Search Results (608)

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

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

Cadmium is a toxic heavy metal classified by the International Agency for Research on Cancer as a human carcinogen and recognized as an endocrine-disrupting chemical. The present study aimed to evaluate tissue-specific susceptibility to cadmium-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) and to assess the antioxidative effects of melatonin in porcine tissue homogenates representing endocrine (the thyroid and the ovary) and non-endocrine (the liver, the kidney, and the brain) organs. Homogenates were incubated with cadmium chloride (CdCl₂; 2.5–1000 µM) without/with melatonin (0.1–5.0 mM). Lipid peroxidation was assessed spectrophotometrically by measuring malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) levels. Cadmium significantly increased LPO in the liver (2.5–1000 μM) and in the kidney (25–1000 μM), whereas no prooxidative effect was observed in endocrine tissues or in the brain. Liver damage was mitigated by melatonin doses as low as 0.1 μM across the 250–1000 μM cadmium range, while protection in the kidney was limited to higher melatonin concentrations (2.5–5.0 mM) against damage induced by 100–1000 μM cadmium concentrations. The findings demonstrate pronounced tissue-specific differences in susceptibility to cadmium-induced oxidative stress and support the potential of melatonin as a preventive agent against heavy metal-induced oxidative stress, particularly in non-endocrine organs. Full article

Codonopsis lanceolata has long been used in traditional medicine across East Asia; however, recent scientific investigations have increasingly highlighted its broad therapeutic potential. This review provides an updated and comprehensive overview of the pharmacological properties of C. lanceolata and its bioactive constituents, focusing on their roles in disease prevention and therapy. Evidence from in vitro, in vivo, and limited clinical studies suggests that C. lanceolata possesses antidiabetic, anti-obesity, and anti-cancer properties while showing protective effects in experimental models of cardiovascular dysfunction, liver injury, neurodegenerative disorders, skeletal muscle atrophy, and pulmonary damage. Additionally, its immunomodulatory effects contribute to improved host defense and regulation of inflammatory responses. These diverse actions are mediated by mechanisms involving antioxidant activity, inhibition of inflammatory signaling, regulation of metabolic pathways, modulation of apoptosis, and maintenance of tissue integrity. Despite promising findings, challenges remain regarding extract standardization, identification of key active compounds, and the translation of preclinical results into clinical efficacy. Future research integrating molecular, pharmacokinetic, and clinical approaches is essential to clarify the therapeutic value and establish its potential as a nutraceutical or therapeutic agent. This review highlights the promising pharmacological potential and identifies key directions for future research to support its potential application in modern medicine. Full article

Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies. Full article

Background: Biliary tract cancers (BTCs), encompassing cholangiocarcinoma and gallbladder carcinoma, are aggressive malignancies with poor prognosis and increasing incidence in selected regions worldwide. Advances in imaging, biomarker profiling, immunotherapy, and targeted therapies have improved treatment options but have also increased the economic pressure on health systems. Understanding the economic evidence on BTC is therefore important for resource allocation and health technology assessment. Methods: We systematically searched PubMed/MEDLINE, Embase, Scopus, and Web of Science for peer-reviewed economic studies of BTC published from January 2010 to March 2025. Eligible studies included cost-effectiveness, cost–utility, cost–benefit, cost-of-illness, and resource-use analyses. The review followed PRISMA reporting principles. Reporting completeness was assessed using CHEERS 2022, and methodological credibility was appraised using the Drummond framework. Results: Twenty studies were included: 13 cost-effectiveness or cost–utility analyses and seven cost-of-illness or resource-use studies. Conventional chemotherapy strategies, including gemcitabine plus cisplatin in some settings and other cytotoxic combinations in selected jurisdictions, generally produced more favorable economic results than newer systemic therapies, although findings varied by country, threshold, comparator, and price assumptions. First-line immunotherapy combinations and biomarker-directed targeted therapies frequently produced ICERs above jurisdiction-specific willingness-to-pay thresholds at current prices, often requiring substantial price reductions to approach cost-effectiveness. Real-world studies showed high resource use and costs, particularly with hospitalizations and later treatment lines. Evidence on screening and prevention was limited, with one study suggesting that ultrasound surveillance may be cost-effective in a liver fluke-endemic region of Thailand. Discussion: The available economic evidence suggests that affordability and jurisdiction-specific value assessment are central to BTC policy decisions. Current prices for several immunotherapy and targeted agents limit cost-effectiveness in published models, while evidence on prevention, early detection, and care-pathway interventions remains sparse and context-specific. Full article

Insulin resistance (IR) is traditionally viewed within the context of type 2 diabetes. However, it increasingly appears to represent a broader systemic metabolic risk state with potential relevance for carcinogenesis. Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis. At the same time, IR is closely linked to oxidative stress, chronic low-grade inflammation, and epigenetic alterations, together shaping a tumor-promoting microenvironment. Epidemiological studies report consistent associations between IR and increased cancer risk, particularly for endometrial, liver, and colorectal cancers. Yet causality remains uncertain and likely varies by tumor type. Notably, metabolic dysfunction may also occur in individuals with normal body mass index (BMI), underscoring the limitations of BMI-based risk assessment. Unlike previous reviews that primarily focused on individual mechanisms or epidemiological associations, this review examines IR as a systemic metabolic risk state by integrating molecular, epidemiological, biomarker-based, and prevention-oriented perspectives. Particular emphasis is placed on strategies for earlier risk identification using integrated biomarker approaches, including fasting glucose, homeostatic model assessment of insulin resistance, triglyceride-to-high-density lipoprotein ratio, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Emerging tools such as continuous glucose monitoring and hepatokine profiling may further refine risk detection. Sustained lifestyle modification—diet, physical activity, sleep, and stress regulation—remains central to prevention. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification. Full article

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the leading causes of cancer-related mortality globally, with its incidence increasingly driven not only by viral hepatitis and alcohol-related etiologies but also by metabolic dysfunction-associated steatotic liver disease. Dietary intake can modify gut microbial activity and the production of microbial metabolites, which in turn may regulate hepatic immune signaling and metabolic pathways along the gut–liver axis. Microbiota-derived metabolites have emerged as important immunometabolic mediators linking dietary factors to hepatic immune responses and metabolic reprogramming. These metabolites, which have been shown to influence hepatic immune cell function and inflammatory signaling, include short-chain fatty acids, secondary bile acids, and tryptophan-derived indoles. Changes in the production and composition of these metabolites have been associated with immune dysregulation, chronic inflammation, and metabolic reprogramming that promote hepatocellular carcinoma development. This review highlights how diet–microbiota interactions reshape hepatic immunometabolism and discusses their potential translational relevance for prevention and therapeutic strategies in hepatocellular carcinoma. Full article

Breast cancer remains the most frequently diagnosed malignancy among women worldwide, while metabolic dysfunction-associated steatotic liver disease (MASLD) represents the leading cause of chronic liver disease, reflecting a global burden of metabolic dysfunction. Increasing evidence suggests that MASLD is associated with breast cancer development and progression; however, whether this relationship reflects an independent effect of hepatic metabolic dysfunction or the broader metabolic environment remains uncertain. This review synthesizes current epidemiological, clinical, and mechanistic data linking hepatic metabolic dysfunction to breast carcinogenesis. Population-based studies consistently demonstrate an association between hepatic steatosis and increased breast cancer incidence, particularly in postmenopausal and metabolically vulnerable populations, as well as poorer oncological outcomes. Mechanistically, MASLD promotes a systemic pro-tumorigenic environment through interconnected pathways, including insulin resistance, hormonal dysregulation with increased estrogen bioavailability, chronic inflammation, oxidative stress, lipid metabolic reprogramming, and gut–liver axis disruption. Hepatokines, particularly fibroblast growth factor 21 (FGF21), emerge as key mediators of tumor progression and potential biomarkers of metabolic vulnerability, while Fetuin-A and angiopoietin-like protein 8 (ANGPTL8) further support the liver’s endocrine role in oncogenic signaling. Preclinical evidence highlights fatty acid oxidation as a metabolic dependency in aggressive breast cancer subtypes, suggesting novel therapeutic targets. Despite consistent associations, causality remains unproven. Future prospective studies are needed to determine whether targeting metabolic dysfunction can improve breast cancer prevention and outcomes. Full article

The clinical management of nutrition in acute and chronic diseases requires an integrated understanding of the interactions between energy intake, dietary protein, and amino acids (AAs). Many conditions (including sepsis, major trauma, cancer cachexia, chronic heart failure, chronic obstructive pulmonary disease, renal and liver failure, autoimmune diseases, and aging) share a common pathophysiological feature: the hypercatabolic state (HCS). HCS is characterized by systemic inflammation and neuroendocrine activation that increase basal metabolic rate, induce insulin resistance, and accelerate skeletal muscle proteolysis, leading to negative nitrogen balance, sarcopenia, and cachexia. Under these conditions, skeletal muscle acts as a metabolic reservoir of AAs mobilized to support energy production, gluconeogenesis, immune function, and vital organ metabolism, often at the expense of lean body mass and clinical outcomes. This narrative review examines the distinct and non-overlapping roles of calories, proteins, and AAs in metabolic regulation, with a particular focus on HCS. Calories primarily act as a permissive factor for protein utilization, whereas proteins and especially essential amino acids (EAAs) function not only as substrates for protein synthesis but also as signaling molecules (metabokines) regulating anabolic and catabolic pathways, including mTORC1 and AMPK. Energy provision alone is insufficient to prevent muscle loss when EAA availability is inadequate, while high protein intake without sufficient energy fails to sustain anabolism due to anabolic resistance. Evidence indicates that protein quality and the balanced availability of all EAAs are more critical for lean mass preservation than total caloric intake alone. Strategies based solely on calorie provision or protein quantity are therefore limited, whereas targeted EAA supplementation may partially overcome anabolic resistance in selected hypercatabolic conditions. Overall, this review supports a shift from calorie-centered nutrition toward a signal-based, quality-oriented approach, based on personalized needs, that integrates metabolic status, protein quality, and AA signaling to preserve lean body mass and improve clinical outcomes. Full article

Aristolochic acid (AA), a naturally occurring compound found in Aristolochia plants, is a well-established nephrotoxin and Group 1 carcinogen. Emerging evidence suggests a potential link between AA exposure and hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide. This review critically evaluates current knowledge on AA’s hepatic metabolism, its formation of persistent DNA adducts, and the induction of inflammatory responses in the liver. Based on preclinical and indirect human evidence, we propose a working hypothesis that AA may contribute to hepatocarcinogenesis through a dual mechanism: genotoxic (primarily via H-ras and p53 mutations resulting from AA-DNA adducts) and non-genotoxic (via chronic inflammation involving IL-6, TNF-α, and NF-κB activation, as well as epithelial–mesenchymal transition). We note, however, that these mechanisms remain to be validated in human cohorts and do not yet establish causality. Recent studies have identified novel mechanisms, including PDK4-mediated mitochondrial dysfunction, ferroptosis inhibition via p53 hijacking, and ARID1A deficiency as a susceptibility factor. A recent meta-analysis quantified a significantly increased risk of liver cancer following AA exposure in epidemiological studies. While direct causal evidence in humans remains limited, the high mutational burden observed in AA-exposed liver tissues warrants caution. Nevertheless, the primary public health priority pertains to the prevention of AA exposure. Further epidemiological and mechanistic studies are urgently needed. Full article

Hepatocellular carcinoma (HCC) incidence in Texas is 45% higher than the national average, with disproportionate burden among the Hispanic/Latino population. Despite significant health disparities, comprehensive evidence on HCC risk factors specific to this population remains limited. This scoping review of 20 primarily observational studies utilized PubMed, EbscoHost, and the PRISMA-ScR checklist to map risk factors in south Texas. Results show that metabolic dysfunction, specifically diabetes and obesity, increases advanced liver disease odds by 7- to 12-fold compared to non-Hispanic groups. Environmental exposures are also significant: aflatoxin was detected in 5.7 to 7.3% of Hispanic/Latino HCC tumors, and cases demonstrated 6-fold higher odds of aflatoxin biomarkers, while alcohol contributed to 3.0% of cancers. Furthermore, PNPLA3 genetic variants exerted synergistic effects with obesity and heavy alcohol consumption. Among four intervention studies, strategies included low-dose calcium montmorillonite clay for aflatoxin reduction, community-health-worker-integrated chronic care, and hospital-based hepatitis screening. However, critical research gaps remain regarding multirisk factor interactions, toxin dose–response characterization, dietary interventions, and longitudinal data. These findings underscore the urgent need for culturally tailored, community-engaged prevention programs and ethnicity-specific HCC guidelines for the Texas Hispanic/Latino population to effectively address these rising health disparities. Full article

Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K/Akt, MAPK, NF-κB, and Nrf2. The interplay between these pathways underpins DHM’s efficacy across disease models. Furthermore, we highlight structure–activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. The updated terminology reflects a conceptual shift by emphasizing metabolic dysfunction rather than excluding alcohol consumption. This redefinition introduced MetALD, a subtype characterized by the coexistence of cardiometabolic risk factors and moderate alcohol intake. In the world, misclassification of MetALD as MASLD is frequent, often due to underreporting of alcohol consumption, which may distort epidemiological estimates. In Mexico, where both obesity and alcohol use are highly prevalent, this reclassification carries important implications for diagnosis, prognosis, and public health policy. This review summarizes the current evidence on MASLD and MetALD, highlighting their prevalence, diagnostic challenges, and implications for liver transplantation and cancer surveillance. We advocate for integrating these diseases into national non-communicable disease policies and adopting a multidisciplinary, preventive approach tailored to the Mexican context. Full article

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and accounts for over 800,000 deaths worldwide, making it a major global health concern. Unfortunately, despite major advances in systemic treatments, such as the introduction of atezolizumab and bevacizumab, patient objective response rates fall below 30%. HCC most commonly develops against a background of chronic liver disease and cirrhosis, although single gene mutations can also drive HCC development, progression, and metastasis. Around 25% of HCC patient tumours carry mutations in TP53, the gene encoding the tumour-suppressor protein p53. p53 is a central regulator of genomic stability, cell-cycle arrest, apoptosis, senescence, and metabolic homeostasis, and its dysfunction is a frequent event in hepatocarcinogenesis. Accumulating evidence highlights the critical role of p53 in liver fibrosis, inflammation, and shaping of the HCC tumour microenvironment (TME). This review summarizes the role of p53 and its negative regulators Mdm2 and MdmX in HCC development and progression, with an emphasis on how p53 shapes the TME in favour of tumour progression. We also evaluate current and emerging p53-targeted therapeutic strategies, including Mdm2/MdmX inhibitors, mutant p53 reactivators, and rational combinations with immunotherapies. Finally, we discuss major challenges in translating p53-based therapies to the clinic, such as tumour heterogeneity, underlying liver dysfunction, and the development of therapeutic resistance. A deeper understanding of p53 biology in chronic liver disease may unlock new avenues for effective HCC prevention and treatment. Full article