Search Results (898)

Background: Biological aging influences cancer outcomes, but its changes during chemotherapy and impact on chemotoxicity in colorectal cancer (CRC) remain underinvestigated. We examined (1) trajectories of biological aging (using Levine Phenotypic Age) during six months of chemotherapy, (2) sociodemographic and clinical risk factors for biological aging, and (3) links between biological aging and chemotoxicity. Methods: Using data from electronic health records (2013–2019) from 1129 adult CRC patients, we computed biological aging (raw Levine Phenotypic Age and its age acceleration [Levine Phenotypic Age–chronological age]) from routine blood tests (e.g., complete blood counts, hepatorenal/inflammatory markers). Chemotoxicity was identified primarily via International Classification of Diseases (ICD-9 and -10) codes. Results: Chemotherapy accelerated biological aging over time. Biological aging at baseline and changes over time predicted chemotoxicity. However, changes in biological aging over time showed stronger associations than baseline biological aging. Advanced cancer stages, higher comorbidity burden, and socioeconomic disadvantage (especially area-level deprivation) were associated with accelerated biological aging at baseline and over time. Biological aging occurred across both young and older adults. Conclusions: Levine Phenotypic Age, computed from routine blood tests in EHRs, offers a feasible clinical tool for aging-related chemotoxicity risk stratification. Validation in diverse cohorts and the development of predictive models are needed. Full article

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with an increasing incidence worldwide. Single nucleotide polymorphisms (SNPs) may influence disease risk and serve as predictive markers. This study aimed to evaluate the association of PNPLA3 (rs738409 and rs2294918), GCKR (rs780094), MBOAT7 (rs641738), NCAN (rs2228603), and TM6SF2 (rs58542926) SNPs with the risk of developing HCC in a Mexican population. A case-control study was conducted in unrelated Mexican individuals. Cases were 173 adults with biopsy-confirmed HCC and 346 were healthy controls. Genotyping was performed using TaqMan allelic discrimination assay. Logistic regression was applied to evaluate associations under codominant, dominant, and recessive inheritance models. p-values were corrected using the Bonferroni test (pC). Haplotype and gene–gene interaction were also analyzed. The GG homozygous of rs738409 and rs2294918 of PNPLA3, TT, and TC genotypes of GCKR, as well as the TT genotype of MBOAT7, were associated with a significant increased risk to HCC under different inheritance models (~Two folds in all cases). The genotypes of NCAN and TM6SF2 did not show differences. The haplotype G-G of rs738409 and rs2294918 of PNPLA3 was associated with an increased risk of HCC [OR (95% CI) = 2.2 (1.7–2.9)]. There was a significant gene–gene interaction between PNPLA3 (rs738409), GCKR (rs780094), and MBOAT7 (rs641738) (Cross-validation consistency (CVC): 10/10; Testing accuracy = 0.6084). This study demonstrates for the first time that PNPLA3 (rs738409 and rs2294918), GCKR (rs780094), and MBOAT7 (rs641738) are associated with an increased risk of developing HCC from multiple etiologies in Mexican patients. Full article

(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver cancer, and the response rate of drugs under clinical research is less than 50%. There is an urgent need for biomarkers to evaluate the efficacy of these drugs. (2) Methods: MASLD was induced in mice using a High-Fat diet (HF), Western diet (WD), and Methionine/Choline-Deficient diet (MCD) for 20 weeks (4 weeks for MCD). Liver tissue biopsies were performed, and the treatment effects of saponin and non-saponin feeds were evaluated. Fat accumulation and hepatic inflammation were measured, and mRNA sequencing analysis was conducted. The therapeutic effects were validated using patient-derived liver organoids. (3) Results: The NAFLD Activity Score (NAS) significantly increased in all MASLD models compared with controls. Saponin treatment decreased NAS in the HF and WD groups but not in the MCD group. RNA sequencing and PCA analysis showed that the HF saponin response samples were similar to normal controls. DAVID analysis revealed significant changes in lipid, triglyceride, and fatty acid metabolic processes. qRT-PCR confirmed decreased fibrosis markers in the HF saponin response group, and GSEA analysis showed reduced HAMP1 gene expression. (4) Conclusions: Among the diets, red ginseng was most effective in the HF diet, with significant effects in the saponin-treated group. The therapeutic efficacy was better when HAMP1 expression was increased. Therefore, we propose HAMP1 as a potential exploratory biomarker to assess the saponin response in a preclinical setting. In addition, the reduction of inflammation and hepatic iron accumulation suggests that saponins may exert antioxidant effects through modulation of oxidative stress. Full article

Background: Gastric cancer (GC) is a malignant tumor of the gastrointestinal tract, characterized by high mortality rates and responsible for about one million new cases each year globally. Surgery is the main treatment, but achieving radical resection remains a relevant intraoperative challenge. Fluorescence-guided surgery offers clinicians greater capabilities for real-time detection of tumor nodules and visualization of tumor margins. In this field, the main challenge remains the development of fluorescent dyes that can selectively target tumor tissues. Methods: we examined the expression of the most suitable GC markers, including carcinoembryonic antigen cell adhesion molecule-5 (CEACAM5) and Claudin-4 (CLDN4), in GC cell lines. To further evaluate their expression, we performed immunohistochemistry (IHC) on tumor and healthy tissue samples from 30 GC patients who underwent partial gastrectomy at the Digestive System Surgery Unit, AOU Careggi, Florence. Additionally, we validated anti-CEACAM5 expression on patient-derived organoids. Furthermore, we developed a fluorescent molecule targeting CEACAM5 on the surface of GC cells and assessed its binding properties on patient tissue slices and fragments. Results: in this work, we first identified CEACAM5 as an optimal GC biomarker, and then we developed a fluorescent antibody specific for CEACAM5. We also evaluated its binding specificity for GC cell lines and patient-derived tumor tissue, achieving an optimal ability to discriminate tumor tissue from healthy mucosa. Conclusions: Overall, our results support the development of our fluorescent antibody as a promising tumor-specific imaging agent that, after further in vivo validation, could improve the accuracy of complete tumor resection. Full article

Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. The study aimed to evaluate the prognostic significance of the PTEN and ERG biomarkers in predicting BCR and tumor progression in PCa patients who underwent radical prostatectomy. Methods: This study consisted of a cohort of 91 patients with localized PCa who underwent radical prostatectomy between 2016 and 2022. From this cohort, 77 patients were selected for final analysis. Tissue microarrays (TMAs) were constructed from paraffin blocks, and immunohistochemical (IHC) staining for PTEN and ERG was performed using specific antibodies on the Ventana BenchMark ULTRA system (Roche Diagnostics, Indianapolis, IN, USA). Stained sections were evaluated and correlated with clinical and pathological data. Results: PTEN expression showed a significant negative correlation with BCR (r = −0.301, p = 0.014), indicating that reduced PTEN expression is associated with increased recurrence risk. PTEN was not significantly linked to PSA levels, tumor stage, or lymph node involvement. ERG expression correlated positively with advanced pathological tumor stage (r = 0.315, p = 0.005) but was not associated with BCR or other clinical parameters. Conclusions: PTEN appears to be a valuable prognostic marker for recurrence in PCa, while ERG may indicate tumor progression. These findings support the potential integration of PTEN and ERG into clinical practice to enhance risk stratification and personalized treatment, warranting further validation in larger patient cohorts. Full article

Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article

Background/Objectives: Despite the psychological benefits of breast reconstruction (BR) after mastectomy, uptake remains limited among women with breast cancer. This study explores psychosocial and personality predictors of BR intentions in the pre-mastectomy phase, aiming to inform strategies for mental health promotion in oncology care. Methods: This cross-sectional analysis used preoperative data from a longitudinal study at a university hospital in Greece. Women with primary breast cancer scheduled for mastectomy completed a battery of validated self-report measures, including the International Personality Item Big-Five Factor Markers (IPIP-BFFM), the Hospital Anxiety and Depression Scale (HADS), and the Short Form-36 Health Survey (SF-36). Demographic, clinical, and psychosocial data were also collected. Binary logistic regression was used to examine predictors of (a) BR information-seeking and (b) BR intention. Results: Seventy-four women participated (mean age = 61.1 years). Older age predicted lower BR intention (Exp(b) = 0.897, 95% CI: 0.829–0.970) and information-seeking (Exp(b) = 0.925, 95% CI: 0.859–0.997). Single/divorced status was associated with reduced BR information-seeking (Exp(b) = 0.053, 95% CI: 0.005–0.549). Openness to experience significantly predicted both outcomes (BR information-seeking: Exp(b) = 1.115, 95% CI: 1.028–1.209); BR intention: Exp(b) = 1.095, 95% CI: 1.016–1.181). Higher physical health-related QoL scores were associated with increased BR intention (Exp(b) = 1.039, 95% CI: 1.007–1.072), whereas higher mental health-related QoL (Exp(b) = 0.952, 95% CI: 0.912–0.994) and higher depression scores (Exp(b) = 0.797, 95% CI: 0.638–0.996) were linked to decreased BR intent. No psychological factor significantly predicted information-seeking. Conclusions: These findings underscore the value of psychosocial screening and personality-informed counseling prior to surgery. By identifying individuals less likely to seek information or consider BR, pre-mastectomy assessments can contribute to tailored, mental health-promoting interventions and support informed, patient-centered surgical decision-making. Full article

Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. Magnetic sorting was applied to obtain pure exosomes. Morphology and size were characterized by transmission electron microscopy and nanoparticle tracking analysis. Validation of membrane exosomal markers (CD9, CD63) was performed via Western blotting. MiR-21, miR-31, and miR-133 levels were analyzed in exosomes and parent cells by qPCR. Biological effects of the exosomes were tested by adding them to fibroblast cultures and determining the expression of relevant carcinogenesis markers by qPCR. Exosomes appeared as cup-shaped nano-sized particles, and there was no difference regarding particle diameter and concentration between the three types of exosomes. The oncogenic miR-21 was significantly upregulated both in SCC and SCC-derived exosomes compared to DOK and HaCaT cells and their respective exosomes. However, miR-31 unexpectedly showed the highest expression in normal cells and the lowest in HaCaT exosomes. MiR-133, the tumor suppressor miRNA, was downregulated in both SCC and DOK cells compared to normal (HaCaT) cells, while the opposite situation was observed in exosomes, with HaCaT cells showing the lowest levels of miR-133. The differences in exosome content were reflected in signaling pathway activation in exosome-treated fibroblasts, with SCC exosomes exerting the most potent effect on several cancer-related pathways, notably PIK3/AKT, PTEN, and NOTCH signaling cascades. Full article

Colorectal cancer (CRC) is characterized by complex interactions between inflammation, oxidative stress, and extracellular matrix remodeling. Recent studies have highlighted the significance of the reactive oxygen species (ROS)–nuclear factor kappa B (NF-κB)–matrix metalloproteinase-9 (MMP-9) axis in promoting tumor invasion and metastasis in CRC, linking oxidative stress with inflammatory signaling and extracellular matrix degradation. In this study, we analyzed the concentration of advanced oxidation protein products (AOPPs), expression of NF-κB, and the activity of MMP-9 in tumor tissue, adjacent tissue, and healthy control colon tissue. Tissue specimens were collected from 50 patients with primary CRC following surgical resection. The analyses were performed using appropriate and validated biochemical methods, including ELISA, spectrophotometry, and indirect immunofluorescence. Significantly higher levels of all three markers were observed in tumor tissue compared to controls. Additionally, adjacent tissue exhibited elevated NF-κB expression and MMP-9 activity when compared to healthy colon tissue. AOPP levels correlated strongly with MMP-9 activity, highlighting the role of oxidative stress in the activation of MMP-9. MMP-9 demonstrated the highest predictive value for CRC, emphasizing its potential as a diagnostic and theranostic marker. Our findings support the hypothesis that the ROS–NF-κB–MMP-9 axis plays an important role in CRC progression, particularly during stages T2 and T3. Targeting this pathway may offer new therapeutic strategies for limiting tumor invasion and recurrence. Moreover, ensuring adequate surgical resection margins is crucial to optimizing treatment outcomes. Full article

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article

MET exon 14 skipping mutations have emerged as significant driver alterations in non-small-cell lung cancer (NSCLC), contributing to tumor progression. This study examines the immune microenvironment in NSCLC patients with these mutations and its prognostic implications. We performed multiplex immunofluorescence (mIF) staining on formalin-fixed paraffin-embedded (FFPE) tissue samples from nine NSCLC patients, including four recurrent/metastatic and five non-recurrent/non-metastatic patients. Two panels assessed immune cell markers (CD8, CD4, CD20, CD68, and FoxP3) and immune checkpoints (PD-L1, LAG3, and TIM3). Immune cell infiltration and checkpoint expression were analyzed using HALO^TM software (version 3.6.4134.464). Nearest neighbor analysis was conducted to assess the proximity of immune cells to tumor cells. Univariate Cox regression analysis assessed factors associated with disease-free survival (DFS). CD8+TIM3+ and CD8+LAG3+ cells were predominantly located in the tumor parenchyma of recurrent/metastatic patients but localized to the stroma in non-recurrent/non-metastatic patients. Non-recurrent/non-metastatic patients exhibited a higher density of tertiary lymphoid structures and closer proximity of CD20+ B cells, CD8+TIM3+, and CD8+LAG3+ cells to tumor cells compared to recurrent/metastatic patients, though the differences were not statistically significant. Cox regression analysis suggested a potential association between higher densities of CD8+TIM3+ cells and improved DFS (HR = 0.89), though these findings did not reach statistical significance. Our findings suggest that differences in immune microenvironmental factors, particularly those related to immune checkpoint expression (TIM3 and LAG3), may influence clinical outcomes in NSCLC patients with MET exon 14 skipping mutations. Further studies are needed to validate these observations and explore potential therapeutic implications. Full article

Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited to in vitro models, and its systemic effects remain poorly understood. This study aimed to evaluate the impact of E. tirucalli latex on renal function in healthy Wistar rats. Animals were divided into two groups: a control group receiving water and a treated group receiving E. tirucalli latex (13.47 mg/kg) by gavage for 15 days. Renal function was assessed by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), renal vascular resistance (RVR), and mean arterial pressure (MAP). Additionally, oxidative stress markers, reactive oxygen/nitrogen species, and inflammatory activity were analyzed in renal tissue. E. tirucalli significantly reduced GFR, RPF, and RBF, while increasing RVR and MAP. Renal tissue exhibited elevated levels of advanced oxidation protein products, myeloperoxidase, nitric oxide, and peroxynitrite/hydroxyl radicals. These findings indicate that E. tirucalli latex adversely affects renal hemodynamics and promotes oxidative and inflammatory damage, suggesting potential nephrotoxic effects, even in healthy subjects. Full article

Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods: This study enrolled 680 patients with CRC who underwent curative resection, randomly allocated into a training set (n = 477) and a validation set (n = 203) in a 7:3 ratio. Feature selection was performed using Boruta and Lasso algorithms, identifying nine core prognostic factors through variable intersection. Seven machine learning (ML) models were constructed using the training set, with the optimal predictive model selected based on comprehensive evaluation metrics. An interactive visualization tool was developed to interpret the dynamic impact of key features on individual predictions. The partial dependence plots (PDPs) revealed a potential dose–response relationship between inflammatory–nutritional markers and MLM risk. Results: Among 680 patients with CRC, the cumulative incidence of MLM at 6 months postoperatively was 39.1%. Multimodal feature selection identified nine key predictors, including the N stage, vascular invasion, carcinoembryonic antigen (CEA), systemic immune–inflammation index (SII), albumin–bilirubin index (ALBI), differentiation grade, prognostic nutritional index (PNI), fatty liver, and T stage. The gradient boosting machine (GBM) demonstrated the best overall performance (AUROC: 0.916, sensitivity: 0.772, specificity: 0.871). The generalized additive model (GAM)-fitted SHAP analysis established, for the first time, risk thresholds for four continuous variables (CEA > 8.14 μg/L, PNI < 44.46, SII > 856.36, ALBI > −2.67), confirming their significant association with MLM development. Conclusions: This study developed a GBM model incorporating inflammatory-nutritional biomarkers and clinical features to accurately predict MLM in colorectal cancer. Integrated with dynamic visualization tools, the model enables real-time risk stratification via a freely accessible web calculator, guiding individualized surveillance planning and optimizing clinical decision-making for precision postoperative care. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with limited therapeutic options. This study investigated the expression of HEAT repeat-containing protein 1 (HEATR1) and solute carrier family 27 member 2 (SLC27A2) in ccRCC and their potential as prognostic markers and therapeutic targets. Methods: Analysis of a public proteomic dataset (CPTAC) and immunohistochemistry (IHC) validation in an independent cohort of 52 ccRCC patients was performed. HEATR1 and SLC27A2 expression were correlated with survival outcomes. Reactome pathway analysis was conducted to explore the functional roles of HEATR1 and SLC27A2. Results: The analysis showed that HEATR1 is upregulated and associated with poor prognosis, while SLC27A2 is downregulated and similarly linked to shorter progression-free survival. High HEATR1 expression and low SLC27A2 expression correlated with shorter progression-free survival (PFS) and overall survival (OS) in patients with high-grade ccRCC. Reactome analysis indicated HEATR1’s involvement in RNA metabolism and SLC27A2’s role in lipid metabolism, particularly peroxisomal lipid metabolism and fatty acyl-CoA biosynthesis. HEATR1 exhibited a dual localization in both the cytoplasm and nucleus, while SLC27A2 was primarily observed at the cell membrane and the nucleus. This different subcellular distribution suggests multifaceted roles for both proteins in ccRCC pathogenesis. Conclusions: HEATR1 and SLC27A2 are potential prognostic markers in ccRCC. Further research is needed to validate these findings in larger, more diverse cohorts and elucidate their roles in ccRCC progression. Full article

Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article