Search Results (21,388)

Background: Structurally active phospholipoproteomic formulations that lack pharmacodynamic targets or systemic absorption present unique challenges for validation. Designed for immune compatibility or structural modulation—rather than therapeutic effect—these platforms cannot be evaluated through conventional clinical or molecular frameworks. Methods: This study introduces a standardized, non-invasive ex vivo protocol using real-time kinetic imaging to document biological behavior under neutral conditions. Eight human tumor-derived adherent cell lines were selected for phenotypic stability and imaging compatibility. Phospholipoproteomic preparations were applied under harmonized conditions, and cellular responses were recorded continuously over 48 h. Results: Key parameters included signal continuity, morphological integrity, and inter-batch reproducibility. The system achieved high technical consistency without labeling, endpoint disruption, or destructive assays. Outputs included full kinetic curves and viability signals across multiple cell–fraction pairings. Conclusions: This method provides a regulatorily compatible foundation for functional documentation in non-pharmacodynamic programs where clinical trials are infeasible. It supports early-stage screening, batch comparability, and audit-ready records within SAP, CTD, or real-world evidence (RWE) ecosystems. By decoupling validation from systemic exposure, the protocol enables scalable, technically grounded decision-making for structurally defined immunobiological platforms. Full article

Chimeric Antigen Receptor (CAR) T cell therapy has achieved high response rates in patients with relapsed or refractory hematologic malignancies. However, comparable efficacy in solid tumors remains limited, partly due to poor CAR T cell persistence and immune-mediated rejection. A major contributor, which has hampered the clinical efficacy of CAR T cells in clinical practice, is the immunogenicity of the murine-derived single-chain variable fragments (scFvs) commonly used in CAR constructs. Cell and humoral immune responses to the murine parts of CARs have been implicated in CAR T cell rejection. Here, we describe the generation and in vitro characterization of humanized CAR T cells targeting prostate-specific membrane antigen (PSMA) on prostate cancer cells, based on two distinct murine scFvs (A5 and D7). Humanization improved the germinality index and successfully preserved CAR surface expression. Functional assays demonstrated that humanized PSMA-CAR T cells retained antigen-specific binding, activation and cytotoxicity, differentiation, exhaustion and cytokine secretion profiles comparable to their murine counterparts. These results support the feasibility of humanization as a strategy to reduce immunogenicity without compromising CAR T cell capabilities, providing a foundation for further in vivo validation in solid tumor settings. Full article

Background/Objectives: Biliary tract cancers (BTCs), encompassing tumors of the bile ducts, gallbladder, or ampulla of Vater, are notoriously hard to manage, especially when surgery is off the table and standard chemotherapy provides only modest benefits. While emerging treatments such as immune checkpoint inhibitors have shown promise, mixed clinical trial results and varied study endpoints have left their true impact unclear. This concise review consolidates current evidence on combining chemotherapy with immunotherapy to clarify whether these regimens can significantly improve outcomes and steer more effective treatment strategies for BTCs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) and prospective comparative studies published from January 2010 to December 2024. Fixed-effect meta-analyses (inverse-variance method) were used as the primary approach, with random-effects models (REML) performed as sensitivity analyses to confirm robustness were performed to calculate pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). Leave-one-out sensitivity analyses and Egger’s tests assessed result stability and publication bias. The review was conducted in accordance with PRISMA 2020 guidelines and registered in OSF. Results: Two RCTs (n = 1754; chemoimmunotherapy n = 874, chemotherapy n = 880) were included in the quantitative meta-analysis. Compared to chemotherapy alone, chemoimmunotherapy significantly reduced the risk of death by 20% (OS, HR = 0.80; 95% CI 0.72–0.89; I² = 0%) and the risk of disease progression or death by 19% (PFS, HR = 0.81; 95% CI 0.73–0.90; I² = 33.5%). Leave-one-out sensitivity analyses confirmed result stability. Egger’s tests showed no significant publication bias (OS p = 0.30; PFS p = 0.40). Two additional studies (IMbrave 151 and Monge 2022) lacking comparative survival data were qualitatively assessed. Conclusions: Chemoimmunotherapy significantly improves OS and PFS compared with chemotherapy alone in advanced BTC, with consistent findings across included trials. These results support the incorporation of chemoimmunotherapy as a first-line therapeutic strategy. Future research should prioritize biomarker-driven patient selection, evaluation of long-term clinical outcomes, and integration of targeted therapies with chemoimmunotherapy. Full article

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer-related death. Hyperactivation of oncogenes and suppression of tumor suppressor genes/proteins drive HCC initiation and progression. MicroRNAs (miRNAs) critically modulate HCC biology by regulating proliferation, apoptosis, and metastasis. Acting either as tumor suppressors or oncomiRs, they shape core signaling pathways, including PI3K/Akt/mTOR, Hippo–YAP/TAZ, Wnt/β-catenin, RAS/MAPK, and p53. Their dysregulation in tissues and body fluids renders them promising diagnostic biomarkers and therapeutic targets. Preclinical studies demonstrate that miRNA-based strategies—either restoring tumor-suppressive miRNAs (e.g., miR-34a, miR-125a-5p) or inhibiting oncogenic miRNAs (e.g., miR-660-5p)—can suppress HCC progression and reduce treatment resistance. Combination approaches, such as pairing miR-122 mimics with miR-221 inhibitors or delivering miR-326 via nanoparticles, further enhance efficacy by simultaneously targeting multiple oncogenic pathways. This review summarizes recent advances in miRNA-mediated regulation of HCC signaling and highlights their clinical potential, including ongoing trials of miRNA-based diagnostics and therapeutics for early detection, prognostication, and personalized treatment. Full article

Introduction: Plant-based phospholipid (PP) liposomes are sustainable, biocompatible, and biodegradable carriers with advantages over synthetic and animal-derived lipids, including lower immunogenic risk and abundant availability from sources such as soy, sunflower, and canola. This systematic review examines their characteristics, innovations, and applications in breast cancer (BCA) therapy. Methods: A total of 43 studies published between 2010 and June 2025 were identified from MEDLINE, Scopus, and Web of Science, focusing on PP composition, drug delivery mechanisms, and therapeutic efficacy in in vitro, in vivo, and preclinical BCA models. Results: Advances include nanotechnology and ligand-targeted systems that improve stability, control drug release, and enhance tumor-specific uptake. PP liposomes co-loaded with chemotherapeutics showed synergistic anticancer effects, increased tumor accumulation, and reduced systemic toxicity. Personalized targeting strategies further improved therapeutic precision and minimized off-target effects. Conclusions: PP liposomes offer an innovative and environmentally sustainable approach for BCA treatment with demonstrated preclinical benefits in efficacy and safety. Translation to clinical practice requires standardized characterization, scalable production, and well-designed trials to confirm safety, dosing, and long-term effectiveness. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune disease that, beyond joint destruction, contributes to neuropsychiatric symptoms such as depression, anxiety, and cognitive impairment. These symptoms are often underrecognized despite their major impact on quality of life. Accumulating evidence suggests that pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), play a key role in this neuroimmune interface. This narrative review examined 16 clinical studies evaluating the effects of biologic therapies targeting TNF-α and IL-6 on mental health outcomes in RA. The total study population comprised 9939 patients, including 2467 treated with TNF-α inhibitors and 7472 with IL-6 or IL-6 receptor inhibitors. TNF-α inhibitors were associated with improved depressive symptoms and emotional well-being. IL-6 inhibitors demonstrated similar psychiatric benefits, particularly in patients with elevated IL-6 levels. The findings highlight that biological therapies in RA may influence not only physical symptoms but also mental health, likely through modulation of neuroimmune pathways including blood–brain barrier permeability, microglial activation, and HPA axis regulation. Future research is needed to clarify these effects in populations stratified by psychiatric comorbidity and inflammatory biomarkers. Clinical implications: Incorporating psychiatric symptom screening and considering neuroinflammatory profiles may help guide the selection of biologic therapy in RA, particularly in patients with comorbid depression or fatigue. Full article

Cancer remains a leading global health challenge, with conventional diagnostic and treatment methods often lacking precision and adaptability. This review explores transformative advancements that are reshaping oncology by addressing these limitations. It begins with an overview of cancer’s complexity, emphasizing the shortcomings of conventional tools such as imaging and chemotherapy, which frequently fail to deliver targeted care. The discussion then shifts to biomarkers, which represent a groundbreaking frontier in early detection, enabling the identification of unique biological signatures that signal the presence of cancer with heightened sensitivity. Building on this foundation, the review examines personalized molecular therapies, which target the specific genetic and molecular vulnerabilities of tumors. These therapies not only enhance treatment efficacy but also minimize adverse effects, offering patients improved outcomes and quality of life. By integrating biomarker-driven diagnostics with tailored therapeutic strategies, a new paradigm of precision oncology emerges, bridging the gap between early detection and effective intervention. Real-world case studies highlight both successes, such as significantly improved survival rates, and persistent challenges, including accessibility and cost barriers. Looking ahead, the review outlines pathways by which to scale these innovations, emphasizing the critical need for robust infrastructure, sustained research investment, and equitable healthcare policies. It concludes by envisioning a future where biomarkers and personalized therapies converge to redefine cancer care, offering earlier detection, precise interventions, and better patient experiences. This work underscores the urgency of adopting cutting-edge approaches to overcome cancer’s persistent threats, paving the way for a more effective and humane era in oncology. Full article

Objective: Microwave hyperthermia is a clinically validated adjunctive therapy in oncology, employing antenna applicators to selectively raise tumor tissue temperature to 40–44 °C. For deep-seated tumors, especially those in anatomically complex areas like the head and neck (H&N) region, phased array antennas are typically employed. Determining optimal antenna feeding coefficients is crucial to maximize the specific absorption rate (SAR) within the tumor and minimize hotspots in healthy tissues. Conventionally, this optimization relies on meta-heuristic global algorithms such as particle swarm optimization (PSO). Methods: In this study, we consider a deterministic alternative to PSO in microwave hyperthermia SAR-based optimization, which is based on the Alternating Projections Algorithm (APA). This method iteratively projects the electric field distribution onto a set of constraints to shape the power deposition within a predefined mask, enforcing SAR focusing within the tumor while actively suppressing deposition in healthy tissues. To address the challenge of selecting appropriate power levels, we introduce an adaptive power threshold search mechanism using a properly defined quality parameter, which quantifies the excess of deposited power in healthy tissues. Results: The proposed method is validated on both a simplified numerical testbed and a realistic anatomical phantom. Results demonstrate that the proposed method achieves heating quality comparable to PSO in terms of tumor targeting, while significantly improving hotspot suppression. Conclusions: The proposed APA framework offers a fast and effective deterministic alternative to meta-heuristic methods, enabling SAR-based optimization in microwave hyperthermia with improved tumor targeting and enhanced suppression of hotspots in healthy tissue. Full article

Objective: This systematic review aimed to investigate existing evidence regarding the implications of the microbiome in the initiation and progression of oropharyngeal squamous cell carcinoma (OPSCC). Methods: PubMed, Scopus, and Cochrane Library systematic searches were conducted according to the PRISMA statements to identify the relevant studies examining microbiome signatures, underlying molecular mechanisms, and their associations with clinical and oncological outcomes in OPSCC. The bias analysis was conducted with the MINORS. Results: Of the 83 identified papers, 12 met the inclusion criteria (298 OPSCC patients). Spirochaetes and most Bacteroidetes may be predominant in OPSCC versus control specimens, while Proteobacteria may be predominant in control tissues compared to tumor. Leptotrichia, Selenomonas, and Treponema trended to be overrepresented in OPSCC compared to control specimens. Neisseria, Porphyromonas, Rothia, Streptococcus, and Veillonela were predominantly reported in normal compared to OPSCC patient specimens. Microbiome compositional shifts were associated with chemoradiation response, HPV status, and addictions. Methodological heterogeneity was noted in sampling protocols, control selection, and analytical approaches, with limited statistical power due to small cohort sizes. Conclusions: OPSCC demonstrates different microbiome signatures from healthy tissues, influenced by HPV status and addictions. A microbiome shift is plausible from pre- to post-chemoradiotherapy, with the baseline microbiome acting as a predictive response factor; however, the low number of studies and substantial methodological heterogeneity across investigations limit the drawing of valid conclusions. The identification of key species is important in the development of OPSCC for developing personalized medicine considering bacterial mediators in terms of prevention, and targeted therapy using the microbiome–tumor–host interaction pathways. Full article

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients. Full article

Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer therapy by reactivating immune surveillance mechanisms against tumor cells. In the context of oral squamous cell carcinoma (OSCC) and broader head and neck squamous cell carcinoma (HNSCC), agents such as pembrolizumab, durvalumab, and ipilimumab target PD-1, PD-L1, and CTLA-4, respectively. This review comprehensively examines their clinical efficacy, safety profiles, mechanisms of action, and therapeutic potential in OSCC management, with an emphasis on strategies to overcome therapeutic resistance. A systematic analysis of the literature was conducted, focusing on clinical outcomes, ongoing trials, and emerging combination therapies. Pembrolizumab has demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) in OSCC patients. Durvalumab, mainly utilized in locally advanced or recurrent disease, has shown survival benefit, particularly in combination or maintenance settings. Ipilimumab exhibits durable responses in advanced OSCC, with enhanced efficacy observed when used alongside nivolumab in dual checkpoint blockade regimens. Although both pembrolizumab and nivolumab target PD-1, they differ in clinical indications and regulatory approvals. Notably, ICIs are associated with immune-related adverse events (irAEs), requiring careful monitoring. Collectively, these agents represent promising therapeutic options in oral cancer, though future studies must prioritize the identification of predictive biomarkers and the development of optimized combination strategies to maximize therapeutic benefit while minimizing toxicity. Full article

KRAS is the most frequently mutated oncogene in cancer. Its activating mutations are associated with aggressive tumor behavior and resistance to certain therapies, including anti-EGFR treatments in colorectal cancer. In particular, the KRAS G12C mutation, which accounts for approximately 3–4% of colorectal cancers (CRCs) and 12–14% of non-small cell lung cancers (NSCLCs), involves a cysteine substitution at codon 12. This has provided the opportunity to develop selective covalent inhibitors that trap the mutant protein in its inactive state. The first targeted therapies for KRAS G12C-mutant cancers comprise sotorasib and adagrasib, both of which have been authorized for use in patients with previously treated NSCLC and CRC. Nevertheless, despite the evidence of clinical activity for this class of agents, primary and acquired resistance, dose optimization, and toxicity management remain significant open challenges. In this review, we summarize recent advances in KRASG12C tumor biology and pharmacological targeting. We also provide additional insights to guide future efforts to overcome the limitations of the current approaches and implement the treatment of KRASG12C-mutant cancers. Full article

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article

Background: Lung cancer is a prevalent malignancy globally, with non-small cell lung cancer (NSCLC) accounting for 80–85% of cases. Solalyraine A1 (SA1) is a steroidal glycoalkaloid derived from Solanum lyratum. However, the effect and mechanism of SA1 on NSCLC remain unclear. Methods: The exosomes from SA1-treated A549 cells were prepared and administered to A549 xenograft mice. Proteomics analysis of SA1-treated A549 cells and their exosomes was conducted to assess the mechanism. Bioinformatics analysis was utilized to identify differentially expressed proteins (DEPs) and key signaling pathways. Western blot analysis confirmed the expression of potential targets. Results: SA1 effectively suppressed tumor growth in A549 xenografts, demonstrating a remarkable inhibition rate of 70.48%. A total of 1154 DEPs were identified in A549 cells, primarily associated with the ribosome pathway. Additionally, 746 DEPs were identified in exosomes, mainly involved in the spliceosome pathway. Five highly regulated DEPs were selected for verification. SA1 was found to suppress MUC5B and elevate APOB expression in A549 cells, while inhibiting MFGM, ANGL4 and increasing GCN1 expression in exosomes. Conclusions: This study demonstrates that SA1 exhibits anti-NSCLC effects by regulating exosome function and related protein expression, providing novel insights for NSCLC treatment. Full article

Eph receptor B2 (EphB2) overexpression is associated with poor clinical outcomes in various tumors. EphB2 is involved in malignant tumor progression through the promotion of invasiveness and metastasis. Genetic and transcriptome analyses implicated that EphB2 is a therapeutic target for specific tumor types. A monoclonal antibody (mAb) is one of the essential therapeutic strategies for EphB2-positive tumors. We previously developed an anti-EphB2 mAb, Eb₂Mab-12 (IgG₁, kappa), by immunizing mice with EphB2-overexpressed glioblastoma. Eb₂Mab-12 specifically reacted with the EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and some cancer cell lines in flow cytometry. In this study, we engineered Eb₂Mab-12 into a mouse IgG_2a type (Eb₂Mab-12-mG_2a) and a human IgG₁-type (Eb₂Mab-12-hG₁) mAb. Eb₂Mab-12-mG_2a and Eb₂Mab-12-hG₁ retained the reactivity to EphB2-positive cells and exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in the presence of effector cells and complements, respectively. In CHO/EphB2, triple-negative breast cancer, and lung mesothelioma xenograft models, both Eb₂Mab-12-mG_2a and Eb₂Mab-12-hG₁ exhibited potent antitumor efficacy. These results indicated that Eb₂Mab-12-derived mAbs could be applied to mAb-based therapy against EphB2-positive tumors. Full article