Background/Objectives: Whole-blood fatty acid composition provides an objective biomarker of fatty acid status, but its relationships with nutritional characteristics and subsequent quality-of-life (QoL) changes among cancer survivors remain incompletely understood. We aimed to identify whole-blood fatty acid phenotypes and examine their associations with nutritional characteristics, cross-sectional QoL profiles, and subsequent QoL changes in an overlapping longitudinal subcohort. Methods: In this cohort study, the 2023 baseline investigation included 3175 community-dwelling adult cancer survivors with whole-blood fatty acid profiles and paired questionnaires. After excluding participants with substantial missing QoL data, implausible fatty acid measurements, or missing age, sex, or cancer type, 3009 participants comprised the baseline analytical sample. Among these, 423 overlapped with an independent longitudinal cohort contributing QoL data from June 2021 and June 2024, and 398 had complete covariate data for the core adjusted longitudinal analyses. Whole-blood fatty acid phenotypes were identified using principal component analysis and unsupervised clustering. Nutritional characteristics were assessed using habitual dietary intake, Diet Balance Index 2022 scores, and nutrition literacy measures. QoL was assessed using the EORTC QLQ-C30. Multivariable models examined cross-sectional QoL and annualised QoL changes. An open-source phenotype assignment tool was developed to support reproducible classification in future cohorts. Results: Among 3009 baseline participants (mean [SD] age, 64.9 [7.0] years; 2397 women [79.7%]), five whole-blood fatty acid phenotypes were identified. Phenotypes 2 and 3 were rarely observed in the available general-population reference sample and appeared enriched among survivors. Phenotype 2, a high-SFA/low-PUFA phenotype accompanied by higher red meat intake and greater DBI-22 excess scores for red meat and related animal foods, was associated with statistically significant worsening across multiple QoL domains over 12 months despite relatively favourable baseline QoL. Compared with the general-population-mapped reference pool (Phenotypes 1, 4, and 5), Phenotype 2 showed annualised declines in summary score (-4.66 [95% CI, -8.14 to -1.19]) and role functioning (-5.35 [-9.88 to -0.83]), and worsening pain (8.28 [2.58 to 13.98]), dyspnoea (6.83 [0.16 to 13.50]), and constipation (14.10 [7.30 to 20.90]). Prebaseline annualised QoL changes over the preceding 24 months did not differ significantly across phenotypes. Conclusions: Whole-blood fatty acid profiling identified distinct nutritional-metabolic phenotypes among community-dwelling cancer survivors. The high-SFA/low-PUFA phenotype, accompanied by higher red meat intake and greater DBI-22 excess scores for red meat and related animal foods, was associated with worsening across multiple QoL domains over the subsequent 12 months despite relatively favourable baseline QoL. These findings highlight whole-blood fatty acid phenotyping as a potentially informative framework for characterising nutritional-metabolic heterogeneity and subsequent QoL vulnerability among cancer survivors. The open-source phenotype assignment tool may facilitate reproducible phenotype assignment and external validation in future cohorts.

Polyendocrine metabolic ovarian syndrome (PMOS), renamed from polycystic ovary syndrome (PCOS) by global consensus in May 2026, is one of the most common endocrine diseases in women of reproductive age, affecting physical and mental health. Growing evidence suggests that medicine-food homology (MFH) plants and their bioactive compounds may help regulate PMOS-related metabolism and reproductive abnormalities through dietary intervention. This review summarizes their reported roles and potential mechanisms. Based on the existing literature, this review presents nine edible plant resources identified under the MFH/dietary-use framework and 21 bioactive constituents or constituent classes, all selected for detailed synthesis from a broader eligible evidence base and with reported PMOS-related bioactivity. Across preclinical studies, these constituents appear to act through convergent, multi-target mechanisms, including anti-inflammatory and antioxidant activities to reduce systemic inflammation, as well as restoring hormone balance, correcting abnormal lipid metabolism, relieving insulin resistance and protecting ovarian function. Importantly, the evidence base remains predominantly preclinical, with few human randomized trials. Key translational barriers include insufficient standardization of preparations and doses, limited oral bioavailability of several constituents, safety and herb-drug interaction concerns, and uncertain formulation feasibility for functional-food applications. By integrating evidence at the plant and compound levels, this review provides a mechanistic rationale-rather than clinical proof-for further investigation of dietary strategies relevant to PMOS and proposes a framework for the development and evaluation of MFH-based functional foods.

Background/Objectives: Nutritional support may improve the tolerance and effectiveness of definitive treatment in patients with head and neck cancer (HNC). The aim of this study was to investigate the potential clinical deterioration in patients who refuse nutritional consultations and oral nutritional supplementation during chemoradiotherapy (CHRT) for HNC. Methods: The study included 52 patients undergoing CHRT for HNC. Among these patients, 22 (42.3%) received nutritional counseling with oral nutritional supplementation (NCONS), while 30 (57.7%) patients refused NCONS (R-NCONS). The study aimed to investigate and compare the association of NCONS with weight loss, blood parameters, CHRT complications, and overall survival (OS) between the two groups. Results: At the end of CHRT, the R-NCONS group exhibited significantly higher CRP levels (18 mg/L vs. 4 mg/L; p = 0.013) and lower prealbumin levels (0.19 g/L vs. 0.27 g/L; p = 0.003) compared with NCONS group. Furthermore, R-NCONS patients experienced a higher rate of overall complications during CHRT (67% vs. 32%; p = 0.013), required enteral nutrition more frequently (20% vs. 0%; p = 0.033), and exhibited greater weight loss (-11% vs. -5%; p < 0.001). However, the 5-year OS did not differ significantly between the groups. Conclusions: The study demonstrates that while NCONS minimizes overall complications during CHRT, its refusal results in weight loss, elevated CRP and depleted prealbumin levels, and a more frequent need for enteral nutrition interventions.

Cellular senescence (CS) is increasingly recognized as an important cell-state programme involved in breast cancer progression and therapeutic response, but its context-dependent molecular heterogeneity limits its application in prognostic assessment. In this study, GeneCompass-based all-gene in silico perturbation analysis was performed to identify candidate genes predicted to induce senescence or rejuvenation, thereby expanding the known senescence-related gene set. Machine learning further established a seven-gene prognostic signature that may serve as an adjunctive tool for prognostic assessment across multiple cohorts. The time-dependent AUCs at 1, 3, and 5 years were 0.707, 0.700, and 0.684 in the training cohort; 0.657, 0.661, and 0.629 in the test cohort; and 0.611, 0.646, and 0.637 in the external validation cohort, respectively. Single-cell and spatial transcriptomic analyses suggested that the risk component of the prognostic signature reflects not only malignant epithelial cell states but also stromal-vascular remodelling in the tumor microenvironment. Among the signature genes, ADGRF5 exhibited the most pronounced expression alteration, and its knockdown suppressed malignant phenotypes in breast cancer cells. These findings provide an AI-assisted strategy for senescence biomarker discovery and highlight ADGRF5 as a candidate functional risk gene associated with breast cancer progression.

Death-associated protein kinase 1 (DAPK1) is a key regulator of apoptosis and immune responses; however, its prognostic significance in oral cancer remains insufficiently characterized. This study investigated the prognostic relevance of DAPK1 in oral squamous cell carcinoma (OSCC) and examined its associations with immune infiltration and apoptosis-related signaling pathways.

A retrospective translational study design was employed, integrating TCGA-based expression and methylation analyses of 528 head and neck squamous cell carcinoma (HNSCC) tumors, UALCAN epigenetic profiling, GeneMANIA protein-protein interaction mapping, TIMER 2.0 immune correlation analyses in 422 HPV-negative HNSCC patients, and multiplex immunofluorescence validation using a tissue microarray cohort of 82 patients with histologically confirmed OSCC, of whom 75 were eligible for the final analysis at Kaohsiung Veterans General Hospital, Taiwan.

In vitro validation using Western blot analysis in FaDu cells showed that epidermal growth factor receptor (EGFR) inhibition with gefitinib induced upregulation of DAPK1 protein expression at 10 μM and increased total caspase-3 expression. Higher DAPK1 signal in whole-field quantification was associated with increased CD4+ and CD8+ T-cell infiltration and enrichment of apoptosis-related pathways. Patients with high DAPK1 expression demonstrated a consistent protective trend for overall survival in a pre-specified fully adjusted primary model (adjusted HR = 0.51, 95% CI: 0.21-1.21, p = 0.126), and exhibited significantly improved survival in a secondary parsimonious model (adjusted HR = 0.41, 95% CI: 0.18-0.91, p = 0.029). Multiplex immunofluorescence further confirmed stronger DAPK1 and caspase-3 staining, along with denser lymphocytic infiltration within the tumor microenvironment.

Collectively, these findings suggest that DAPK1 is associated with apoptosis-related signaling, increased immune-cell infiltration, and favorable clinical outcomes in OSCC, although its independent prognostic value requires validation in larger cohorts.

Background: In our companion study, the gingival mesenchymal stem cell (GMSC) secretome suppresses oxidative stress and induces apoptosis in primary oral squamous cell carcinoma (OSCC) cells, where those wet-lab results are themselves reported as preliminary; here we ask whether it also engages a proliferation × migration programme in patient tissue. The two arms differ in read-out type (apoptosis and redox there, transcript abundance here), not in opposed function. Methods: Primary OSCC cells received GMSC-conditioned medium (GMSC-CM) or indirect Transwell co-culture, assayed by RT-qPCR (VEGFA, TGFB1, MMP9, CXCL12, CCND1, PCNA, MYC, EGFR), MTT, and scratch-wound migration. Thirteen computational layers plus a GeoMx spatial verify-and-decide layer were applied to public data: TCGA-HNSC, GEO, CPTAC, single-cell inference, prognostic modelling, DepMap and LINCS L1000. Results: All eight transcripts were raised in all three arms (16 of 24 comparisons significant), indicating a pro-tumour transcriptional shift; metabolic activity was unchanged and wound closure was reduced under conditioned medium (p < 0.01). Of 1358 genes significant in all three modalities, 1219 (89.8%, 95% CI 88.0-91.3%) share direction against 25.0% expected by chance (3.59-fold; exact binomial p below machine precision). The pre-registered oral-cavity signature did not validate externally (GSE41613; C = 0.562), and no ligand-receptor pair survived permutation calibration. Conclusions: GMSC paracrine exposure induces a pro-tumour transcriptional programme in primary OSCC cells that replicates at patient level, without demonstrated functional or therapeutic consequence; gefitinib is nominated only as a hypothesis-generating candidate. The evidence rests on three primary cultures (n = 3), one GMSC donor preparation, one 24 h time point, a single reference gene, no cell-line authentication and no test of gefitinib; the study programme has concluded, and these experiments cannot be performed now.

Glioblastoma (GBM) is characterized by extensive neo-angiogenesis, which drives rapid tumor growth and therapeutic resistance. We previously identified PDCD10 as a tumor suppressor in GBM. Here, we investigated whether PDCD10 loss promotes neo-angiogenesis through paracrine signaling and GBM cell plasticity. PDCD10 knockdown (shPDCD10) enhanced endothelial angiogenic activity after treatment with conditioned medium (CM) from shPDCD10 cells and in a direct co-culture model. Moreover, application of CM to the chicken chorioallantoic membrane increased vascular branching in an in vivo angiogenesis model. Antibody array analysis detected elevated levels of multiple pro-angiogenic factors following PDCD10 depletion. In a GBM mouse model, shPDCD10 tumors exhibited pronounced hypervascularity and stromal expansion. Indeed, immunofluorescence revealed colocalization of CD31 with the tumor cell reporter RFP in a subset of implanted shPDCD10 GBM cells, suggesting that these tumor cells acquired an endothelial molecular signature. PDCD10 loss also promoted a glioma stem cell (GSC)-like phenotype, characterized by enhanced clonogenicity, sphere formation, and upregulation of Nestin, KLF4, and SOX2. Under endothelial induction conditions, shPDCD10 sphere-derived cells exhibited endothelial-like characters, showing greater tube-forming capacity and increased Ac-LDL uptake. Taken together, these findings demonstrate that PDCD10 loss promotes GBM neo-angiogenesis involving complementary paracrine and GSC-like plasticity mechanisms, highlighting PDCD10 as a potential therapeutic target to suppress neo-angiogenesis in GBM.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and internal radionuclide therapy is an important locoregional option for unresectable disease. This review summarizes the current landscape of transarterial radionuclide therapy for HCC and, as a translational perspective, considers how the carrier, radionuclide, and dosimetry concepts established in HCC may extend to secondary liver tumors (liver metastases). It begins with established transarterial radioembolization (TARE/selective internal radiation therapy, SIRT) using yttrium-90 (⁹⁰Y) microspheres and the shift toward personalized dosimetry and combination with systemic and immune-based therapies. It then examines alternative radionuclides and carrier systems-including holmium-166 (¹⁶⁶Ho) microspheres, iodine-131 (¹³¹I) lipiodol, rhenium-188 (¹⁸⁸Re) lipiodol, and lutetium-177 emulsified in lipiodol (¹⁷⁷Lu-lipiodol)-from the standpoint of their physical properties, radiochemistry, theranostic potential, and preclinical and clinical evidence. Particular attention is given to ¹⁷⁷Lu-based approaches, including their favorable beta energy, the concurrent imageable gamma emission that enables single-photon emission computed tomography (SPECT)-based dosimetry, and the potential to address post-embolization hypoxia-related radioresistance, while noting that the clinical evidence for ¹⁷⁷Lu-lipiodol remains preclinical. The application of these platforms to colorectal and neuroendocrine liver metastases is then outlined. Finally, regulatory, radiation safety, and waste management considerations and the principal challenges to clinical translation are discussed.

Cutaneous melanoma (CM) and uveal melanoma (UM) derive from melanocytes. Nevertheless, they differ in genetic drivers and progression pathways. Previous research examining the relationship between CM and UM has been constrained by small cohorts and the rarity of UM. The aim of this study was to determine whether UM occurs more frequently in patients with a CM compared to matched patients with keratinocyte carcinoma (KC, squamous or basal cell carcinoma of the skin). Patients with KC were selected as the control to account for the excess risk due to sun exposure and access to healthcare.

We performed a large, multicenter retrospective cohort study using TriNetX, a global health research network and real-world data platform. Cohort 1 had CM or melanoma in situ (MIS) and no history of KC. Cohort 2 had KC and no history of CM or MIS. The main outcome was the incidence of malignant neoplasms of the choroid or ciliary body over a 5-year follow-up, including diagnoses recorded before the index skin cancer. Patients who had metastatic disease were excluded to remove potential misidentifications of choroidal metastasis as UM. A 1:1 propensity score matching (PSM) was used to match demographic and clinical characteristics. Odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding two-sided p-values were used to compare categorical outcomes. Ophthalmologic follow-up was evaluated to rule out surveillance bias.

The CM cohort included 57,352 patients. The KC cohort included 137,083 patients. After PSM each cohort included 52,860 patients. UM occurred in 53 CM patients (0.1%) compared with 13 KC patients (0.02%). This corresponds to an OR of 4.08 (95% CI [2.22, 7.49]; p < 0.001). UM diagnosis preceded CM in 70% of patients with both diagnoses. The association persisted in a sensitivity analysis after excluding patients with UM documented before CM (HR 14.32; 95% CI 7.96-25.76).

Cutaneous melanoma is associated with a significantly higher risk of UM compared to KC. These findings suggest a link between cutaneous and uveal melanoma and may offer a possible role for ophthalmic surveillance in CM patients and dermatology surveillance in UM patients.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies worldwide because of delayed diagnosis, rapid metastatic progression, profound immune suppression, and limited therapeutic responsiveness. The pancreatic tumor microenvironment is characterized by severe hypoxia, stromal desmoplasia, metabolic stress, and oxidative imbalance, all of which contribute to tumor progression and resistance to therapy. Among immune cells involved in antitumor defense, natural killer (NK) cells play an important role through direct cytotoxicity and cytokine production. However, NK-cell activity is frequently impaired in PDAC due to oxidative stress, altered nutrient availability, mitochondrial dysfunction, and dysregulated signaling pathways such as AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR). This review examines current evidence regarding the interactions among redox biology, nutrient sensing, NK-cell metabolism, and pancreatic cancer progression. Importantly, much of the available evidence derives from in vitro studies, animal models, or early-phase clinical investigations, and several findings remain controversial or inconsistent. Further well-designed clinical trials are needed to determine whether nutritional interventions, vitamin supplementation, and strategies targeting metabolic and redox pathways can safely and effectively enhance NK-cell function and improve clinical outcomes in patients with PDAC.