Breast cancer (BC) is a major health concern for women, with early diagnosis essential for better health outcomes such as survival. While mammography is the gold standard screening tool, it is not without drawbacks. Circular RNAs (circRNAs), a class of noncoding RNAs, characterized by covalently closed loops missing 5' and 3' ends, offer stability in body fluids like plasma and are emerging as promising diagnostic biomarkers. Thus, the aim of this study was to investigate the plasma levels of hsa_circ_0001785 and hsa_circ_0079876 in BC patients compared to healthy controls to evaluate their potential for noninvasive BC detection.

A total of 129 women participated in this study (81 BC patients who underwent surgery and 48 healthy controls based on mammography). The plasma levels of hsa_circ_0001785 and hsa_circ_0079876 were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) following RNA extraction from plasma samples. The diagnostic value was assessed using the receiver operating characteristic (ROC) curve.

A significant increase in the expression of both circRNAs was observed in BC patients compared with healthy controls (p value < 0.001). ROC curve analysis demonstrated that an area under the curve (AUC) for hsa_circ_0001785, hsa_circ_0079876, and their combination were 0.76 (sensitivity = 74%, specificity = 79%), 0.98 (sensitivity = 93%, specificity = 92%), and 0.98 (sensitivity = 93%, specificity = 92%), respectively.

Plasma levels of hsa_circ_0001785 and hsa_circ_0079876 are significantly elevated in BC patients, with hsa_circ_0079876 showing superior sensitivity and specificity compared to hsa_circ_0001785. These findings highlight hsa_circ_0079876 as a particularly promising diagnostic potential in a case-control setting for noninvasive BC detection.

The relationship between macroscopic tumour morphology and clinical outcomes has previously been demonstrated for malignant melanoma and gastric cancers, but not for anal squamous cell cancer (ASCC). This study investigated the effect of the morphology of ASCC on oncological outcomes.

The morphology of all ASCC patients presenting between 2003 and 2022 was analysed retrospectively and classified as Exophytic, Ulcerated or Mixed. The primary outcome was 5-year overall survival (OS). Secondary outcomes were complete response to treatment, local recurrence (LR) and 5-year disease-free survival (DFS).

Of 622 patients referred to the anal MDT, 515 were included for analysis: 290 exophytic, 179 ulcerated and 46 mixed morphology. Ulcerated morphology was associated with a significantly lower percentage of patients surviving at 5 years compared to exophytic and mixed groups (25.1% vs. 67.9% vs. 65.2% p < 0.001). Ulcerated and mixed morphology patients presented with significantly larger tumours (T4- 30.7% vs. 28.3% vs. 10.0% p < 0.001) and greater nodal involvement (N2- 26.3% vs. 17.2% vs. 15.2% p = 0.042). Exophytic morphology patients had significantly greater complete response at 95.9%, compared to 82.6% for mixed and 45.8% for ulcerated tumours (p < 0.001). Morphology remained significant in both univariable and multivariable Cox regression models across 5-year OS, DFS and LR. Ulcerated [HR 5.160 (3.338-7.979) p < 0.001] and mixed morphology [HR 2.299 (1.179-4.482) p = 0.015] had significantly worse risk of 5-year overall survival compared to exophytic morphology.

Ulcerated morphology is associated with advanced tumours, poor response to chemoradiotherapy, resulting in a higher incidence of recurrent disease and worse overall- and disease-free survival.

Adrenal tumors involve multidisciplinary challenges, including bone health impairment due to mild or fully manifested cortisol overproduction by the adrenal cortex.

We aimed to assess dual-energy X-ray absorptiometry (DXA)-based category switch in non-surgery candidates who were initially diagnosed with non-functional adrenal tumors (NFATs) at computed tomography (CT).

This was real-life setting associated with a longitudinal analysis in menopausal individuals (age range: 50 to 80 years) diagnosed with NFATs who had a central DXA scan at baseline and during monitorization.

malignancies, functional adrenal tumors.

The initial cohort (n=33) included: 21.21% of the patients had osteoporosis (group A), 60.61% had osteopenia (group B) and 18.18% had normal DXA (group C), with similar age and menopause duration, but higher body mass index (BMI) in group C vs. group A (35.33±8.61 vs. 26.82±4.00 kg∕m²; p=0.039). Hormonal and CT-based features were similar among the groups. Group C had higher osteocalcin vs. group B (30.93±14.07 vs. 18.88±8.42; p=0.051). Baseline morning (plasma) cortisol negatively correlated with DXA-bone mineral density (BMD) at femoral neck (r=-0.539, p=0.017). Median follow-up was similar among the groups (50 months, Q1-Q3 quartiles: 24 to 71 months). 66.67% of patients from group C experienced a DXA category switch vs. group B (20.00%; p=0.051). Decrease DXA category switch was more prevalent in group C vs. group A (p=0.021), respectively, group C vs. group B (p=0.013).

Sharpest DXA-BMD decline was between 48 and 72 months. The cumulative probabilities of decrease DXA category switch-free survival were higher in osteopenia vs. normal (p-value log-rank: 0.026), indicating that patients with normal results of DXA-BMD were more likely to decrease category in comparison to the subjects initially confirmed with osteopenia. To our best knowledge, only a limited number of studies longitudinally assessed bone status in NFATs so far.

Ileal neuroendocrine tumors (NETs) are well-differentiated neoplasms with relatively indolent histological features but an often aggressive biological behavior, characterized by early lymphatic and hematogenous dissemination. Increasing evidence suggests that systemic inflammatory and nutritional status may influence tumor progression; however, data regarding these parameters in ileal NETs remain limited.

A retrospective observational study was conducted on 12 consecutive patients with histologically confirmed ileal NETs who underwent surgical treatment between 2018 and 2024. Clinicopathological, morphological, immunohistochemical, and laboratory data were analyzed. Systemic inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, and prognostic nutritional index, were calculated from preoperative blood tests and evaluated in relation to metastatic status.

The cohort comprised predominantly well-differentiated NETs classified as NET G1-G2. Most tumors showed deep wall infiltration and a high prevalence of regional lymph node and distant metastases at diagnosis. Patients with metastatic disease were significantly younger and had lower hemoglobin levels. Higher values of inflammatory indices and lower nutritional markers were consistently observed in the metastatic group, although these differences did not reach statistical significance.

Ileal NETs exhibit a distinct biological behavior in which well-differentiated morphology frequently coexists with advanced disease. Systemic inflammatory and nutritional indices may reflect tumor burden and metastatic potential and could complement histopathological evaluation in the clinical assessment of ileal NETs. Larger prospective studies are warranted to clarify their prognostic value.

Breast cancer (BC) is the most frequently type of cancer diagnosed among women worldwide, according to current epidemiological data. It represents also a leading cause of cancer-related mortality and there are many disparities in stage at diagnosis due to differences among patients' education and access to care. Accurate tissue diagnosis is mandatory to provide best treatment decisions. The positive diagnosis is provided by image-guided core needle biopsy (CNB) that offers adequate tissue for both histopathological (HP) and immunohistochemical (IHC) analysis. The examination of the tissue remains fundamental for establishing tumor subtype and appropriate treatment.

The study evaluates HP and IHC characteristics of BC tumors obtained by CNB in a tertiary care hospital in Bucharest, Romania.

We conducted a retrospective analysis of 39 patients diagnosed with breast tumors at Sf. Ioan Hospital, in Bucharest, between January 2024 and December 2024. Data extracted included tumor laterality, quadrant location, histological type and hormone receptor status. This included estrogen receptor (ER), progesterone receptor (PR), as well as human epidermal growth factor receptor 2 (HER2) status, and the Ki-67 proliferation index (PI). Cases were classified into molecular subtypes. All biopsies were performed on clinically palpable lesions.

Among the 39 biopsies, invasive BC of no special type (NST) represented the predominant malignant subtype. Most tumors were ER-positive and∕or PR-positive, with HER2-negative expression being the leading phenotype. Ki-67 PI values were frequently ≥20%, indicating a high-proliferation profile in a substantial proportion of cases.

This single-center retrospective study provides insight into the distribution of key pathological and molecular features among newly diagnosed BC patients in a Romanian clinic. Our findings highlight the importance of accurate biopsy-based profiling in guiding treatment strategies.

Forkhead box protein M1 (FOXM1) is a pivotal member of the forkhead box family of transcription factors, characterized by its marked overexpression in a wide range of human malignancies and its critical role in driving tumor progression through the regulation of cancer cell proliferation and invasion, making it an attractive target for anti-cancer therapy. However, comprehensive reviews detailing the role of FOXM1 in regulating tumor immunity are still lacking. In this review, we summarize the multiple roles of FOXM1 in regulating tumor immunity and assess its potential as a therapeutic target. FOXM1 plays a crucial role in regulating the tumor immune microenvironment by modulating immune checkpoints, influencing macrophage polarization, and affecting T cell differentiation and infiltration. Furthermore, FOXM1 also plays a regulatory role in key immune-related signaling pathways, including signal transducer and activator of transcription 1 (STAT1) and interferon stimulated gene (STING). Furthermore, the potential of targeting FOXM1 to enhance the efficacy of immunotherapies is discussed, with particular emphasis on overcoming challenges related to immune evasion, neurotoxicity, and therapeutic resistance. This review also summarizes the current landscape of FOXM1-targeted drug development and application, including small molecule inhibitors, peptide-based therapeutics, and combination treatment strategies, highlighting the promising clinical prospects of FOXM1 as a novel and multifaceted target in cancer therapy.

Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy often diagnosed at an advanced stage. For over a decade, gemcitabine-cisplatin (GemCis) remained the standard of care with limited survival benefit. The advent of immune checkpoint inhibitors (ICIs) has transformed the therapeutic landscape, but variability in outcomes and a rapidly expanding evidence base require systematic synthesis.

A systematic review was conducted following PRISMA 2020 guidelines. The review was not registered in PROSPERO or another prospective registry. PubMed/MEDLINE and Embase were searched from inception through 31 December 2024. Studies evaluating PD-1/PD-L1/CTLA-4 inhibitors alone or in combination for advanced CCA were included. Risk of bias was assessed using ROBINS-I for non-randomized studies and Cochrane RoB 2 for randomized controlled trials. A narrative synthesis was performed due to clinical and methodological heterogeneity.

Fifty-one studies (≈ 4,800 patients) met inclusion criteria, including 8 randomized controlled trials and 43 non-randomized studies. First-line chemo-immunotherapy with durvalumab or pembrolizumab plus GemCis established new standards of care in TOPAZ-1 (mOS 12.9 vs. 11.3 months; HR 0.76) and KEYNOTE-966 (mOS 12.7 vs. 10.9 months; HR 0.83). Triplet regimens (chemotherapy + ICI + tyrosine kinase inhibitor [TKI]) demonstrated high activity (e.g., toripalimab + lenvatinib + GEMOX: ORR 80%, mOS 22.5 months). Second-line ICI monotherapy yielded modest ORRs (3-22%), while ICI + TKI combinations showed ORRs of 9-28%. Grade ≥ 3 treatment-related adverse events ranged from 10 to 17% (ICI monotherapy) to 70-75% (chemo-ICI). PD-L1 expression was not predictive in chemo-ICI; homologous recombination deficiency (HRD)/DNA damage response (DDR) mutations and circulating tumor DNA (ctDNA) clearance emerged as promising biomarkers.

ICIs combined with chemotherapy have redefined first-line treatment for advanced CCA. Triplet and locoregional combinations show encouraging efficacy, warranting further validation. Biomarker-driven selection, particularly HRD/DDR status and ctDNA monitoring, will be critical to optimizing outcomes.

The global rise in cancer occurrence, together with the spread of multidrug resistance, highlights the critical demand for innovative treatment strategies. Nano-delivery approaches have emerged as promising solutions that enhance bioavailability and facilitate targeted drug delivery. This study evaluated the anticancer efficacy of Nepeta glomerulosa extract and its silver-loaded nanoemulsion (Ag-N.g.Ext. NEs) against human lung (A549) and gastric (AGS) cells.MethodsNepeta glomerulosa was collected from the Binaloud Mountains, and a hydroalcoholic extract was obtained by maceration. Ag-N.g.Ext. NEs were prepared via high-energy emulsification and characterized by FTIR, SEM, DLS, ZP, and XRD. Cytotoxicity and apoptosis were assessed using MTT assay, DAPI staining, and Real-time PCR of TP53 and BAX genes.ResultsAg-N.g.Ext. NEs were spherical (confirmed by SEM) with a PSA (DLS) size of 269.5 nm, a negative zeta potential of -23.1 mV, and a non-crystalline structure. The IC₅₀ of the extract for A549 and AGS was 500 and 250 µg/mL, while the Ag-N.g.Ext. NEs showed enhanced potency with an IC₅₀ of 125 µg/mL. Apoptosis and gene expression were significantly higher in Ag-N.g.Ext. NEs-treated cells (p ≤ 0.05). TP53 expression increased 3.317-fold in A549 and 8.027-fold in AGS; BAX increased 3.877-fold in A549 and 2.351-fold in AGS.ConclusionsNanoemulsion-based delivery significantly enhances the anticancer efficacy of the extract by promoting apoptosis, offering a promising strategy for plant-derived therapeutics.

Programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors are foundational components of therapy across many solid tumors, yet primary and acquired resistance limit durable benefit for a substantial proportion of patients. Rather than attempting a broad survey of every disease area, this review deliberately focuses on three tumor types in which PD-(L)1-based combinations have generated the most mature, practice-relevant evidence and in which the field is evolving most rapidly: renal cell carcinoma (RCC), urothelial (bladder) cancer, and non-small cell lung cancer (NSCLC). For each, we examine how combinations are being developed and positioned across the advanced, adjuvant, and neoadjuvant/perioperative settings, and we place selected cross-cutting strategies (dual checkpoint blockade, antibody-drug conjugates, hypoxia-inducible factor [HIF]-2α inhibition, and other partners) in that disease-specific context.

In RCC, immune checkpoint inhibitor (ICI) plus vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) doublets are established first-line standards, adjuvant pembrolizumab is the first agent to improve both disease-free and overall survival after nephrectomy, and the HIF-2α inhibitor belzutifan has become a post-ICI/TKI option while being tested earlier in disease. In bladder cancer, the antibody-drug conjugate enfortumab vedotin combined with pembrolizumab has displaced platinum chemotherapy as first-line therapy for advanced disease, and perioperative durvalumab added to neoadjuvant chemotherapy improves event-free and overall survival in muscle-invasive disease. In NSCLC, neoadjuvant and perioperative chemoimmunotherapy regimens now demonstrate overall survival benefit, complementing established advanced-disease and adjuvant strategies. We also summarize combinations that have failed-most notably concurrent PD-(L)1 blockade with EGFR or ALK TKIs in oncogene-driven NSCLC, and anti-TIGIT antibodies in phase III-because these negative results are as instructive as the successes. Within RCC, bladder cancer, and NSCLC, next-generation PD-(L)1 combinations are reshaping treatment across all disease stages. The magnitude of benefit, the relevant biomarkers, and the toxicity trade-offs differ substantially by tumor type and by setting. Successful development depends on a sound biologic rationale, biomarker-informed patient selection, and careful toxicity management, and the evidence base remains uneven-ranging from mature phase III data to early signals-which we make explicit throughout.

Karyopherin subunit alpha 2 (KPNA2) has been implicated in a variety of human diseases, particularly cancer. This study aimed to elucidate the role of KPNA2 in the development and progression of gastric cancer (GC). Bioinformatics analyses revealed that KPNA2 expression was significantly higher in GC tissues, and qRT-PCR, western blotting, and immunohistochemistry subsequently validated these findings. To establish a clearer connection between bioinformatics findings and functional validation, in vitro experiments were performed in GC cell lines, in which silencing of KPNA2 significantly inhibited cell proliferation, migration, and invasion. These inhibitory effects were further confirmed in mouse xenograft models. KPNA2 depletion impaired DNA replication, induced S-phase cell cycle arrest, and significantly enhanced apoptosis in GC cells. Molecular analyses further demonstrated that KPNA2 downregulation suppressed β-catenin signaling pathway activation and inhibited epithelial-mesenchymal transition. These results suggest that KPNA2 facilitates GC cell proliferation, cell cycle progression, resistance to apoptosis, and metastatic behavior by activating the β-catenin/EMT axis. Therefore, KPNA2 may serve as a potential therapeutic target for gastric cancer.