Prostate cancer (PCa) remains one of the most prevalent malignancies and a major cause of cancer-related deaths among men worldwide. Current pre-biopsy evaluation relies primarily on serum prostate-specific antigen (PSA) testing and multiparametric MRI (mpMRI), but both approaches have limited specificity, particularly in the diagnostic gray zone (PSA 4-10 ng/mL and/or equivocal MRI findings such as Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions). In this setting, overlap between PCa and benign prostatic diseases frequently leads to unnecessary biopsies. This unmet clinical need has driven the development of novel diagnostic strategies designed to better discriminate PCa from benign prostatic diseases before biopsy. In this review, we provide a comprehensive overview of recent advances in non-invasive diagnostic strategies, including liquid-based molecular biomarkers, advanced imaging modalities, and multimodal integrative frameworks. These advances may improve diagnostic accuracy, reduce unnecessary biopsies, and support personalized risk stratification and biopsy decision-making. Moreover, we highlight the paradigm shift from single-parameter screening to multimodal integration, including artificial intelligence-based approaches in early PCa screening. Overall, these non-invasive strategies may help reduce diagnostic uncertainty in the gray zone and support more precise and personalized biopsy decision-making.

The current classification of pulmonary neuroendocrine neoplasms (NENs) is primarily based on histomorphological criteria, which do not fully capture their underlying biological heterogeneity. This limitation is particularly evident among pulmonary carcinoids, a subgroup characterized by highly variable clinical behaviour and prognostic outcomes despite similar morphological features.Angiogenesis is a hallmark of NENs, yet the role of the vascular endothelial growth factor (VEGF) pathway in pulmonary NENs remains incompletely defined.In this multicentre retrospective study, 109 pulmonary NENs (67 typical carcinoids, 22 atypical carcinoids, and 20 high-grade NENs) were analysed. VEGF, VEGFR1, VEGFR2, and VEGFR3 expression was assessed by immunohistochemistry and correlated with clinicopathological features and outcome.VEGF pathway components showed subtype-specific expression patterns. VEGFR1 was reduced in high-grade tumours and displayed a bimodal distribution, while VEGFR2 and VEGFR3 were higher in atypical carcinoids and high-grade tumours. Survival and recurrence were driven by histological subtype, whereas VEGF pathway expression lacked independent prognostic significance.The higher expression of VEGFR2 and VEGFR3 observed in atypical carcinoids and high-grade neuroendocrine carcinomas suggests a possible involvement of the VEGF signalling pathway in tumour biology. These findings contribute to the biological characterization of pulmonary NENs and provide a rationale for future studies investigating whether VEGF pathway markers may have predictive relevance for anti-angiogenic therapies.

Tumor-associated neutrophils (TANs) display functional plasticity in lung adenocarcinoma (LUAD), but subsets linked to immune exclusion are poorly defined.

We integrated single-cell RNA-seq, spatial transcriptomics, and bulk multi-omics data to characterize neutrophil heterogeneity in LUAD. Key findings were validated by immunofluorescence co-localization and qPCR on clinical blood and isolated neutrophils.

Neutrophils exhibited the highest scores for an EMT-associated transcriptional program and immune exclusion among all immune cell types. A distinct JUNB+ neutrophil subpopulation was spatially enriched in immune-excluded tumor regions and correlated with unfavorable prognosis. Spatial transcriptomic analysis revealed a significant positive correlation between JUNB expression and neutrophil marker module scores across tissue spots (Pearson r = 0.216 and 0.205, P = 1.84 × 10^-10 and 9.06 × 10^-11). Immunofluorescence confirmed JUNB protein co-localization with CD66b+ neutrophils in LUAD tissues (54.3% ± 8.2% of CD66b+ cells JUNB +). qPCR revealed specific upregulation of JUNB mRNA in circulating neutrophils from LUAD patients, whereas no difference was observed in whole blood.

This study identifies JUNB as a marker of a neutrophil state associated with immune exclusion and poor prognosis in LUAD. The neutrophil-specific upregulation of JUNB highlights its potential as a circulating biomarker for TAN-mediated immunosuppression, which warrants validation in prospective cohorts.

UBTF tandem duplications (UBTF-TD) define a recently recognized high-risk subtype of pediatric myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). UBTF-TD myeloid neoplasms are driven by a HOX/MEIS1 transcriptional program that depends on the interaction between menin and KMT2A. Preclinical studies have shown sensitivity to menin inhibition, but clinical experience in children with MDS remains scarce.

We report a ten-year-old girl with MDS with excess blasts harboring UBTF-TD together with NRAS and WT1 mutations. During the first cycle of azacitidine and venetoclax, blood counts did not improve, and the patient remained dependent on platelet and red blood cell transfusions. Revumenib was added to the ongoing treatment. Within two weeks, platelet counts and hemoglobin increased markedly, the patient became transfusion independent, and bone marrow blasts cleared. UBTF-TD also became undetectable by molecular testing. The patient subsequently underwent allogeneic hematopoietic stem cell transplantation and remains in complete remission with full donor chimerism one year after transplantation.

The rapid hematologic recovery and clearance of both bone marrow blasts and detectable UBTF-TD after initiation of revumenib provide clinical evidence that the menin dependency of UBTF-TD myeloid neoplasms can be therapeutically exploited. The timing and depth of the clinical and molecular response were remarkable.

Ataxia-Telangiectasia (A-T) is a rare, autosomal recessive disorder caused by biallelic pathogenic variants in the ATM gene. Loss of ataxia-telangiectasia mutated (ATM) protein function impairs DNA damage responses, leading to progressive neurodegeneration, genomic instability, immunodeficiency, and an increased risk of malignancy. Some A-T patients develop cancers at a young age and display extreme sensitivity to ionizing radiation and certain chemotherapeutics. Therefore, standard treatments often cause severe, life-threatening toxicities in these patients. This review discusses the dual role of ATM as a tumor suppressor and key DNA repair kinase, the mechanisms by which ATM deficiency promotes oncogenesis, and the unique challenges of treating malignancies in the context of A-T. We highlight emerging, less genotoxic therapies for ATM-deficient cancers including cancer vaccines, immune checkpoint inhibitors, CAR T-cell therapy, and synthetic lethal approaches such as Poly(ADP-ribose) polymerase (PARP) and Ataxia Telangiectasia and Rad3-related (ATR) inhibitors. These novel strategies may improve outcomes for A-T patients while minimizing treatment toxicity. We also outline future directions and clinical implications, emphasizing the need for tailored therapeutic approaches and multidisciplinary care for this high-risk population. Because prospective, A-T-specific therapeutic data are scarce, we draw extensively on the broader literature on somatic ATM-mutant cancers to inform management, while highlighting the additional constraints imposed by germline ATM loss.

Primary aortic wall myxoma is exceptionally rare and may mimic mural thrombus or acute aortic dissection.

A 38-year-old man presented after approximately 12 hours of acute left lower-limb ischemia with concomitant left upper-limb occlusion. Computed tomography angiography showed filling defects in the ascending and descending thoracic aorta. Recurrent embolization after peripheral thromboembolectomy prompted emergency ascending aortic exploration. A friable intramural myxoma was excised with ascending aortic graft replacement; the descending lesion was excluded by staged thoracic endovascular aortic repair while therapeutic anticoagulation was maintained.

Histopathology confirmed an aortic wall myxoma. The case illustrates the limitations of imaging and an individualized hybrid strategy for suspected multifocal aortic involvement.

Recurrent embolization after embolectomy should prompt urgent proximal-source control. Hybrid repair may be considered when anatomy and clinical urgency support it.

Solute carrier family 35 member F2 (SLC35F2) is a transporter located predominantly at the plasma membrane and Golgi apparatus and is predicted to contain ten transmembrane helices. Recent studies have identified SLC35F2 as the only currently known queuosine (Q)-specific transporter in human cells and as the principal high-affinity transporter of queuine (q), although it is not the absolutely exclusive route for q uptake. SLC35F2 is also aberrantly expressed in multiple cancers and has been associated with cell proliferation, migration, invasion, chemoresistance, and ferroptosis regulation. However, the available evidence derives mainly from database analyses, individual cell-based studies, and limited animal experiments and does not yet demonstrate that its tumor-promoting effects directly depend on q/Q uptake or tRNA queuosine modification. SLC35F2 is also an important uptake transporter for the anticancer agent YM155, and its expression can influence intracellular drug exposure and DNA-damage toxicity. YM155 was initially classified as a survivin transcriptional inhibitor, but subsequent studies indicate that its actions also involve DNA intercalation and oxidative DNA damage. Previous clinical trials did not prospectively stratify patients by SLC35F2 expression and showed limited overall efficacy; consequently, its clinical value remains translationally uncertain and biomarker-dependent. Using a structured narrative-review approach, this article critically evaluates the structure and localization of SLC35F2, q/Q transport, regulation of its expression and protein stability, tumor-associated functions, and YM155 delivery. It distinguishes replicated mechanisms from findings supported by single studies and from testable hypotheses, thereby providing a framework for future mechanistic research and precision drug delivery.

AIM: To present cases of spontaneous cerebrospinal fluid (CSF) rhinorrhea and otorrhea, and to conduct a systematic literature review examining the relationship between benign tumor location and the leak side. MATERIAL and METHODS: A PRISMA-based systematic review was conducted to evaluate studies on spontaneous CSF leaks caused by benign intracranial tumors, alongside three newly reported cases. RESULTS: All three cases exhibited CSF leaks ipsilateral to the tumor: Case 1 involved a pituitary ACTH-secreting macroadenoma with rhinorrhea; Case 2, a pineocytoma with hydrocephalus and nasal encephalocele; and Case 3, a petromastoid meningioma with otorrhea. In the systematic literature review, 28 of 125 studies met the inclusion criteria. The median patient age was 42 years, with a male-to-female ratio of 16:12. Macroprolactinoma was the most frequent tumor (25%), primarily located in the sella (46.4%). Tumors were located at the midline (39.3%), right side (35.7%), or left side (25%). The sphenoid sinus was the most common site of CSF leak (39.3%). The leak occurred through the right nostril (39.3%), left nostril (39.3%), both nostrils (10.7%), right ear (7.1%), and both the nostril and ear (3.5%). Hydrocephalus was present in 25% of cases. CONCLUSION: Although our cases demonstrated ipsilateral leaks, the literature review revealed equal rates of left-sided rhinorrhea, even with midline or right-sided tumors, suggesting skull base bone destruction alone does not explain CSF leaks, particularly in benign intracranial tumors outside mastoid involvement. Careful patient history regarding the side of rhinorrhea, comprehensive preoperative imaging, and hydrocephalus evaluation are essential for identifying the leak site and preventing complications, such as recurrent meningitis.

AIM: To examine the selective cytotoxic effects of Electro-Capacitive Cancer Therapy (ECCT) on human glioblastoma (GBM) cell lines (U87-MG and T98-G) and to evaluate its impact on normal epithelial cells. MATERIAL and METHODS: U87-MG and T98-G glioblastoma cells, along with Beas-2B normal epithelial cells, were exposed to ECCT at 100 kHz frequency and 20 V for 24 hours. Cell viability was determined using the MTT assay, while morphological changes were assessed through phase-contrast microscopy. Statistical analyses were conducted using one-way ANOVA and Student's t-test, with statistical significance defined as p < 0.05. RESULTS: ECCT exposure caused a time-dependent reduction in the viability of both GBM cell lines. U87-MG cells showed significant inhibition at all exposure durations, whereas T98-G cells exhibited a marked decrease only after 24 hours (p < 0.0001). In contrast, Beas-2B cells maintained their morphology and viability, suggesting that ECCT selectively targets malignant cells while sparing normal epithelial cells. CONCLUSION: ECCT significantly inhibits glioblastoma cell proliferation without adversely affecting normal cells, highlighting its promise as a non-invasive adjunctive treatment option for GBM. Further preclinical and clinical studies are warranted to clarify its underlying mechanisms, optimize exposure parameters, and determine its potential integration into multimodal glioblastoma therapy.

Bioactivation and clearance of anticancer agents are crucial factors in the efficacy and toxicity of anticancer drugs. Exosomes are membrane-bound vesicles secreted by tumor cells and the tumor microenvironment. These vesicles contain drug-metabolizing enzymes, transporters, and RNA. Exosomes can be non-invasively collected from the blood. This article has been prepared by combining the evidence of the role of exosomal cytochrome P450 isoforms, such as cytochrome P450 family 2 subfamily C member 19, cytochrome P450 family 2 subfamily D member 6, and cytochrome P450 family 3 subfamily A member 5, in the oxidation of anticancer drugs in the first phase of drug metabolism. Exosomal UDP-glucuronosyltransferase 1A1 has been found to help in the conjugation of anticancer drugs in the second phase of drug metabolism. Exosomal ATP-binding cassette transporters, P-glycoprotein, multidrug resistance-associated protein 1, and breast cancer resistance protein have been found to act as intercellular conveyors of drug efflux capacity. These transporters can modulate the efficacy of chemotherapy. Exosomal microRNAs, such as microRNA-21, microRNA-155, and microRNA-1246, have been found to modulate apoptosis, DNA repair, metabolic adaptation, and chemotherapy resistance through the PI3K/AKT pathway, EZH2/STAT3 pathway, and PDCD4 pathway. Long non-coding RNAs, such as UCA1 and HOXA antisense RNA, can reprogram the chromatin structure. These long non-coding RNAs can suppress tumor suppressor genes, thus leading to chemotherapy resistance. Bioinformatics pipelines have been designed to bridge the gap between exosomal RNA and protein levels in the profile of dynamic metabolic states. The challenges in the field of exosomal therapy drug monitoring have been discussed in the article. The article has recommended the use of artificial intelligence in the integration of omics with microfluidic technology for the improvement of exosomal therapy drug monitoring.