Search Results (729)

With the global aging population, skeletal muscle aging has threatened to elderly health, making dietary interventions for age-related muscle decline a research priority. Lycium barbarum, a traditional food and medicinal herb, was used in the study to prepare Lycium barbarum water (LBW). This experiment was conducted in animals and included four groups: young control (C-Young), aged control (C-Aged), young LBW-drinking (G-Young), and aged LBW-drinking (G-Aged). Assessments covered skeletal muscle mass, cross-sectional area, and exercise ability to compare health status. The study measured mRNA expression of Atrogin-1 and MuRF-1 from the Forkhead Box O (FOXO) pathway, advanced glycation end products (AGEs) and senescence-associated β-galactosidase (SA-β-gal), oxidative stress levels via superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH), inflammatory levels through interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α), and applied untargeted metabolomics to profile metabolic alterations. Optimal LBW was achieved at 80 °C with a 1:10 (w/v) solid-liquid ratio. In aged mice, long-term LBW administration improved exercise capacity, reduced muscle atrophy, and increased muscle mass, alongside decreased aging-related markers, alleviated oxidative stress, and modulated inflammatory levels. Additionally, metabolomics confirmed age-related oxidative stress and inflammation. Long-term LBW consumption alleviates age-related skeletal muscle dysfunction via multi-target regulation, holding promise as a natural nutritional intervention for mitigating skeletal muscle aging. Full article

Biliary tract cancer (BTC) is a rare and aggressive type of malignancy characterized by heterogeneity both in tumor biology and in the immune microenvironment. Most patients are diagnosed with advanced-stage disease and have limited curative options. Although the introduction of immune-checkpoint inhibitors (ICI) has transformed the treatment landscape for several solid tumors, their effects on BTC remain modest. New combinations have promoted incremental improvements in the survival of patients with advanced BTC, but the complex interplay between immune therapies and the tumor microenvironment continues to be a major challenge to improve therapeutic outcomes. Nonetheless, ongoing studies are investigating combinations that may potentially improve results in this lethal disease. This review provides an overview of the evolving role of ICIs in BTC, discusses the impact of tumor heterogeneity on treatment response, and explores future directions to optimize patient selection. Full article

Phytochemicals exhibit a broad spectrum of pharmacological activities, including significant anticancer potential. However, their clinical translation is often hampered by poor aqueous solubility, low bioavailability, and chemical instability. Lipid-based nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have proven to be effective strategies for addressing these challenges. These nanocarriers improve the solubility, stability, and bioavailability of phytochemical-based anticancer agents, while enabling controlled and tumor-specific drug release. Encapsulation of anticancer phytochemicals such as curcumin, quercetin, resveratrol, silymarin, and naringenin in SLNs and NLCs has demonstrated improved therapeutic efficacy, cellular uptake, and reduced systemic toxicity. Co-delivery strategies, combining multiple phytochemicals or phytochemical–synthetic drug pairs, further contribute to synergistic anticancer effects, dose reduction, and minimized side effects, particularly important in complex cancers such as glioblastoma, breast, and colon cancers. This review presents a comparative overview of SLNs and NLCs in terms of formulation methods, in vitro characterization, and classification of key phytochemicals based on chemical structure and botanical sources. The roles of these lipidic carriers in enhancing anticancer activity, challenges in formulation, and recent patent filings are discussed to highlight ongoing innovations. Additionally, hybrid lipid–polymer nanoparticles are introduced as next-generation carriers combining the benefits of both systems. Future research should aim to develop scalable, biomimetic, and stimuli-responsive nanostructures through advanced surface engineering. Collaborative interdisciplinary efforts and regulatory harmonization are essential to translate these lipid-based carriers into clinically viable platforms for anticancer phytochemical delivery. Full article

Background: EphA2 is a receptor tyrosine kinase that contributes to tumor growth and metastasis and has been identified as a viable target for many solid cancers. Investigating EphA2’s impact on the host immune system may advance our understanding of tumor immune evasion and the consequences of targeting EphA2 on the tumor microenvironment. Methods: Here, we examine how tumor-specific EphA2 affects the activation and infiltration of immune cell populations and the cytokine and chemokine milieu in murine models of non-small cell lung cancer (NSCLC). Results: Although EphA2 overexpression in NSCLC cells did not display proliferative advantage in vitro, it conferred a growth advantage in vivo. Analysis of lung tumor infiltrates via flow cytometry revealed decreased natural killer and T cells in the EphA2-overexpressing tumors, as well as increased myeloid populations, including tumor-associated macrophages (TAMs). T-cell activation, particularly in CD8+ T cells, was decreased, while PD-1 expression was increased. These changes were accompanied by increased monocyte-attracting chemokines, specifically CCL2, CCL7, CCL8, and CCL12, and immunosuppressive proteins TGF-β and arginase 1 in RNA expression analyses. Conclusions: Our studies suggest EphA2 on tumor cells recruits monocytes and promotes their differentiation into TAMs that likely inhibit the activation and infiltration of cytotoxic lymphocytes, promoting tumor immune escape. Full article

Background/Objectives: We aim to identify predictors of response to ICIs in patients with advanced solid tumors that exhibiting a TMB ≥ 10 mut/Mb. Methods: Patients treated with ICIs alone at Northwestern University between 1 January 2015 and 31 December 2020 were identified. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method, and groups were compared using the log-rank test. Wilcoxon rank sum tests, chi-squared tests, and Fisher’s exact tests were used for univariable analyses evaluating the impact of clinical and genetic variables on response, with significance defined as p < 0.05. Results: A total of 117 patients were classified as ICI-sensitive (n = 88) or non-ICI-sensitive (n = 29). Among evaluable patients (n = 105), the overall response rate was 34% with 14% achieving a complete response. Median PFS and OS were 8.05 months and 26.8 months, respectively. Higher PFS rates were significantly linked to the ICI-sensitive tumor group (p = 0.009), absence of liver metastasis (p = 0.015), and no prior systemic treatment (p = 0.001) in both cohorts. In non-ICI-sensitive patients, a TMB of ≥15 mut/Mb correlated with improved outcomes (p = 0.012). Mutations in the MYC pathway (p = 0.03) and the MLL2 gene (p = 0.014) were associated with poorer responses, while mutations in the TERT gene were linked to better responses (p = 0.031). Conclusions: Patients without liver metastasis, mutations in TERT, and TMB ≥ 15 mut/Mb are associated with superior response, while mutations in the MYC pathway and MLL2 are associated with worse responses. Full article

Antrodia cinnamomea, a renowned rare medicinal fungus in China, is rich in active components, exhibiting pharmacological effects, such as liver protection, hypoglycemic activity, and anti-tumor properties. Aiming to address the lack of horizontal comparative studies on volatile components of A. cinnamomea under different culture methods and the limitations of traditional detection methods, this study investigated the mycelia of A. cinnamomea cultured by solid-state culture (SAC), liquid culture (LAC), and dish culture (DAC). The flavor profiles were comprehensively evaluated using a combination of electronic tongue (E-tongue), electronic nose (E-nose), gas chromatography–ion mobility spectrometry (GC-IMS), and multivariate statistical methods. Results from E-tongue and E-nose showed distinct flavor profiles among the three culture methods. A total of 75 volatile compounds were detected by GC-IMS, among which esters, alcohols, and ketones were the main components, accounting for 62.7%. Partial least squares discriminant analysis (PLS-DA) identified 41 characteristic volatile compounds, and cluster heatmaps and orthogonal partial least squares discriminant analysis (OPLS-DA) further validated the metabolic preferences among culture methods. These findings provide a scientific basis for improving A. cinnamomea product quality through targeted flavor enhancement, support the development of standardized functional foods, and establish a flavor fingerprint for authenticity assessment, advancing the high-value utilization of this medicinal fungus. Full article

Recent advances in precision oncology have led to significant breakthroughs through the targeting of defined oncogenic drivers. However, the clinical efficacy of single-target therapies is increasingly constrained by the intrinsic complexity and adaptability of cancer. Solid tumors frequently arise from multifactorial oncogenic processes and adapt via diverse resistance mechanisms, ultimately limiting the durability of monotherapies. This review advocates for a paradigm shift toward multi-targeted, AI-enhanced strategies that harness high-throughput multi-omic data to inform the rational design of combination therapies. By leveraging artificial intelligence for drug discovery and repurposing, response prediction, and clinical trial optimization, the field of oncology is poised to transcend reductionist approaches and more fully address the biological intricacy of cancer. Full article

Background/Objectives: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The BRAF V600E mutation, common in PTC, is linked to aggressive features, and its allele frequency (AF) may serve as a biomarker for tumor aggressiveness. This study explored the association between BRAF V600E AF and aggressive histopathological features in MPTC. Methods: Data from 1 January 2016 to 23 December 2023 were retrieved from two McGill University teaching hospitals. Inclusion criteria comprised patients aged ≥ 18 years with thyroid nodules ≤ 1 cm, documented BRAF V600E mutation and AF results, and available surgical pathology reports. Tumor aggressiveness was defined as the presence of lymph node metastasis, aggressive histological subtype (tall cell, hobnail, columnar, solid/trabecular or diffuse sclerosing), extra thyroidal extension, or extensive lymphovascular extension. Associations were explored using t-tests. Results: Among 1564 records, 34 met the inclusion criteria and were included in analyses. The mean BRAF V600E AF was significantly higher in aggressive tumors (23.58) compared to non-aggressive tumors (13.73) (95% CI: −18.53 to −1.16, p = 0.03). Although not statistically significant, trends were observed for higher BRAF V600E AF in tumors with lymph node metastasis (mean AF: 25.4) compared to those without (mean AF: 16.67, p = 0.08). No significant difference was noted in BRAF V600E AF by histological subtype (mean AF for aggressive: 19.57; non-aggressive: 19.15, p = 0.94). Conclusions: Elevated BRAF V600E AF is associated with aggressive behavior in MPTC, highlighting its potential as a biomarker to inform treatment strategies. Larger studies are warranted to validate these findings and enhance clinical management of MPTC patients. Full article

Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, or a combination of these treatments. Emerging modalities within immunotherapy are anticipated to extend the results with conventional therapy by stimulating the patient’s own intrinsic potential for tumor-specific immunologic rejection. Combination regimens of chemotherapy and tumor-infiltrating lymphocyte (TIL) therapy in advanced colorectal cancer and pancreatic cancer, autologous monocyte therapy in advanced gastric cancer, and CAR-T therapy trained against GI-selective tumor antigens such as carcinoembryonic antigen are currently being studied. Clinical trials are underway to study the combination of various chemotherapeutic agents along with immunotherapy in the management of cholangiocarcinoma, hepatocellular carcinoma, and esophageal cancer. Alternative therapies are needed based on the tumor immune microenvironment, which can lead to a personalized approach to treatment. In this review, we discuss the current status of various modalities of immunotherapy in common GI malignancies, along with their mechanisms of immune activation and cancer suppression. We will also discuss the use of immunotherapy in less common solid GI malignancies and touch on recent advancements and clinical trials. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular profiling has uncovered actionable genomic alterations in select subgroups of PDAC, yet the clinical impact of targeted therapies remains modest. This review aims to provide a clinically oriented synthesis of emerging molecular targets in PDAC, their therapeutic relevance, and practical considerations for biomarker testing, including current FDA and EMA indications. Methods: A narrative review was conducted using data from PubMed, Embase, Scopus, and international guidelines (NCCN, ESMO, ASCO). The selection focused on evidence published between 2020 and 2025, highlighting molecularly defined PDAC subsets and the current status of targeted therapies. Results: Actionable genomic alterations in PDAC include KRAS G12C mutations, BRCA1/2 and PALB2-associated homologous recombination deficiency, MSI-H/dMMR status, and rare gene fusions involving NTRK, RET, and NRG1. While only a minority of patients are eligible for targeted treatments, early-phase trials and real-world data have shown promising results in these subgroups. Testing molecular profiling is increasingly standard in advanced PDAC. Conclusions: Despite the rarity of targetable mutations, systematic molecular profiling is critical in advanced PDAC to guide off-label therapy or clinical trial enrollment. A practical framework for identifying and acting on molecular targets is essential to bridge the gap between precision oncology and clinical management. Full article

Cancer has remained one of the leading causes of death worldwide throughout history despite significant advancements in drug development, radiation therapy, and surgery. Traditional chemotherapeutic small molecules are often hindered by narrow therapeutic indices and limited specificity, leading to suboptimal clinical outcomes. On the other hand, more advanced approaches, such as antibody–drug conjugates (ADCs), frequently encounter obstacles, including poor tumor penetration and prohibitive production costs. The tumor-forming and metastatic capacity of cancer further challenges currently available cancer therapies by creating a biochemical milieu known as the tumor microenvironment (TME). Although solid tumor development presents significant obstacles, it also opens new avenues for innovative therapeutic approaches. It is well-documented that as tumors grow beyond 1–2 mm³ in size, they undergo profound changes in their microenvironment, including alterations in oxygen levels, pH, enzymatic activity, surface antigen expression, and the cellular composition of the stroma. These changes create unique opportunities that can be exploited to develop novel and innovative therapeutics. Currently, numerous ADCs, small-molecule–drug conjugates (SMDCs), and prodrugs are being developed to target specific aspects of these microenvironmental changes. In this review, we explore five TME parameters in detail, with a focus on their relevance to specific cancer types, phenotypic identifiers, and preferred methods of therapeutic targeting. Additionally, we examine the chemical moieties available to target these changes, providing a framework for design strategies that exploit the dynamics of the tumor microenvironment. Full article

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 10⁹ viable TIL cells, with a median yield of 1.1 × 10¹⁰ cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-γ and TNF-α upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC. Full article

The tumor microenvironment (TME) in advanced solid tumors is determined by immune checkpoints (PD-1, CTLA-4, and CD95) and cytokine networks (IL-2, IL-10, and TNF-α) that drive CD8+ T cell exhaustion, metabolic reprogramming, and apoptosis resistance, enabling immune evasion. Some studies revealed PD-1/CD95 co-expression is a marker of T cell dysfunction, while CTLA-4 upregulation correlates with suppressed early T cell activation. IL-10 has emerged as a potential biomarker for chemoresistance and tumor aggressivity, consistent with its role in promoting anti-apoptotic signaling in cancer stem cells (CSCs). Engineered IL-2 variants and TNF-α modulation are highlighted as promising strategies to revitalize exhausted CD8+ T cells and disrupt CSC niches. This prospective single-center study investigated the dynamic TME alterations in 16 patients with immunotherapy-naïve stage IV non-small-cell lung cancer (NSCLC) and metastatic melanoma treated with anti-PD-1 nivolumab. The longitudinal immunophenotyping of peripheral blood lymphocytes (via flow cytometry) and serum cytokine analysis (via ELISA) were performed at the baseline, >3, and >6 months post-treatment to evaluate immune checkpoint co-expression (PD-1/CD95 and CTLA-4/CD8+) and the cytokine profiles (IL-2, IL-10, and TNF-α). Full article

Adoptive cell therapies have transformed the treatment landscape for hematologic malignancies. Yet, translation to solid tumors remains constrained by antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and poor persistence of conventional CAR-T cells. In response, innate immune cell platforms, particularly chimeric antigen receptor–engineered natural killer (CAR-NK) cells and chimeric antigen receptor–macrophages (CAR-MΦ), have emerged as promising alternatives. This review summarizes recent advances in the design and application of CAR-NK and CAR-MΦ therapies for solid tumors. We highlight key innovations, including the use of lineage-specific intracellular signaling domains (e.g., DAP12, 2B4, FcRγ), novel effector constructs (e.g., NKG7-overexpressing CARs, TME-responsive CARs), and scalable induced pluripotent stem cell (iPSC)-derived platforms. Preclinical data support enhanced antitumor activity through mechanisms such as major histocompatibility complex (MHC)-unrestricted cytotoxicity, phagocytosis, trogocytosis, cytokine secretion, and cross-talk with adaptive immunity. Early-phase clinical studies (e.g., CT-0508) demonstrate feasibility and TME remodeling with CAR-MΦ. However, persistent challenges remain, including transient in vivo survival, manufacturing complexity, and risks of off-target inflammation. Emerging combinatorial strategies, such as dual-effector regimens (CAR-NK⁺ CAR-MΦ), cytokine-modulated cross-support, and bispecific or logic-gated CARs, may overcome these barriers and provide more durable, tumor-selective responses. Taken together, CAR-NK and CAR-MΦ platforms are poised to expand the reach of engineered cell therapy into the solid tumor domain. Full article

Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic stratification are still lacking. In recent years, circulating cell-free DNA (cfDNA) has emerged as a promising liquid biopsy tool in several solid tumors, offering insights into tumor burden, heterogeneity, and molecular dynamics. However, its application in oral oncology remains underexplored. This study aims to review and discuss the current evidence on cfDNA quantification and mutation analysis (including TP53, NOTCH1, and EGFR) in patients with OPMDs and OSCC. Particular attention is given to cfDNA fragmentation patterns, methylation signatures, and tumor-specific mutations as prognostic and predictive biomarkers. Moreover, we highlight the challenges in standardizing pre-analytical and analytical workflows in oral cancer patients and explore the potential role of cfDNA in monitoring oral carcinogenesis. Understanding cfDNA dynamics in the oral cavity might offer a novel, minimally invasive strategy to improve early diagnosis, risk assessment, and treatment decision-making in oral oncology. Full article