Myeloproliferative neoplasms (MPNs), encompassing polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are hematologic malignancies characterized by recurrent somatic mutations. Despite advances in next-generation sequencing (NGS), the genetic basis of thrombotic risk and bone marrow (BM) fibrosis in MPNs remains unclear.

Patients diagnosed with classical MPN at Trakya University Faculty of Medicine were retrospectively analyzed (2018-2025). Mutation profiling was conducted on BM aspirates using a 78-gene panel on the Illumina NextSeq platform, with clinically relevant variants (VAF ≥ 2%) interpreted via Qiagen Clinical Insight.

Among 91 patients with MPN, the most frequent mutations were JAK2 (71.4%), TET2 (23.1%), DNMT3A (15.4%), ASXL1 (11%), and splicing factor mutations (SFMs; 12%). Arterial events occurred in 45.1% of patients and were associated with age (p < 0.001), higher Charlson Comorbidity Index (CCI; p < 0.001), ASXL1 (p:0.019), and SFMs (p:0.009). VTE occurred in 38.5% and was associated with JAK2 status and allele burden (p:0.004 and p:0.012 respectively), TET2 (p < 0.001), and SFMs (p:0.002); the JAK2/TET2 co-mutant subgroup had the highest risk of VTE risk in multivariable analysis (OR: 2.9, 95% CI: 1.4-5.7; p:0.002). Advanced BM fibrosis was associated with SFMs (p:0.018). Increased mutational burden correlated with both venous and arterial thrombosis (p:0.021 and p:0.044, respectively). In survival analyses, SFMs (HR: 5.2; p:0.008), ASXL1 (HR: 3.8; p:0.030), and PMF diagnosis (HR: 3.8; p:0.045) were associated with inferior overall survival (OS).

Molecular profiling may provide clinically relevant thrombotic risk stratification in classical MPNs. JAK2/TET2 co-mutation was linked to VTE, while ASXL1 and SFMs were associated with adverse phenotypes including vascular events, BM fibrosis, and inferior OS.

To explore the role of miR-593-5p targeting Polo-like kinase 1 (PLK1) in regulating biological behaviors of human gastric cancer (GC) cells.

Four GC cell lines (MGC-803, AGS, HGC-27, and MKN-45) and normal human gastric mucosal epithelial GES-1 cells were examined for miR-593-5p and PLK1 expressions using RT-PCR, and MGC-803 cells with the lowest miR-593-5p expression and MKN-45 with highest miR-593-5p expression were selected for subsequent experiments. TargetScan7.2 was used to predict the binding between miR-593-5p and PLK1. MGC-803 cells were transfected with miR-593-5p mimic or mimic NC via liposome, and MKN-45 cells were transfected with miR-593-5p inhibitor or inhibitor NC. The changes in cellular PLK1 protein expression levels were detected using Western blotting, and the changes in biological behaviors of the cells were evaluated using scratch assay, Transwell assay, CCK-8 assay, and flow cytometry.

Compared with GES-1 cells, the GC cell lines showed significantly downregulated miR-593-5p and upregulated PLK1 expressions. TargetScan7.2 identified binding sites between miR-593-5p and PLK1 3'UTR. In MGC-803 cells, miR-593-5p overexpression caused significant reduction of PLK1 protein expression, inhibited cell migration, invasion, and proliferation, and promoted cell apoptosis. Conversely, miR-593-5p inhibition in MKN-45 cells upregulated PLK1 expression, enhanced cell migration, invasion, and proliferation, reduced cell apoptosis.

miR-593-5p overexpression inhibits GC cell migration, invasion, and proliferation, and promotes apoptosis, likely by directly downregulating PLK1, suggesting the role of miR-593-5p as a tumor suppressor in GC and its potential therapeutic relevance.

To develop a hollow Cu₉S₈-based nanoparticles loaded with the photosensitizer IR780, investigate its photothermal and photodynamic (PTT-PDT) effects against esophageal cancer cells and analyze the underlying mechanisms.

Hollow Cu₉S₈ nanoparticles were synthesized using a sacrificial-template strategy, and IR780 was encapsulated within a lauric acid matrix to serve as a phase-change material for preparing IR780@Cu₉S₈ composite nanoparticles. The composite nanoparticles were characterized for morphology and structural attributes using transmission electron microscopy, X-ray diffraction, and UV-visible spectroscopy. The effects of IR780@Cu₉S₈ on proliferation, invasion, and migration of esophageal cancer cells under near-infrared (NIR) irradiation (808 nm, 1.5 W/cm², 5 min) were assessed using CCK-8 assay, live/dead staining, reactive oxygen species, mitochondrial membrane potential assay, wound-healing assay, and Transwell assay. The in vivo PTT-PDT therapeutic efficacy and biosafety of IR780@Cu₉S₈ was evaluated in a mouse model bearing subcutaneous esophageal cancer xenografts.

The synthesized IR780@Cu₉S₈ nanoparticles exhibited a uniform quasi-spherical morphology with a photothermal conversion efficiency of 44.0%. Under NIR irradiation, IR780@Cu₉S₈ produced pronounced synergistic PTT-PDT effects against KYSE150 cells, causing a significant reduction of cell viability and marked suppression of cell proliferation, migration, and invasion. In the tumor-bearing mice, IR780@Cu₉S₈ and 808 nm laser irradiation exhibited strong synergistic PTT-PDT effects and significantly inhibited tumor growth with a good biocompatibility.

The IR780@Cu₉S₈ composite nanoparticles achieve synergistic PTT-PDT antitumor activity in esophageal cancer cells which can be a promising strategy for combined therapy and targeted drug delivery for esophageal cancer.

To investigate the regulatory role and mechanism of long non-coding RNA LASTR in progression of head and neck squamous cell carcinoma (HNSCC).

LASTR expression in HNSCC and its correlation with patient prognosis were analyzed using TCGA and GEO transcriptomic data, and its expression in HNSCC cell lines was validated by qPCR. In a loss-of-function HNSCC cell model with siRNA-mediated LASTR knockdown, the changes in cell proliferation, migration, and invasion were assessed by high-content counting, CCK-8 assay, ATP detection, and Transwell assay. Bioinformatic analysis was conducted to identify the target genes of LASTR, and their interactions with BCAM were verified by qPCR and immunoblotting. The LASTR-miR-4476-BCAM regulatory axis was confirmed with RNA pulldown and dual-luciferase assays. The functional role of BCAM was investigated, and rescue experiments were performed to determine if BCAM mediates the effects of LASTR expression modulation.

LASTR was significantly upregulated in HNSCC tissues and cell lines, and its high expression was significantly correlated with poor patient prognosis. In HNSCC cells, LASTR knockdown significantly suppressed cell proliferation, migration, and invasion. Bioinformatic analysis revealed 78 candidate target genes of LASTR, enriched in pathways involving angiogenesis, hypoxia response, MAPK, ErbB, and Ras signaling. LASTR knockdown obviously decreased BCAM expression HNSCC cells. Mechanistically, LASTR upregulated BCAM by sequestering miR-4476. BCAM knockdown similarly suppressed malignant phenotypes of HNSCC cells, and its overexpression rescued the inhibitory effects of LASTR knockdown.

LASTR is upregulated in HNSCC and associated with poor prognosis. High expression of LASTR promotes HNSCC progression by acting as a ceRNA for miR-4476 to upregulate BCAM, suggesting the role of LASTR and BCAM as potential biomarkers and therapeutic targets for HNSCC.

This report on neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, highlights the diversity of clinical manifestations associated with this condition. In addition to the predominant neurological symptomatology, this work also reveals the rarer involvement of the gastrointestinal tract in the form of an associated gastrointestinal stromal tumor (GIST). NF1 is an autosomal dominant genetic disorder with multisystem involvement, most commonly affecting the nervous system, skin, and skeleton. In approximately 7% of patients with NF1, a GIST may develop, representing the most frequent intestinal manifestation of neurofibromatosis.

The case of a female patient with genetically confirmed and previously known NF1 initially presented with vertigo, anemia, and melena, ultimately leading to the diagnosis of a bleeding GIST. The tumor was confirmed only through histological examination following intestinal resection.

In patients with NF1, GIST typically presents as multifocal disease with distinct biological behavior and absence of classical mutations. The primary treatment is surgical resection, indicated based on symptoms or tumor size. Hemorrhage from GIST represents both a diagnostic challenge and a serious complication, which could be mitigated through targeted surveillance, facilitating earlier detection and optimal timing of intervention.

Despite the establishment of combined local and systemic therapy as the standard approach for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), its efficacy remains constrained by two primary challenges: the immunosuppressive tumor microenvironment (TME) and treatment resistance. Recent research shows that factor Xa (FXa) boosts programmed death-ligand 1 (PD-L1) expression in tumor cells via the proteinase-activated receptor-2 (PAR-2) and signal transducer and activator of transcription 2 (STAT2) pathways, aiding immune evasion. Rivaroxaban, an FXa inhibitor, prevents portal vein thrombosis and disrupts the FXa/PAR-2/PD-L1 axis, restoring T cell function. Based on this mechanism, we propose that incorporating rivaroxaban as a core adjuvant into a long-term, 'local-targeted-immune' multimodal strategy can spatiotemporally reprogram the TME in advanced HCC with PVTT. This approach has the potential to effectively overcome treatment resistance and achieve sustained disease control. The hypothesis is readily testable in clinical trials, and if substantiated, it could establish a new treatment paradigm aimed at improving the prognosis for this high-risk patient population. Furthermore, it would provide a robust theoretical rationale and practical guidance for advancing the treatment of advanced HCC with PVTT.

Solitary bone metastases represent a major clinical challenge. Surgical metastasectomy remains a valid option in selected patients. This study evaluated the oncologic and functional outcomes following metastasectomy in a cancer referral center in Bogotá, Colombia.

A retrospective observational study including patients with solitary bone metastases who underwent metastasectomy between January 2004 and March 2024. Demographic, clinical, and surgical data were collected. Postoperative functionality was assessed using the MSTS score. Local recurrence, disease progression, and survival were analyzed with a minimum follow-up of 12 months. Kaplan-Meier and log-rank tests were used when appropriate.

Thirty patients (73.3% female) were included, with a mean age of 60.4 ± 10.9 years. The most common primary tumors were renal (26.7%) and breast (16.7%). The predominant surgical technique was endoprosthetic reconstruction (50%). Postoperative complications occurred in 40% (12/30), mainly infections (41%). Among 13 patients with recorded functionality, the moderate MSTS category was most common (53.8%), with no significant associations found with the evaluated clinical or surgical variables (all p > 0.05). During follow-up, 19 patients (63%) developed metastatic progression, 2 (6.7%) developed local recurrence, and 11 (36.6%) remained progression-free. The overall survival rate at 12 months was 65%, with a median follow-up of 12 months (IQR: 12-36).

Metastasectomy in patients with solitary bone metastases appears to be a feasible and safe approach, associated with favorable functional outcomes and low rates of local recurrence in this cohort. Its role should be considered within a multidisciplinary context in carefully selected patients.

B-cell prolymphocytic leukemia (B-PLL) is a rare B-cell neoplasm that presents splenomegaly, lymphocytosis, minimal or absent lymphoadenopathy, at least 55% of prolymphocytes in peripheral blood and a variable clinical course. Complex/composite karyotype and recurrent structural variants (SVs), including TP53 aberrations (mutations/deletion) and MYC abnormalities (translocation or gain) are genetic features typically seen in B-PLL. We applied the genome-wide technology of optical genome mapping (OGM) in 3 cases with B-PLL, finding multiple genomic aberrations, including SVs, copy number variations (CNVs) and aneuploidies. MYC aberrations were not observed in our cases, whereas all B-PLL showed concomitant deletion 17p and TP53 mutations. TP53-disrupted B-PLL cells showed additional genomic alterations that affect genes implicated in extrinsic and intrinsic apoptotic pathways i.e., TNFRSF10, FAS, MDM2, BCL2, and BCL2L11 and genes involved in cell-cycle regulation i.e., IKBKB, CDK2, CDK4, and RB1, suggesting that a convergent multifactorial pathogenetic mechanism may be involved in B-PLL. Applying the OGM technology on cytogenetically complex rare hematological neoplasia may be useful to improve the genetic definition and differential diagnosis of B PLL/SBLPN and related splenic B cell neoplasms.

The Mediterranean diet (MD), characterized by high consumption of plant-based foods, olive oil, moderate intake of fish and poultry, and limited red and processed meats, has been associated with various health benefits, but its role in cancer prevention remains under debate.

This review was conducted in accordance with PRISMA 2020 and MOOSE guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Library was performed up to February 28, 2024. Study quality was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence was evaluated with the NUTRIGRADE approach. Pooled effect sizes were computed using a random-effects model and expressed as risk ratios (RR), hazard ratios, or odds ratios, as appropriate.

A total of 126 studies, including more than 8 million participants, across all included studies, were included. High adherence to the MD, as one point increase in the adherence, was significantly associated with a modest reduced risk of several site-specific cancers, including head and neck (RR = 0.88, 95% CI 0.78-0.98), oral cavity (RR = 0.83, 95% CI 0.73-0.95), stomach (RR = 0.93, 95% CI 0.88-0.97), liver/gallbladder (RR = 0.94, 95% CI 0.93-0.96), colorectal (RR = 0.95, 95% CI 0.92-0.98), bladder (RR = 0.96, 95% CI 0.92-0.995), and breast cancer (RR = 0.95, 95% CI 0.92-0.98). Higher adherence was also associated with lower cancer-related mortality (RR = 0.97, 95% CI 0.96-0.99). Certainty of evidence was rated as moderate for the main outcomes.

Greater adherence to the MD is associated with a lower risk of several site-specific cancers and reduced cancer mortality. These findings support the promotion of the MD as a preventive dietary strategy within public health policies.