Search Results (11,575)

Melanoma is an aggressive skin cancer that has the potential to metastasize to the lymph nodes, lungs, liver, and brain. Therefore, the prevention and treatment of this condition are essential for achieving lower incidence rates and improving patient outcomes. Traditional treatment methods like surgery, radiation therapy, and chemotherapy have shown limited efficacy in the treatment of metastatic melanoma, and hence new treatment strategies have been developed. These recently developed treatment options include combining targeted therapies with immunotherapies to reduce drug resistance and improve overall effectiveness in preventing melanoma progression. Moreover, BRAF mutations are found in approximately 40–50% of cutaneous melanomas, and NRAS mutations in 15–25%, making these the two most common oncogenic drivers in the MAPK pathway. While alterations in other genes such as KRAS (~1.7%), HRAS (~1%), and MET (~2–4%) are relatively rare in melanoma, they still remain important to disease biology and are under investigation as potential therapeutic targets. These alterations may contribute to tumor progression, metastasis, and therapeutic resistance, highlighting the importance of continued investigation of targeted strategies in melanoma. This review aims to explore the role of each of these genes in melanoma, discusses their resistance mechanism, and summarizes preclinical and clinical trials involving drug combinations. By integrating current evidence on melanoma-associated genomic alterations with available targeted and immune approaches, this review aims to define molecular and clinical contexts that suggest potential treatment selections for melanoma patients. Full article

There is a growing interest in preventive and complementary therapies to support health, increase the effectiveness of conventional medical treatments, and improve quality of life (QoL). This review summarizes the effects of β-glucans, triterpenes and nucleoside analogs of edible and/or medicinal mushrooms with results of clinical trials that investigated these effects in diabetes, breast-, prostate-, lung- and colorectal cancer patients. The results support that these components effectively alleviate symptoms and improve quality of life of these patients. Higher than 3 g of mushrooms, or equivalent extracts, per day are able to diminish metabolic parameters associated with diabetes, i.e., hyperglycemia, hyperlipidemia, and inflammation. The found survival benefit of mushrooms in breast cancer patients was subgroup- or marker-specific. Additionally, their immunomodulatory effects were more complex—different immunological parameters could be either activated or suppressed by different amounts. Data are limited for prostate cancer patients to date, but lentinan intake may increase the survival time of these patients. The survival of lung cancer patients is significantly improved with the use of beta-glucan as complementary therapy. However, its immunomodulatory role was not confirmed. The application of these mushroom components in patients with colorectal cancer may improve QoL. However, survival benefits are inconsistent across different clinical trials of these patients. In summary, although further randomized clinical trials are still required to evaluate optimal dosage and long-term mechanisms of actions in humans, edible and medicinal mushrooms may serve as valuable tools in preventive or in complementary therapies beside the conventional medical treatments of diabetes and cancer. Full article

Objectives: Cancer patients frequently require long-term central venous catheters to facilitate chemotherapy administration. However, catheter-related thrombosis represents a clinically relevant complication that may interrupt cancer treatment. The role of pharmacological thromboprophylaxis in preventing catheter-related thrombosis remains controversial due to concerns regarding bleeding risk. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of prophylactic anticoagulation for the prevention of catheter-related thrombosis in adult cancer patients with long-term central venous catheters. Methods: A systematic search of PubMed, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov was conducted. Randomized controlled trials and observational studies evaluating prophylactic anticoagulation in adult cancer patients with long-term central venous catheters were included. The primary outcomes were catheter-related thrombosis and major bleeding. Risk of bias was assessed using RoB 2 and ROBINS-I. Meta-analyses were performed using random-effects models where feasible. Results: Sixteen studies were included in this systematic review. Separate quantitative syntheses were performed for randomized and non-randomized studies. In the meta-analysis of three randomized controlled trials including 1022 patients, prophylactic low-molecular-weight heparin did not significantly reduce the risk of catheter-related thrombosis compared with control (RR 0.77; 95% CI 0.53–1.12). A separate analysis of two non-randomized studies including 593 patients suggested a lower reported incidence of catheter-related thrombosis with rivaroxaban (RR 0.23; 95% CI 0.11–0.48). Major bleeding outcomes were inconsistently reported across studies and could not be quantitatively synthesized. Conclusions: Current evidence does not support routine prophylactic anticoagulation for all cancer patients with long-term central venous catheters. However, selected high-risk patients may potentially benefit from individualized thromboprophylaxis. The available evidence remains limited by heterogeneity, low certainty and inconsistent reporting of bleeding outcomes. Further adequately powered randomized trials are required. Full article

Vitamin C (L-ascorbic acid) is an essential micronutrient involved in collagen biosynthesis, redox regulation, immune function, endothelial biology, carnitine synthesis, neurotransmitter metabolism, and non-heme iron absorption. Dietary reference values are designed primarily to prevent deficiency in general populations, but vulnerability to low-vitamin C status may increase during trauma, surgery, chronic inflammation, malignancy, metabolic disease, smoking, poor intake, environmental exposure, and tissue repair. This narrative review synthesizes mechanistic, pharmacokinetic, clinical, and safety evidence on vitamin C as a stress-responsive micronutrient. Evidence is reviewed across tissue repair and wound healing, orthopedic recovery and selected complex regional pain syndrome risk contexts, fatigue, neuropsychiatric vulnerability, cancer-supportive care, vascular homeostasis, dermatologic biology, and preliminary microbiota–gut–brain axis hypotheses. The strength of evidence differs substantially across domains: biochemical functions and deficiency correction are well established, whereas benefits of supraphysiologic oral supplementation in vitamin C-replete patients remain uncertain. Oral nutritional supplementation is distinguished from intravenous pharmacologic ascorbate, with attention to route, formulation, dose division, gastrointestinal tolerance-limited adjustment, and safety monitoring. Because evidence for high-dose oral supplementation remains limited and condition-specific, such use should be individualized, time-limited, and clinician-monitored rather than presented as a population-level recommendation or evidence-defined therapeutic target. Taken together, the clinical value of vitamin C depends on baseline status, patient vulnerability, route, formulation, dosing interval, clinical endpoint, and safety review. Full article

The holobiont represents a fundamental concept in modern biology, defining the organism as a complex unit composed of the host and its symbionts (microbes, viruses) that live together, forming an integrated biological system in which the host and microbes collaborate and influence each other (genetically and metabolically) and evolve as a single entity, rather than the host evolving in isolation. It is recognized that the health and functioning of the host fundamentally depend on its microbiome, consolidating the entire assembly as a unit of evolutionary selection with a shared genome called the hologenome. The oral microbiota plays an essential role in maintaining homeostasis and in modulating epigenetic processes, having unique characteristics due to the oral environment and microbial diversity. The aim of this narrative review is to explore how the oral microbiota interacts with host cells through microbial metabolites, including short-chain fatty acids (SCFAs), microRNAs (miRNAs), extracellular vesicles, and cellular signaling pathways, influencing prenatal and perinatal development as well as overall health. By critically integrating current evidence, this narrative review provides an updated conceptual framework linking the oral microbiota, the holobiont concept, epigenetic regulation, and prenatal and postnatal life. It advances the interpretation of the current literature by bringing together molecular, immunological, and developmental mechanisms that are commonly discussed separately, highlighting the oral microbiota as an active epigenetic regulator within the human holobiont. The effects of oral dysbiosis on both local and systemic health are analyzed, including inflammatory responses, periodontal health, and the risk of chronic diseases or cancer. In addition, the importance of maintaining microbiome homeostasis starting from the gestational period is discussed, in order to prevent epigenetic disturbances that may affect fetal development and postnatal oral health. Collectively, the available evidence supports the biological relevance of the oral holobiont in health and disease while highlighting its potential clinical implications. However, further mechanistic and longitudinal studies are needed to validate these associations and to clarify the causal pathway underlying host–microbiota interactions. Full article

Cancer development arises from dynamic interactions between inherited susceptibility and modifiable environmental exposures, among which diet plays a central role. Carotenoids, lipophilic plant-derived pigments including lycopene, α-carotene, and β-carotene, and retinoids, the vitamin A derivatives that regulate gene transcription via retinoic acid receptors (RARs) and retinoid X receptors (RXRs), have been extensively investigated for their chemopreventive and therapeutic potential. This review aims to provide an integrated, mechanism-based synthesis of the roles of lycopene, α- and β-carotene, and retinoids in cancer chemoprevention and to clarify the conditions under which they are most likely to be effective. Beyond summarizing established antioxidant and nuclear-receptor mechanisms, we highlight as a novel emphasis the epigenetic actions of these compounds, including effects on DNA methylation, histone modification, and microRNA regulation, and we integrate these with the well-recognized divergence between dietary and high-dose supplement outcomes. Experimental evidence demonstrates that carotenoids modulate oxidative stress, inflammation, proliferation, apoptosis, angiogenesis, and metastasis through pathways such as Nrf2/ARE, NF-κB, STAT3, Akt/mTOR, MAPK, and Wnt/β-catenin. Lycopene, in particular, exhibits strong antioxidant capacity and multi-target signaling effects, while provitamin A carotenoids additionally influence retinoid-mediated transcriptional programs. Retinoids exert broader differentiation-inducing and antiproliferative effects through direct nuclear receptor signaling and represent one of the few successful differentiation therapies in oncology, most notably in acute promyelocytic leukemia. Epidemiologic studies generally associate higher dietary carotenoid intake with reduced risk of several malignancies, including prostate, breast, lung, colorectal, and gastric cancers. However, randomized trials of isolated high-dose supplementation, particularly β-carotene in smokers, have demonstrated null or harmful effects, highlighting a critical divergence between whole-food dietary patterns and pharmacologic supplementation. In conclusion, carotenoids and retinoids possess biologically plausible anticancer properties, yet their clinical utility remains context dependent. Future research should prioritize biomarker-guided, precision-based strategies, standardized formulations, and whole-food dietary approaches to clarify their role in cancer prevention and treatment. Full article

Background: Colorectal cancer (CRC), a leading cause of cancer-related mortality worldwide, necessitates improved non-invasive diagnostic and monitoring tools. Circulating tumor cells (CTCs), as intact cellular biomarkers in liquid biopsies, offer valuable morphological and genetic information and hold significant clinical potential for early detection, prognosis, therapy monitoring, and drug development. Bio-ferrography is a non-invasive immunomagnetic separation technique that isolates magnetically labeled entities from fluid samples onto a glass substrate via a focused external magnetic field. Methods: This study employs, for the first time, bio-ferrography for isolation, counting, and microscopic characterization of circulating tumor cells (CTCs) expressing the human epidermal growth factor receptor (EGFR) from blood biopsies taken from patients in the hospital. Magnetic beads conjugated with anti-EGFR antibodies were used to selectively capture CTCs from peripheral blood samples of patients with metastatic CRC and other epithelial malignancies. The method enabled both enumeration and microscopic characterization of isolated cells. Results: Preliminary clinical results demonstrate that bio-ferrography achieves a sensitivity of 90% in stage-IV patients and exhibits higher true positive detection rates compared to conventional tumor biomarkers, including carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA). Conclusions: These findings highlight the potential of bio-ferrography as a robust platform for CTC isolation and analysis. Full article

Background/Objectives: This study was conducted to determine the effect of a Health Belief Model–based education program implemented in Family Health Centers on women’s cervical cancer knowledge and their attitudes and beliefs toward HPV vaccination. Methods: This quasi-experimental pretest–posttest control group study was conducted between March and May 2026 at the Tuşba Training Family Health Center in Van, eastern Türkiye. The study included 150 women aged 18–49 years who had adolescent daughters aged 10–18 years. Data were collected using the Descriptive Information Form, the Cervical Cancer Knowledge Scale, and the Carolina HPV Immunization Attitudes and Beliefs Scale. The intervention group received a structured education program based on the Health Belief Model focusing on cervical cancer, HPV infection, and HPV vaccination. Descriptive statistics, chi-square tests, independent samples t-tests, paired samples t-tests, and mixed-design analysis of variance (ANOVA) were used for data analysis. Results: Following the educational intervention, cervical cancer knowledge scores increased from 2.13 ± 0.79 to 7.24 ± 0.84 in the intervention group, whereas no significant change was observed in the control group (p < 0.001). Total CHIAS scores increased from 24.32 ± 5.30 to 41.23 ± 2.51, accompanied by significant improvements in HPV vaccination attitudes and beliefs (p < 0.001). Significant Group × Time interaction effects were observed for cervical cancer knowledge, total CHIAS scores, and all CHIAS subdimensions (p < 0.001). Conclusions: The findings indicated that the Health Belief Model–based education program was associated with improved knowledge about cervical cancer and HPV and with more favorable attitudes and beliefs toward HPV vaccination. Structured educational programs implemented in primary healthcare settings may support the promotion of preventive health behaviors. Full article

Lung cancer is the most common malignant tumor worldwide in terms of both incidence and mortality, and the development of highly effective, low-toxicity therapeutic strategies remains an urgent clinical challenge. Here, we report that Salvianolic acid A (SAA), a natural compound extracted from Salvia miltiorrhiza Bunge, inhibits the proliferation of non-small cell lung cancer (NSCLC) cells and induces ferroptosis. Mechanistically, SAA acts as an SRC kinase inhibitor, blocking SRC autophosphorylation at Tyr416, thereby disrupting the SRC-YAP interaction and preventing YAP nuclear translocation. This leads to GPX4 downregulation and subsequently triggers ferroptosis, characterized by increased reactive oxygen species (ROS), Fe²⁺ accumulation, and lipid peroxidation. Overexpression of YAP abrogates the effects of SAA, while inhibiting SRC or YAP enhances its activity. SAA inhibits tumor growth and downregulates key effector molecules in vivo. In summary, this study reveals a novel mechanism by which SAA induces ferroptosis via the SRC/YAP/GPX4 axis, supporting its further development as a candidate therapeutic agent for NSCLC. Full article

Purpose: Nucleotide metabolism plays a critical role in cancer development, but the prognostic significance of genetic variants in nucleotide metabolism genes for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients remains unclear. Methods: We performed Cox proportional hazards regression analyses to evaluate the association between genetic variants in 94 nucleotide metabolism-related genes and overall survival (OS) in 866 HBV-HCC patients. To assess the potential biological relevance of the identified variants, the Bayesian false discovery probability and false-positive report probability were applied for multiple testing correction. Results: Two independent SNPs, DCTD rs17074255 G>A (HR = 1.22, 95% CI: 1.06–1.40, p = 0.005) and ENTPD2 rs3763662 G>A (HR = 1.18, 95% CI: 1.03–1.34, p = 0.015), were significantly associated with OS. A significant dose-dependent association between the number of risk genotypes and poorer OS was observed (P_trend < 0.001). Luciferase reporter assays demonstrated allele-specific regulatory effects of rs3763662 on ENTPD2 expression (p < 0.001). DCTD and ENTPD2 mRNA expression levels were significantly elevated in HCC tumors in the UALCAN database and in our 103 paired samples. Higher expression levels of both genes were associated with poorer survival in the TCGA cohort (p = 0.003 and p < 0.001). Conclusions: Our findings suggest that ENTPD2 rs3763662 (supported by direct functional evidence) and DCTD rs17074255 (supported by eQTL and expression associations) may serve as potential prognostic indicators for HBV-HCC through the regulation of mRNA expression. These findings provide new insights into the role of nucleotide metabolism-related genetic variation in HBV-HCC progression and may facilitate prognostic assessment, pending replication in independent cohorts. Full article

Persistent infection with high-risk human papillomavirus (HPV), particularly HPV16, is a major driver of HPV-associated cancers; however, strategies for treating established HPV-induced tumors remain scarce. Here, we developed a DNA-based vaccine linking the SARS-CoV-2 spike (S) protein with an HPV16 E7 epitope (aa 49-57) to simultaneously induce antiviral humoral immunity and antitumor cellular responses. We generated 2 constructs, S-E7 and S-RE7, with the latter incorporating a furin cleavage site (R) to enhance antigen processing. In vitro, S-RE7 significantly enhanced E7-specific CD8⁺ T cell activation compared to S-E7, highlighting the importance of the furin sequence. In vivo, both S-linked vaccines elicited robust E7-specific CD8⁺ T cell responses and provided complete protection against TC-1 tumor challenge in a prophylactic murine model, with long-lasting immunity upon tumor rechallenge. In therapeutic settings, vaccination with S-E7 or S-RE7 significantly suppressed tumor growth, extended survival, and reduced circulating myeloid-derived suppressor cells (MDSCs), indicating alleviation of systemic immunosuppression. Notably, S-RE7 demonstrated faster antitumor effects overall in early tumor progression. In addition to cellular immunity, both constructs induced high levels of anti-spike antibodies, with S-RE7 eliciting approximately fourfold higher responses than S-E7. Furthermore, S-RE7 effectively boosted pre-existing anti-spike immunity in mice that were previously vaccinated. This “two-in-one” strategy represents a promising and versatile platform for the prevention and treatment of HPV-associated cancers while maintaining preparedness against potential SARS-CoV-2. Full article

Background/Objectives: Colorectal cancer (CRC) disproportionately affects Romania, where mortality exceeds the EU average and screening uptake remains low. Diet is among the most modifiable CRC risk factors, yet no validated instrument for assessing nutritional knowledge, attitudes, and practices (KAP) related to CRC prevention exists for the Romanian population. We developed and pilot-tested the EduNutriCRC questionnaire and characterised the corresponding nutritional KAP profile of Romanian adults. Methods: In a cross-sectional pilot study (April–May 2026), a convenience sample of 301 Romanian adults aged 18–74 years completed the 51-item self-administered questionnaire. The instrument was evaluated for internal consistency and dimensional structure (exploratory factor analysis), with non-parametric tests used for group comparisons. Results: The composite knowledge score (C1–C9; maximum 9) was 6.12 ± 2.25 with wide item-level variation. Internal consistency was acceptable, and the Attitudes subscale resolved into two factors (Motivation & Self-Efficacy and Perceived Barriers). Screening engagement was critically low (92.4% never tested; 81.7% unaware of the national programme). Although 64.1% expressed willingness to change their diet, 46.2% reported consuming processed meat at least weekly. Motivation & Self-Efficacy, but not the knowledge score, was inversely correlated with risk-food consumption (ρ = −0.39, p < 0.001). Conclusions: EduNutriCRC demonstrated acceptable psychometric properties at the pilot stage. The study identified prevalent nutritional misconceptions, a marked knowledge–behaviour gap, low screening awareness, and a structural mismatch between information sources used and those trusted. Attitudes and self-efficacy, rather than factual knowledge, were the more proximal correlates of dietary behaviour, supporting the development of self-efficacy-focused, culturally adapted educational interventions for CRC prevention in Romania, with EduNutriCRC serving as a baseline and monitoring instrument. Full article

Human Papillomavirus (HPV) infection is the leading cause of cervical cancer, presenting a significant global health challenge. While natural infection is widespread, the resulting immune response is often characterized by weak, delayed, and type-specific antibody production, offering unreliable protection against reinfection. This review provides a comparative analysis of natural versus vaccine-induced immunity, focusing on antibody kinetics, duration of protection, and cancer prevention efficacy. A comprehensive search of the literature from the last decade was conducted using PubMed, ScienceDirect, and Web of Science. The findings demonstrate that, unlike natural immunity, which is dominated by cellular responses with often incomplete seroconversion, prophylactic vaccination induces high titers of neutralizing IgG antibodies against the L1 capsid protein. These responses are durable, with protection persisting for over a decade, and recent data support the high efficacy of single-dose regimens. Furthermore, vaccination has shown utility in reducing infection persistence in HPV-positive individuals and provides critical protection in immunocompromised groups. Consequently, vaccine-induced immunity is consistently superior to naturally acquired immunity, supporting World Health Organization recommendations for universal vaccination as the primary intervention for reducing the global burden of HPV-related malignancies. Full article

With a lifetime risk estimated to be 1 in 8 in industrialized countries, breast cancer is the most frequent type of cancer among women worldwide and the second leading cause of cancer deaths in women. More importantly, current evidence suggests that in women aged <45 years, breast cancer is unquestionably the leading cause of cancer-related deaths. Hormonal therapy has an established role in the treatment of breast cancer. Hormonal therapy aims at preventing the stimulation of mitogenic estrogen-dependent pathways. Hormonal therapy can be performed through blocking the production of estrogens or through blocking the action of estrogens upon tumor cells. The action of estrogens upon tumor cells can be blocked through selective estrogen receptor modulators (SERMs) or through selective estrogen receptor downregulators (SERDs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or aromatase inhibitors. Fulvestrant, an injectable anti-estrogen, is the SERD commonly used. Fulvestrant has no agonistic activity and causes degradation of the estrogen receptor. This agent is more active in postmenopause than premenopause and is indicated in the treatment of advanced breast cancer in case of disease progression during or after tamoxifen. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Novel agents such as complete estrogen receptor antagonists (CERANs), proteolysis targeting chimeras (PROTACs), and selective estrogen receptor covalent antagonists (SERCAs) are also promising therapies. This manuscript focuses on recent advances in the development of drugs targeting the estrogen receptor. Full article

The United States is experiencing rapid population aging, making geriatric oral health an increasingly important public health and clinical concern. Older adults bear a disproportionate burden of oral diseases, including dental caries, periodontal disease, edentulism, xerostomia, and oral cancer, many of which are closely linked to chronic systemic conditions such as diabetes, cardiovascular disease, and cognitive impairment. This narrative review synthesizes current evidence on oral disease patterns and trends among older adults in the United States, with particular attention to the bidirectional relationships between oral and systemic health. It further examines the organization of oral health care delivery and financing for this population, including the roles of Medicare and Medicaid. Persistent inequities in access to preventive and restorative dental services are highlighted, especially among low-income individuals, racial and ethnic minorities, rural residents, and older adults with functional or cognitive limitations. Workforce shortages, fragmented care models, and limited integration of oral health into primary and geriatric care further exacerbate these disparities. Finally, this review identifies future directions to improve geriatric oral health, including policy reforms to expand dental coverage, integration of oral health into medical and long-term care settings, adoption of minimally invasive approaches, and strengthened interprofessional education and research. Addressing these challenges is essential to promoting healthy aging and reducing oral health disparities among older adults in the United States. Full article