Search Results (1,879)

Head and neck cancer (HNC) patients frequently experience alterations in the oral environment following radiotherapy, including xerostomia and impaired mucosal integrity, which may favour fungal overgrowth. This study aimed to characterise oral Candida colonisation in radiotherapy-treated HNC patients and compare it with that of healthy individuals. Unstimulated saliva samples from 61 HNC patients and 100 controls were cultured on chromogenic agar, and isolates were identified using API 20C AUX or MALDI-TOF. Salivary flow was measured to quantify xerostomia. A representative subset of isolates (10 per group) underwent antifungal susceptibility testing by disk diffusion according to CLSI/EUCAST criteria. Candida colonisation was significantly higher in HNC patients than in controls (64.6% vs. 20%, p < 0.001), with greater species diversity and increased detection of non-albicans yeasts, including C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei. All HNC patients exhibited reduced salivary flow. Azole resistance was more frequent among HNC isolates (26%) than among controls (10%), whereas all isolates remained susceptible to amphotericin B and nystatin. These findings indicate that radiotherapy-associated xerostomia substantially alters the oral mycobiota and underscore the importance of routine species-level identification and antifungal susceptibility testing in HNC patients to guide clinical decision-making. Full article

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma and adenocarcinoma. The H. pylori infection triggers a complex pathogenic cascade within the gastric environment, characterized by prolonged inflammation and heightened oxidative stress, which fosters a milieu of immune dysregulation, where both innate and adaptive immune cells become activated inappropriately, thereby leading to epithelial injury and subsequent remodeling of the gastric tissue. As the infection persists, repeated cycles of inflammation and epithelial damage contribute to the development of epigenetic alterations, including changes in DNA methylation, histone modifications, and non-coding RNA expression, all of which render the gastric epithelium more susceptible to further aberrations, including dysplasia and cancer. In this article, we review the latest advances in understanding the molecular mechanisms of H. pylori-induced gastritis and its role in the progression of gastric cancer, offering new perspectives on the complex biology of this infection and its potential therapeutic implications for preventing the development of gastric malignancies. Full article

Melanoma is the deadliest form of skin cancer, characterized by high metastatic potential and intrinsic heterogeneity. In addition to genetic mutations such as BRAF^V600E^ and NRAS, lipid metabolic reprogramming has emerged as a critical factor in tumor progression and therapy resistance. Lipid metabolism supports melanoma cell survival, phenotypic switching, immune evasion, and resistance to targeted therapies and immunotherapy, while also modulating susceptibility to ferroptosis. This review summarizes current knowledge on lipid dysregulation in melanoma, highlighting alterations in fatty acid synthesis, desaturation, uptake, storage, and oxidation, as well as changes in phospholipids, sphingolipids, cholesterol, and bioactive lipid mediators. These lipid pathways are tightly regulated by oncogenic signaling networks, including MAPK and PI3K–AKT–mTOR pathways, and are influenced by tumor microenvironmental stressors such as hypoxia and nutrient limitation. Advances in lipidomics technologies, particularly mass spectrometry-based approaches, have enabled comprehensive profiling of lipid alterations at bulk, spatial, and single-cell levels, offering new opportunities for biomarker discovery and therapeutic stratification. Targeting lipid metabolic vulnerabilities represents a promising strategy to improve melanoma diagnosis, prognosis, and treatment efficacy. Full article

Background/Objectives: The global rise in multidrug-resistant (MDR) bacteria, particularly methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA and MSSA), continues to pose a major public health challenge, including in Hawaii. This underscores the need to discover new antimicrobial agents from natural sources. Guided by teachings from a Buddhist master regarding the medicinal value of lichens, we investigated the endemic Hawaiian lichen Cladonia skottsbergii. Methods: Specimens of C. skottsbergii were collected from the Lotus Buddhist Monastery in Mountain View, Hawaii. A methanolic extract was prepared and purified using chromatographic techniques, and compound structures were elucidated through spectroscopic analyses and single-crystal X-ray diffraction. The antibacterial activity of the compounds was assessed against Gram-positive strains (MRSA, MSSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa). Cytotoxicity was assessed using A549 (non-small cell lung cancer) and Vero E6 (non-tumorigenic) cell lines. Results: Three compounds were isolated: clarosione (1), a newly identified trichlorinated xanthone, and two known metabolites, (S)-usnic acid (2) and perlatolic acid (3). Compounds 2 and 3 demonstrated strong inhibitory effects against MRSA and MSSA. Their minimum inhibitory concentrations (MICs) ranged from 2 to 4 µg/mL, compared with vancomycin (0.5–1 µg/mL). Cytotoxicity testing showed higher sensitivity in A549 cells than in Vero E6 cells, resulting in favorable selectivity indices for the active compounds. Conclusions: In the current study, a new compound, clarosione (1) was discovered. This enhances our understanding of the constituents of C. skottsbergii and its potential antibacterial properties. Lichen-derived compounds may serve as lead candidates for further development, and further study is warranted. Full article

Dysregulated magnesium (Mg²⁺) homeostasis contributes to colorectal cancer (CRC), yet its context-dependent function within the tumor microenvironment remains unresolved. This study aimed to determine how sustained low and high extracellular Mg²⁺ environments affect CRC spheroid (SP) growth and Mg²⁺ homeostasis using HT-29 SPs. We analyzed Mg²⁺ flux, the expression of Mg²⁺ transporters (e.g., Transient Receptor Potential Melastatin (TRPM) 6), viability, apoptotic and autophagic markers, and phospho-/oxidoproteomic alterations. Both Mg²⁺ extremes destabilized SP architecture, reduced viability, and induced apoptosis and autophagy, with SPs displaying heightened vulnerability relative to 2D cultures. Mg²⁺ stress impaired Mg²⁺ influx and eliminated adaptive transporter regulation in SPs. Loss of membrane TRPM6/7 heterodimers, driven by altered phosphorylation (e.g., TRPM6 Serine 141, Serine 1252, Threonine 1851) and elevated oxidation (e.g., Methionine 1755), suppressed channel activity. High Mg²⁺ caused profound metabolic failure despite increased total Mg²⁺, reflecting functional Mg²⁺ deficiency. CRC spheroids are acutely susceptible to Mg²⁺ imbalance due to collapsed transporter homeostasis and post-translational inhibition of Mg²⁺ channels. These findings reveal a targetable metabolic vulnerability and support the therapeutic potential of localized Mg²⁺ modulation in CRC. Full article

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs. Full article

Familial cancers are caused by inherited mutations in specific genes that regulate cell growth, division, and repair. Approximately 5–10% of all cancer cases have a hereditary component, where germline mutations in certain genes increase an individual’s susceptibility to developing cancer. Two major categories of genes are involved in cancer development: tumour suppressor genes and oncogenes. Both play critical roles in regulating normal cell behaviour, and when mutated, they can contribute to uncontrolled cell proliferation and tumour formation. In addition to genetic mutations, epigenetic alterations also play a significant role in familial cancer. Epigenetics refers to changes in gene expression due to DNA methylation, histone modifications, and the dysregulation of non-coding RNAs without alter the underlying DNA sequence. Familial cancer syndromes follow various inheritance patterns, including autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance, each with distinct characteristics. Identifying genetic mutations associated with familial cancers is a cornerstone of genetic counselling, which helps individuals and families navigate the complex intersection of genetics, cancer risk, and prevention. Early identification of mutations enables personalized strategies for risk reduction, early detection, and, when applicable, targeted treatment options, ultimately improving patient outcomes. Full article

Survival rates for children treated for malignant diseases continue to improve, yet many survivors face persistent late oral complications that affect function, aesthetics, and quality of life. Oncological therapy, especially at a young age and following head and neck radiotherapy or intensive chemotherapy, can disrupt dental and craniofacial development, resulting in dental developmental disorders, enamel defects, salivary gland dysfunction, caries susceptibility, periodontal problems, trismus, and osteoradionecrosis of the jaw. Although these effects are partially known, they are frequently underrecognized in routine practice, and many children do not receive adequate long-term dental follow-up. A key challenge highlighted in the recent literature is the absence of structured, evidence-based guidelines for monitoring and managing late oral effects. The article emphasizes the need for clearer recommendations, better communication of oncological treatment histories, and stronger integration of dental professionals within survivorship care. Developing standardized follow-up protocols will be essential to ensure timely detection, consistent management, and improved oral health outcomes for childhood cancer survivors. This article is intended as a narrative review, synthesizing available evidence from key publications to highlight clinically relevant late oral complications and gaps in current survivorship care. Full article

Pathogenic germline variants in the ATM gene are associated with a 20–30% lifetime risk of breast cancer. Crucially, a relevant fraction of loss-of-function variants in breast cancer susceptibility genes disrupts pre-mRNA splicing. We aimed to perform splicing analysis of ATM splice-site variants identified in the large-scale sequencing project BRIDGES (Breast Cancer After Diagnostic Gene Sequencing). To this end, we bioinformatically selected 47 splice-site variants across 17 exons that were genetically engineered into three minigenes and assayed in MCF-7 cells. Aberrant splicing was observed in 38 variants. Of these, 30 variants, including 7 missense, yielded no or negligible expression of the minigene full-length (mgFL) transcript. A total of 69 different transcripts were characterized, 48 of which harboured a premature termination codon. Some variants, such as c.2922-1G>A, generated complex patterns with up to 10 different transcripts. Alternative 3′ or 5′ splice-site usage was the predominant event. Integration of ATM minigene read-outs into the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based specifications for the ATM gene enabled the classification of 30 ATM variants as pathogenic or likely pathogenic and 9 as likely benign. Overall, splicing assays provide key information for variant interpretation and the clinical management of patients. Full article

Background and Objectives: Lung cancer in never-smokers (LCINS) has become a major global health concern, ranking as the fifth leading cause of cancer-related mortality. Unlike smoking-related lung cancer, LCINS arises from complex interactions between environmental carcinogens and distinct genomic alterations. This review summarizes current evidence on environmental risks, molecular features, and therapeutic progress shaping lung cancer management. Methods: A narrative review was conducted to examine risk factors for lung cancer in non-smokers. Studies reporting driver mutations in never-smokers and smokers were identified across major lung cancer histological subtypes, including small-cell lung cancer (SCLC), lung adenocarcinoma (LUAD), squamous cell carcinoma (SCC), and large-cell carcinoma (LCC). In addition, PubMed was searched for phase III trials and studies on targeted therapies related to driver mutations published between 2016 and 2025. Results: Environmental factors such as cooking oil fumes, radon, asbestos, arsenic, and fine particulate matter (PM_2.5) are strongly associated with LCINS through oxidative stress, DNA damage, and chronic inflammation. EGFR, PIK3CA, OS9, MET, and STK11 mutations are characteristic of never-smokers, in contrast to TP53 mutations, which are more common in smokers. Recent advances in targeted therapy and immunotherapy have improved survival and quality of life, emphasizing the importance of molecular profiling for treatment selection. Conclusions: LCINS represents a distinct clinical and molecular entity shaped by complex interactions between environmental exposures and genetic susceptibility. Genetic alterations promote tumor immune evasion, facilitating cancer development and progression. Continued advances in air quality control, molecular diagnostics, and precision therapies are essential for prevention, early detection, and reduction of the global disease burden. Full article

Urinary bladder neoplasms are clinically relevant in dogs and cats and are also common in humans, all of which may share exposure to environmental factors that influence disease risk. In Veterinary Medicine, however, their etiological determinants remain poorly defined. Urinary bladder neoplasia range from non-invasive lesions limited to the mucosa to invasive forms that infiltrate the muscular layer, which are more aggressive and metastatic. In dogs, invasive urothelial carcinoma (UC) represents the most frequently diagnosed type, while in cats, it is less common but displays similar biological behavior. Hematuria and dysuria are the predominant clinical signs, and although urinary bladder cancer accounts for only a small proportion of canine neoplasms, it is associated with considerable morbidity and mortality. Several risk factors have been identified, including breed, sex, age, obesity, diet, neuter status, and environmental exposures. Female dogs, especially Terrier breeds, are more susceptible, whereas in cats, males and short-haired animals are more often affected. Contact with insecticides, herbicides, and antiparasitic products is a recognized risk factor in dogs, although this association has not been consistently demonstrated in cats. Neutering and obesity appear to increase risk in dogs, and dietary patterns may offer protection, with regular vegetable consumption linked to a reduced incidence. Understanding these determinants is essential to improve early detection, guide preventive measures, and strengthen comparative oncology research. Full article

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation. Full article

Membrane rupture, induced by lipid peroxidation, is a severe threat to osmotic balance, as membrane pores contribute to ferroptosis, an iron-dependent cell death. To alleviate osmotic stress, membrane constituents dynamically reconstruct the membrane and interact with intracellular molecules. Tumor-derived acidosis shift glycolysis-dependent metabolism toward lipid metabolism, increasing polyunsaturated fatty acids (PUFAs). PUFAs enhance membrane fluidity but make cancer susceptible to lipid peroxidation. Also, the ionization of phospholipids under low pH can accelerate membrane rupture. This stress can be mitigated by the redistribution of cholesterol, which maintains tension–compression balance and acts as antioxidants. When excessive reactive aldehydes—byproducts of lipid peroxidation—overwhelm cholesterol’s protective role, lipid peroxides promote membrane cracks. Moreover, a deficiency in glutathione can alter cholesterol’s function, turning it into a pro-oxidant. In contrast, ceramide, derived from membrane lipids, indirectly prevents ferroptosis by facilitating cytochrome c release. This review integrates recent findings on how membrane components and environmental stressors influence ferroptosis. It also suggests potential therapeutic strategies. This could advance our understanding of ferroptosis in cancer. Full article

Background: The belief that “sugar feeds cancer” is widespread and has strongly influenced public perceptions, patient behavior, and dietary recommendations, despite uncertainty regarding its scientific validity. This belief largely stems from misinterpretation of the Warburg effect, which describes altered glucose metabolism in cancer cells rather than dietary sugar dependence. The objective of this review was to critically evaluate whether dietary sugar intake directly contributes to cancer development or progression by examining the totality of epidemiological, experimental, and mechanistic evidence. Methods: We conducted a narrative review of human epidemiological studies, experimental animal and cell-based models, and mechanistic investigations published between 1980 and July 2025. Evidence was synthesized across cancer types, sugar sources, and biological pathways, with careful consideration of study design, exposure relevance, and key confounders, including obesity, insulin resistance, and overall dietary patterns. Results: Across cancer types, epidemiological evidence showed predominantly null or inconsistent associations between sugar intake and cancer risk or outcomes, with positive findings largely confined to metabolically susceptible subgroups and often attenuated after adjustment for adiposity and energy intake. Experimental studies suggested potential tumor-promoting effects under non-physiological conditions, while mechanistic data indicated that sugar influences cancer risk indirectly through insulin signaling, inflammation, and metabolic dysfunction rather than direct tumor fueling. Conclusions: Current evidence does not support the hypothesis that dietary sugar directly “feeds” cancer in humans. Overemphasis on sugar avoidance risks nutritional and psychological harm, particularly among cancer patients. Evidence-based guidance should prioritize overall dietary quality, metabolic health, and patient well-being rather than isolated sugar restriction. Full article

Seasonal biomass-burning haze in Northern Thailand produces sharp fluctuations in ambient fine particulate matter (PM), posing heightened health risks, particularly for individuals with diabetes mellitus (DM). To identify PM-responsive biomarkers and assess whether metabolic status modifies these responses, we first performed small RNA sequencing in a discovery cohort using plasma samples collected during low- and high-PM periods. Thirteen circulating microRNAs (miRNAs) were differentially expressed, including reduced miR-542-3p and elevated miR-29a-3p, novelmiR-203, and novelmiR-754, with predicted targets enriched in immune and endoplasmic-reticulum stress pathways. These four miRNAs were quantified by RT-qPCR in a longitudinal cohort of adults with (n = 28) and without DM (n = 29) sampled at three PM-defined timepoints across one full haze cycle. In non-DM individuals, miR-542-3p decreased at peak exposure while miR-29a-3p and novelmiR-203 increased, with values returning toward baseline at re-exposure. DM participants showed altered baseline levels and attenuated or reversed seasonal changes. Plasma IL-8 rose markedly at peak PM in both groups, mirroring exosome concentration increases measured by NTA, indicating a transient systemic inflammatory response. In an independent clinical cohort, only miR-542-3p differed significantly between lung-cancer patients and healthy controls. These findings indicate that PM exposure reconfigures circulating miRNA, exosomal, and cytokine profiles, and that DM modifies these responses, highlighting miR-542-3p and miR-29a-3p as environmentally responsive and disease-relevant biomarker candidates. Full article