Testicular germ cell tumors (TGCTs) are the most common malignancies in young-adult males and represent a biologically heterogeneous group of neoplasms. Despite excellent overall prognosis, conventional serum tumor markers lack sufficient sensitivity and specificity in several key clinical settings, including early metastatic disease, postchemotherapy residual masses, and surveillance. Over the past decade, microRNAs of the miR-371~373 cluster have emerged as highly accurate biomarkers in this setting. Among them, circulating miR-371a-3p has demonstrated sensitivity and specificity exceeding 90% for viable, nonteratomatous TGCTs across multiple cohorts, consistently outperforming traditional markers. miR-371a-3p levels closely reflect tumor burden, showing rapid decline after orchiectomy and during effective chemotherapy, and rising at relapse, enabling near real-time disease monitoring. Importantly, miR-371~373 is differentiation-dependent (which can be used as readout for studies on the pathobiology of TGCT phenotypes). It is present in nonteratomatous germ cell components, uniformly absent in teratoma and absent/low in somatic-type malignancies, a feature that both underpins its clinical utility and defines one of its main limitations. This review summarizes the biological rationale underlying miR-371~373 expression in TGCTs and examines current clinical applications of miR-371a-3p across diagnosis, staging, surveillance, and postchemotherapy assessment. Moreover, we discuss analytical considerations, health-economic implications, and emerging data in the biologically related ovarian and extragonadal germ cell tumors. Remaining challenges and future directions for standardized clinical implementation are also addressed.

Background and objectives Lipidomics has advanced cancer research by uncovering biomarkers that reveal key mechanisms of tumourigenesis. By analysing endpoint lipid metabolites influenced by genetic and environmental factors, the lipidome closely reflects a cell's functional state. Mass spectrometry, strengthened by modern bioinformatics and biostatistics, now enables precise detection of cancer-related lipid changes, motivating us to adopt this approach. Methods We have applied advanced mass spectrometry and machine-learning methods to develop a novel tool for cervical cancer screening, the second most common cancer in India. The study included cervical cancer patients diagnosed through cytology, HPV testing, histopathology, or imaging, along with healthy volunteers as controls. Serum samples from all participants were analysed using Ultra High Performance Liquid Chromatography coupled with high-resolution Orbitrap Mass Spectrometry using a targeted approach for lipid biomarker discovery. Results A comprehensive evaluation of controls and cervical cancer patients across clinical stages revealed distinct lipidomic patterns and biomarker differences. We identified a 3-biomarker panel [LPE (22:6)+H, PE (18:1_20:4)+H, and MG (20:0)+H] effective for early-stage detection and a 4-biomarker panel (LPE (22:6)+H, PE (18:1_20:4)+H, PC (16:1_20:5)+H, and TG (16:0_18:1_18:3)+H) suitable for comprehensive cervical cancer screening. The combined ROC for the 3-biomarker panel showed 88% sensitivity, 93% specificity, 90% accuracy, and an area under the curve (AUC) of 0.945, while the 4-biomarker panel achieved 87% sensitivity, 84% specificity, 86% accuracy, and an AUC of 0.946. Interpretation and conclusions Our study demonstrates a clear link between altered lipid metabolism and cervical cancer, paving the way for future research to identify new diagnostic and prognostic markers and ultimately enabling earlier detection and timely intervention.

Chemoresistance remains a major clinical challenge in osteosarcoma, primarily driven by inefficient drug delivery and the evasion of cell death. Here, a multifunctional poly(β-amino ester) (pBAE)-based therapeutic delivery system was developed for simultaneous codelivery of small interfering RNA (siRNA) and doxorubicin (DOX) to drug-resistant osteosarcoma cells. The system significantly enhanced siRNA transfection within 4 h and showed substantially enhanced cytotoxicity compared with free DOX at equivalent concentrations. Mechanistically, pBAE degraded in the acidic tumor microenvironment, facilitating siRNA and DOX release, which synergistically modulated apoptotic and pyroptotic signaling to induce cell death. In vivo studies in osteosarcoma-bearing mice demonstrated that pBAE-based treatment markedly suppressed tumor growth, reducing tumor volume by approximately 70% without significant adverse effects. This study presents a therapeutic strategy centered on the "enhanced delivery-induced cell death" paradigm, effectively overcoming osteosarcoma chemoresistance and designing multifunctional nanodelivery systems for cancer therapy.

Capecitabine (Cap) is widely used in the treatment of advanced gastric cancer; however, the emergence of acquired resistance remains a major obstacle to its long-term efficacy. Although several gastric cancer models resistant to 5-fluorouracil (5-FU) have been reported, experimentally characterized gastric cancer models of Cap resistance remain limited.

This study aimed to establish and characterize a Cap-resistant MKN-45 gastric cancer cell model. with a focus on phenotypic alterations associated with acquired drug adaptation.

A Cap-resistant MKN-45 subline (MKN-45/R-CapIC₆₀) was generated through exposure of parental MKN-45 cells to gradually increasing concentrations of Cap. Cell viability was evaluated using the MTT assay. Morphological alterations were examined by phase-contrast microscopy, while apoptosis, cell-cycle distribution, and surface c-Met expression were analyzed by flow cytometry.

The established resistant subline exhibited a moderate level of Cap resistance, with an approximately 2- to 4-fold increase in the resistance index (RI) compared with the parental cells. Resistant cells showed morphological remodeling characterized by an elongated spindle-like morphology and increased adherence to the culture surface compared with parental cells. Surface c-Met expression was altered in resistant cells and further decreased following Cap exposure. Despite the acquisition of a resistance phenotype, Cap exposure retained biological activity in resistant cells by reducing proliferation, altering cell-cycle distribution through impaired G1/S transition, and increasing late apoptotic/necrotic populations.

The findings suggest that the established Cap-resistant gastric cancer cell model retains responsiveness to Cap exposure despite the acquisition of a resistance phenotype. This model may provide a useful platform for investigating early phenotypic adaptations associated with the development of drug resistance in gastric cancer.

Oral epithelial dysplasia (OED) is the principal histopathological marker for malignant risk stratification in oral potentially malignant disorders (OPMDs). Current World Health Organisation (WHO) three-tier and other binary grading systems are limited by modest inter-observer reproducibility and suboptimal prognostic discrimination, particularly for architecture-predominant lesions where cytological atypia is inconspicuous. The most clinically consequential failure of current practice is not mis-grading but non-recognition of dysplasia altogether, with direct implications for patient surveillance and management.

This position paper, arising from Working Group 2 of COST Action CA21140 INTERCEPTOR, synthesises evidence from inter-observer reproducibility studies, feature-based prognostic models, under-recognition studies, outcome data and computational pathology analyses to propose and contextualise a pattern-anchored, grade-retaining diagnostic framework for OED.

Five recognisable histological patterns are proposed: conventional/basaloid, keratinising/differentiated, verrucous, papillomatous, and HPV-associated, functioning as diagnostic anchors that capture the full morphological spectrum of OED, including architecture-predominant phenotypes that are disproportionately under-recognised in routine practice. Feature-based prognostic models demonstrate that architectural traits characterising these patterns (bulbous rete ridges, AUROC 0.74; cohesion loss, AUROC 0.73) predict malignant transformation more effectively than grade alone. Independent computational pathology analyses identify corresponding immune microenvironment and architectural signals as the strongest prognostic variables, providing convergent support.

A two-step approach i.e. first identifying the dominant morphological pattern and then assigning grade within that pattern using existing WHO or binary criteria, offers a pragmatic, grade-retaining refinement compatible with current diagnostic frameworks and clinical pathways. The proposal is hypothesis-driven and requires prospective multicentre validation before wider adoption.

Osteosarcoma remains one of the most aggressive primary malignant bone tumor, despite all the treatment options available, there has been little progress in osteosarcoma treatment in children and young adults with metastatic or recurrent osteosarcoma. The link between dysregulated microRNAs (miRNAs) in osteosarcoma pathogenesis, metastasis, chemoresistance and immune system regulation increasingly shows that they are important drug targets for novel therapies. The clinical application of naked miRNAs is dramatically limited by the fact that they are rapidly degraded by nucleases, have a poor uptake by the cells, are poorly specific for tumors and may lead to off-target effects. Solution to these challenges is one of the innovative delivery systems based on nanocarriers that provides increased stability of miRNA, improvement of pharmacokinetics, improvement of cellular entry and a controlled release. The present review critically analyzes the ongoing developments of miRNA therapeutics for osteosarcoma focusing on the various nanocarriers such as polymeric, lipid-based, inorganic, hybrid and exosome-based nanocarriers. Rather than providing a description of every type, the review compares them based on loading capacity, biodistribution, tumor infiltration capabilities, biodegradability, their safety profiles, and potential for real-world applications. It highlights some of the main challenges of targeted drug delivery in the mineralized bone microenvironment and presents some new ideas in order to enhance the targeting of skeletal tumors with ligand-mediated and stimuli-responsive nanocarriers. The review also highlights the state-of-the-art progress in the clinical development of miRNA therapeutics, the lessons learned from those in clinical trial phases, and the major challenges to clinical application of miRNA therapeutics such as toxicity in the immune system, manufacturing scalability, batch-to-batch variability, formulation instability, regulatory issues, and cost considerations. Finally, emerging research areas are discussed, with a focus on those trends that involve advances in personalized nanomedicine (evidence-based) and strategic nanocarrier design. While there are hopeful signs of miRNA nano therapy's potential in the treatment of osteosarcoma, significant biological, technological, and regulatory hurdles remain that need to be overcome for this innovative therapy to be translated to the clinic.

Apoptosis has traditionally been viewed as an irreversible, tumor-suppressive process, with mitochondrial outer membrane permeabilization (MOMP) representing the decisive "point of no return" that irrevocably commits cells to death. Classical models described MOMP as a rapid, synchronous, all-or-none event leading to caspase activation and cellular demise. However, accumulating evidence now challenges this binary view, revealing that both MOMP and downstream caspase activity are threshold-dependent processes that can produce diverse non-lethal outcomes. Under specific conditions, cells can survive or recover from MOMP and downstream apoptotic signaling, fundamentally reshaping our understanding of cell fate decisions. Failed apoptosis and anastasis lie at the center of this paradigm shift, revealing unexpected plasticity in apoptotic outcomes. Failed apoptosis occurs when limited MOMP triggers sublethal yet sustained caspase activity, leading to DNA damage, chromosomal instability, and prolonged cellular reprogramming, thereby accelerating oncogenesis and tumor progression. In contrast, anastasis describes a remarkable recovery process in which cells rebound from late-stage apoptosis after the removal of apoptotic stimuli. Recovered cells exhibit acquired enhanced stress tolerance and oncogenic traits, raising concern about their role in therapy failure, cancer progression, and relapse. This review discusses the molecular mechanisms governing MOMP initiation and subsequent apoptotic signaling, with particular emphasis on new insights into the reversibility of apoptosis. It highlights the concepts of failed apoptosis and anastasis as adaptive responses that influence cell fate, integrating current research, experimental tools and challenges, and their physiological relevance and clinical implications. By describing these survival pathways, the review aims to enhance our understanding of the reversibility of apoptosis and emphasize its relevance to cancer progression, metastasis, and resistance to therapy. These insights may help develop more effective cancer treatments and improve patient outcomes.

Recent research has focused on gut bacteria in colorectal cancer, but the influence of other microbiota, including oral and nonbacterial gut microbiota, on treatment efficacy remains insufficiently explored. This study aimed to investigate their relationship with the efficacy of neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Saliva and fecal samples were collected from patients with LARC before treatment. Shotgun metagenomic sequencing was used to profile bacterial, archaeal, eukaryotic, and viral taxonomic groups and to examine oral and gut microbial functions. An artificial intelligence-based prediction model was developed by integrating oral and gut microbiome data with clinical information. Statistical analyses compared diversity and response-associated microbial features between responders and non-responders to nCRT. Response-associated differences were observed in bacterial and nonbacterial taxonomic profiles and in oral and gut microbial functional profiles. In the internal test subset, the integrated analysis yielded an observed AUC of 0.917. Given the small cohort and the exploratory comparison of candidate classifiers, this estimate requires confirmation in larger, independent cohorts. Baseline oral and gut microbiome profiles were associated with response to nCRT. Integrating microbiome and clinical features showed potential for response prediction, but the model remains exploratory and requires validation in larger, independent cohorts before clinical application. Retrospectively registered on 01/08/2026, NCT07346729.

To describe the experiences of Turkish fathers whose child is undergoing cancer treatment.

Participants were recruited at the pediatric hematology-oncology clinic of a university hospital in western Türkiye. A purposive sampling strategy was used to identify eligible fathers. Fathers whose child was aged 0-18 years and receiving cancer treatment were considered eligible.

This study was conducted using a descriptive qualitative research design. Semistructured individual interviews with 12 fathers of a child with cancer were used for data collection. Data were analyzed using the content analysis method.

The fathers' (N = 12) mean age was 36.83 years, and the children's mean age was 5.25 years. The following four main themes with interrelated subthemes and categories were identified that reveal the feelings, experiences, and expectations of fathers of children with cancer: diagnosis and treatment process experiences, postdiagnosis life changes, coping, and needs.

Pediatric oncology nurses can develop more inclusive care practices that support paternal involvement by considering the influence of gender roles on fathers' emotional expressions and help-seeking behaviors. Future research should examine fathers' experiences across diverse cultural and clinical settings to inform the development of father-focused interventions.

To evaluate the effect of yoga breathing exercise (YBE) on perceived stress and sleep quality in women with breast cancer undergoing chemotherapy.

This randomized, sham-controlled trial was conducted in the chemotherapy unit of a university hospital in Türkiye from November 2023 to April 2024 and involved 60 women with stage II-III breast cancer undergoing chemotherapy.

Participants were randomized to a YBE group or a sham breathing group. Both groups received standard oncology care, and the YBE group additionally practiced 4-4-4-4 yoga breathing twice daily for five minutes during 21 days. Data were collected at baseline and after the 21-day intervention period. Perceived stress and sleep quality were assessed using the Perceived Stress Scale and the Pittsburgh Sleep Quality Index. Data were analyzed using two-way repeated-measures analysis of variance.

After 21 days, the YBE group showed significantly greater reductions in perceived stress (mean difference = -6.23, p < 0.001) and improved sleep quality (mean difference = -2.1, p < 0.001) compared with the sham group. No adverse events were reported.

YBE can be integrated into supportive oncology nursing care as a low-cost, nonpharmacologic intervention to address stress and sleep disturbances during chemotherapy.