patients (38%) had a peripheral blood blast count > 70%. B-cell ALL was the predominant subtype (n = 61, 85.9%). In B-cell ALL cases, the most frequent molecular subtype was high hyperdiploidy (n = 17, 23.9%). White blood cell counts differed significantly between the B-cell ALL and T-cell ALL groups (p = 0.029). Conclusions: Our findings provide insights into ALL epidemiology in southern Brazil and highlight regional differences across the country. Full article

China recently became the 155th country to provide free vaccination to all 13-year-old girls with two doses of a domestic bivalent HPV vaccine in October 2025. Such a policy change aligns with the Immunization Agenda 2030, which expects more investment of domestic resources into immunization rather than heavily depending on external donor funding support. This review examines the policy-making evolution process and analyzes how the final decision was made at the national level, using the Multiple Streams Framework. Unlike traditional NIP expansion, which adopts a top-down decision-making strategy, China’s free HPV vaccination policy evolved with a distinct bottom-up strategy originating from local pilots, which is demonstrated to be instrumental for national policy-making. The extensive local pilots of free HPV vaccination have served as a powerful engine that drives a rapid and substantial increase in HPV vaccination rate, played a pivotal role in shaping the market of HPV vaccines, and contributed to achieving the economies of scale, which triggered a substantial price reduction. It also fostered a national consensus on the critical role of HPV vaccination in cervical cancer prevention and control, a principle now enshrined in the core public health knowledge repository across the country. A potential strategy to introduce new vaccines into the NIP could be piloting first and expanding incrementally with the bottom-up strategy, leveraging a comprehensive platform under the framework of the national policy, and then making use of the effect of scale and peer pressure, high level engagement, cross-departmental collaboration, and multiple financing mechanisms. Full article

Osteosarcoma (OS) is the most common primary bone cancer in adolescents and young adults. Despite tremendous preclinical and clinical efforts to advance therapy for OS, the standard of care, consisting of surgical resection and pre- and postoperative chemotherapy, has remained unchanged for over 40 years. Growing molecular understanding of OS highlights tumor heterogeneity as a major obstacle to therapeutic advances. In this narrative review, we comprehensively discuss current evidence of OS heterogeneity and strategies to overcome the barrier. Evidence shows that OS heterogeneity is multifactorial: it retains complex and dynamic somatic genomics, including genomic instability, alterations in tumor suppressors, and amplification/overexpression of oncogenes such as MYC. The tumor is associated with various germline vulnerabilities. OS’s tumor microenvironment has intense cellular and spatial diversity, which significantly shapes its heterogeneity. The effects of lineage plasticity, as well as epigenetic and metabolomic mechanisms, on OS heterogeneity are under study. To overcome this extreme heterogeneity, the therapeutic strategies for OS must be comprehensive and diversified. While surgical resection remains a mainstay of treatment, efforts to identify actionable biomarkers that guide risk stratification and therapy are ongoing. Diverse preclinical models offer insights into OS biology and novel therapeutics. To enhance combinational therapy for OS, various agents, including multi-targeted receptor tyrosine kinase inhibitors, immunotherapies, and epigenetic and metabolic modifiers, are being investigated. Distinctive efforts are continuing to establish maintenance therapy for OS. In summary, elucidating the complex drivers of OS heterogeneity, together with the development of multifaceted strategies to address them, is critical to accelerating therapeutic progress in OS. Full article

Gastric cancer remains a major clinical challenge, underscoring the need for more effective drug delivery strategies. Approximately 10–20% of gastric cancers overexpress HER2, conferring aggressive tumor characteristics and poor survival, yet resistance to trastuzumab-based targeted therapy and limited intratumoral antibody penetration continue to restrict clinical outcomes. This study evaluated HER2-targeted exosomes as a delivery platform. Exosomes were engineered to express the p51 peptide, a high-affinity HER2-binding ligand, and loaded with 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a potent HSP90 inhibitor. The cellular uptake and antitumor efficacy of p51-Exo^17-DMAG were assessed in vitro using NCI-N87 and AGS cells and in vivo using a mouse xenograft model. p51-modified exosomes exhibited superior HER2 specific uptake. Treatment with p51-Exo^17-DMAG significantly increased apoptosis, as demonstrated by elevated PARP and caspase3 cleavage, and downregulated oncogenic signaling molecules, including p-AKT, CDK2, VEGF, and c-Myc. Furthermore, p51-Exo^17-DMAG increased the number of TUNEL-positive cells. In the NCI-N87 xenograft model, systemic administration of p51-Exo^17-DMAG significantly inhibited tumor growth without toxicity or histological damage to major organs. Tumor analysis confirmed increased apoptosis and reduced proliferation in vivo. These findings demonstrate that p51-engineered exosomes provide an efficient, selective, and safe platform for HER2-targeted delivery of 17-DMAG, offering a promising precision medicine strategy for HER2-positive gastric cancer. Full article

Mohs Micrographic Surgery (MMS) is considered the most conservative and preserving procedure for removing cutaneous tumors. The major disadvantage of MMS is that tumor involvement in tissue may be underestimated. This may lead to large excisions necessitating complex reconstruction with profound effects on cosmetic results. Some patients refuse complex reconstruction and demand simple closure of post-MMS skin defects. This retrospective cohort study describes our technique of serial Mohs excisions of large non-melanoma skin cancers for patients refusing flaps or skin graft reconstructions. A total of 51 patients who underwent MMS according to the described technique February 2020–May 2021 were included. The mean age was 76.5 (range 63–94) years and 55% were male. More than half of the lesions were on the nose. Mean lesion sizes were 14.25–55 mm depending on location. Most cases required two surgeries and only one needed a third surgery. Postsurgical defects were repaired using primary closure in 90% of cases. Mean follow-up was 31 months (range 6–48) with no evidence of local recurrence. In conclusion, this approach of serial excisions with MMS can be performed safely and achieve better cosmetic outcomes for patients presenting with large skin tumors of the face or other functionally important areas. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with poor outcomes in advanced stages and significant limitations in current chemotherapy regimens due to systemic toxicity. Extracellular vesicles (EVs) have emerged as promising natural drug delivery vehicles, offering the potential for targeted, less toxic therapies. This study investigates the feasibility of using autologous, patient-derived EVs as a delivery system for the chemotherapeutic agent doxorubicin, focusing on how disease stage and the EV protein corona influence loading and delivery efficiency. Methods: EVs were isolated from plasma and tissue samples of CRC patients at different disease stages, as well as from healthy controls, demonstrating successful isolation and characterisation of EVs, with distinct profiles across different sources. Results: Doxorubicin loading into EVs was significantly higher in CRC patient-derived EVs compared to healthy controls, and tissue-derived EVs yielded higher quantities of drug-loaded particles. Delivery of doxorubicin-loaded EVs to recipient CRC cell lines (SW480 and SW620) revealed that disease stage impacts both EV uptake and drug delivery, with late-stage EVs showing reduced uptake and delivery efficiency. The protein corona, known to coat circulating EVs, was found to influence drug loading and delivery. Pre-treatment of cell line-derived EVs with plasma proteins enhanced EV uptake but reduced doxorubicin loading and subsequent delivery, particularly when using plasma from healthy volunteers. Conclusions: These findings underscore the importance of EV source and protein corona composition in optimising drug delivery strategies. Our results suggest that autologous, patient-derived EVs hold potential as a targeted drug delivery system for CRC, but highlight the need for further optimisation of EV isolation, loading methods, and understanding of how disease progression affects EV functionality. This approach could ultimately reduce systemic toxicity and improve therapeutic outcomes for CRC patients. Full article

We aimed to evaluate the impact of malnutrition on post-operative mortality and complications in patients undergoing surgery for ovarian cancer (OC). In this retrospective cohort study utilizing the ACS NSQIP database (2013-2022), all individuals with a diagnosis of OC were included. Patients were classified as having “malnutrition” if they met any of the following: (1) pre-operative albumin level <3.5 g/dL; (2) ≥10% weight loss over 6 months + BMI = 18.5–20 kg/m² in patients <70 years old or BMI = 18.5–22 kg/m² in patients ≥70 years); and (3) BMI < 18.5. Baseline characteristics, 30-day post-operative mortality and complications were compared between “malnutrition” and “no malnutrition” groups. Of the 20,174 included, 8744 (43.3%) had malnutrition and 11,430 (56.7%) had no malnutrition. The malnutrition group had longer total length of hospital-stay (mean days 4.78 vs. 4.17, p < 0.0001), higher rates of venous thromboembolism, and higher cardiac morbidity compared to “no malnutrition”. On univariate analysis, mortality was higher in the “malnutrition” group (0.8% vs. 0.3%, p < 0.0001). This remained significant after adjusting for potential confounders (aOR 2.92, 95% CI 1.92–4.43, p < 0.0001). In conclusion, in patients undergoing surgery for OC, malnutrition increased the risk of post-operative mortality and complications. Malnutrition assessment should be integrated in pre-operative counseling in patients undergoing surgery for OC. Full article

Immune checkpoint inhibitors targeting the PD-1 (Programmed Cell Death Protein 1)/PD-L1 (Programmed Death-Ligand 1) axis have transformed cancer therapeutics, yet their efficacy in gynecologic malignancies particularly high-grade serous ovarian carcinoma remains disappointingly limited. This therapeutic resistance stems from a highly orchestrated, multidimensional immunosuppressive tumor microenvironment (TME) characterized by the convergent actions of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and an inhibitory cytokine network (IL-10, TGF-β, VEGF). Emerging evidence positions TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domain) as a master checkpoint integrator that coordinately regulates CD8+ T-cell exhaustion, NK-cell dysfunction, and Treg-mediated suppression. Dual blockade of PD-1 and TIGIT represents a mechanistically rational strategy to dismantle this immunosuppressive fortress. This review synthesizes current understanding of the gynecologic TME architecture, delineates the molecular and cellular basis for TIGIT/PD-1 synergy, critically evaluates ongoing clinical translation efforts, and proposes an integrative framework leveraging spatial transcriptomics, single-cell resolution immunoprofiling, and patient-derived experimental models to accelerate biomarker-driven therapeutic development. Full article

Background/Objectives: We aimed to evaluate temporal changes in patient selection, surgical practice, and postoperative outcomes of radical prostatectomy in Switzerland (2020–2025) using a national registry. Methods: Data from 7687 patients undergoing radical prostatectomy were extracted from a prospective national registry (January 2020–March 2025). Preoperative, operative, and postoperative variables were compared descriptively using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. Temporal trends were assessed using locally estimated scatterplot smoothing. Multivariable logistic regression analyses were performed for positive surgical margins and PSA persistence. Results: Baseline patient characteristics remained stable over time. The use of MRI-targeted biopsy increased from 46% to 84% (p < 0.001). The proportion of low-risk diseases being treated decreased from 7.1% to 4.0% (p = 0.040). Minimally invasive surgery increased from 81% to 95% (p < 0.001); pelvic lymph node dissection declined from 83% to 63% (p < 0.001). Operative time (205 vs. 185 min, p = 0.002) and blood loss (300 vs. 200 mL, p < 0.001) decreased over time. Lymph node invasion decreased from 11% to 6.0% (p = 0.001), positive surgical margins from 27% to 22% (p = 0.044), and prostate-specific antigen persistence from 18.5% to 11.3% (p = 0.001). Severe postoperative complications decreased from 2.5% to 0.8% (p = 0.014). After multivariable adjustment, surgery performed in 2024 remained independently associated with lower rates of positive surgical margins (OR 0.73, 95% CI 0.57–0.93) and PSA persistence (OR 0.26, 95% CI 0.19–0.37) compared with 2020. Conclusions: Using the Swiss national registry, we demonstrate that radical prostatectomy has evolved toward more risk-adapted patient selection, near-universal minimally invasive surgery, and more selective pelvic lymph node dissection. Despite a shift away from low-risk disease, perioperative and early oncological outcomes improved, likely reflecting a combination of evolving diagnostic pathways, increasing surgical experience, and broader changes in perioperative management. Full article

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

Gadolinium is a rare-earth element that is promising for the field of biomedicine due to its unique properties that enhance image quality, giving it high potential in targeted cancer therapy, antimicrobial treatments, etc. The disadvantage of Gd-containing materials is their high toxicity. In this work, ensembles of Fe and Al₂O₃ nanoparticles were fabricated by the electric explosion of wire and Gd ribbons using rapid quenching techniques. Stable Fe, Fe/Gd and Fe/Gd/Al₂O₃ aqueous suspensions with a Z-potential of about –54 mV were fabricated by the ball-milling mechanosynthesis of Fe (100%), Fe and Gd (70 and 30 wt. % accordingly) and Fe, Al₂O_3, and Gd (69, 30 and 1 wt.% accordingly). Fillers from suspensions were used for the synthesis of epoxy composites mimicking natural tissue with embedded magnetic particles. The concentration range for synthesized epoxy composites (0, 5, 10, and 15 wt.% of the filler) corresponded to the biomedical range of interest. Thin-film magnetoimpedance (MI) elements were prepared by a sputtering technique: conventional [FeNi/Cu]₅/Cu/[Cu/FeNi]₅ (NP) element and [FeNi/Cu]₅/Cu/[Cu/P{FeNi]₅} element with patterned top multilayer (SqP). They showed a maximum MI ratio of about 160% for NP and about 60% for SqP. MI sensor response was affected by the presence of filled magnetic composites in the shape of cylinders (5 mm × 4 mm) situated at about 1 mm due to the stray fields in the filler. MI response showed a linear dependence on the filler concentration for each selected position. These results open the possibility to develop new iron- and gadolinium-containing materials for simultaneous magnetic imaging and detection by magnetic field sensors, extending the functional properties of Fe/Gd materials for biomedical devices and therapies. Full article

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia had consistently worse OS. Compared with patients without lymphopenia, the lymphopenia cohort had lower OS at 6 months (HR 1.29, 95% CI 1.22–1.37), 12 months (HR 1.28, 95% CI 1.21–1.35), 24 months (HR 1.26, 95% CI 1.2–1.33), and, in exploratory analyses with substantial right censoring and limited observed follow-up, 36 months (HR 1.26, 95% CI 1.2–1.33) and 5 years (HR 1.26, 95% CI 1.2–1.33), though these estimates should be considered hypothesis-generating only. At 6 months, baseline lymphopenia was associated with a greater healthcare utilization (RR 1.05, 95% CI 1.02–1.09), a higher infection risk (RR 1.08, 95% CI 1.01–1.15), and similar rates of clinically coded irAEs (RR 1.0, 95% CI 0.93–1.09), an observation subject to competing risk from early mortality in the lymphopenic cohort. Subgroup analysis, stratified by tumor subtypes and prior lines of therapy, showed consistently lower OS in the lymphopenia group, consistent with the primary outcome results. Conclusions: In this large propensity-matched real-world analysis of 10,498 patients with diverse solid tumors, baseline lymphopenia at ICI initiation was associated with persistently inferior OS at 6, 12, and 24 months (primary and secondary endpoints), greater early healthcare utilization, and a higher serious infection risk. Critically, lymphopenic patients developed irAEs at an identical rate to non-lymphopenic patients despite worse survival, a dissociation suggesting that baseline ALC stratifies patients along mortality risk and immune activation capacity as partially independent axes. These findings could support the use of baseline ALC as a simple, universally available biomarker that informs not only survival prognosis but also the anticipated toxicity profile of ICI therapy and highlight the need for competing-risk analyses and prospective immune phenotyping to characterize this relationship fully. Full article

Aberrant expression of multiple microRNAs has been reported in gastric cancer. In particular, microRNA-597 has been associated with poor survival rates but is not yet well characterized. Seventy-five clinical samples, four cell lines, and two patient-derived organoids were evaluated for the expression of microRNA-597 and its target genes. microRNA-597 was transiently transfected for analysis of cell migration, invasion, wound healing, colony formation, and cell viability, and its regulation by long non-coding RNAs was explored using the TCGA-STAD and LncBook tools. In clinical samples, low expression of microRNA-597 was associated with the intestinal subtype (p = 0.002) and stages III and IV (p = 0.048). All functional readouts were reduced after microRNA-597 transfection, including colony formation, in patient-derived organoids. Among target genes, RUNX1 was directly regulated by microRNA-597. Other cell invasion genes were dependent on RUNX1 as a hub for regulation. Analysis of the Intersection between long non-coding RNAs co-expressed with RUNX1 and those with the highest microRNA-597 prediction binding identified KCNQ1OT1 as the top transcript. Silencing of KCNQ1OT1 and co-expression in clinical samples suggest the existence of a KCNQ1OT1/microRNA-597/RUNX1 network. The results indicate that microRNA-597 directly suppresses RUNX1, while KCNQ1OT1 modulates this interaction. Our approach enabled the simultaneous analysis of dysregulation in three families of transcripts in gastric cancer progression. Full article

Background: The association between oral health and gastrointestinal (GI) cancers has been primarily investigated within a periodontitis-centered framework. However, the potential contribution of cumulative oral disease burden, including dental caries and apical pathology, remains insufficiently explored. The Decayed, Missing, and Filled Teeth (DMFT) index reflects lifetime exposure to oral microbial dysbiosis and chronic inflammation. Methods: This retrospective exploratory study included patients with GI cancers referred for perioperative oral screening and management at a tertiary care center between 2015 and 2025. Oral health was evaluated using the DMFT index, periodontal probing depth, and radiographically diagnosed apical periodontitis. Age-stratified DMFT and periodontal parameters were compared with national reference data, while apical periodontitis prevalence was descriptively assessed. Results: Patients with GI cancers demonstrated higher DMFT values than national averages across most adult age groups. The prevalence of periodontal pockets (≥4 mm and ≥6 mm) was also elevated. Apical periodontitis was common, affecting 46.3% of patients, with some age groups exceeding 50%. Overall, these findings indicate oral disease clustering with coexisting chronic oral conditions. Conclusions: Patients with GI cancers exhibit substantial oral disease burden, including increased caries experience, periodontal pathology, and apical lesions. These findings suggest that the oral–gastrointestinal cancer relationship may extend beyond a periodontitis-centered paradigm, and that cumulative oral disease burden—including cariogenic processes—may represent an underrecognized component of this axis. The DMFT index may serve as a surrogate marker of lifelong oral inflammatory exposure. While causal relationships cannot be established, this study provides a basis for future mechanistic and longitudinal investigations. Full article