Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options, driven in part by its immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) and neutrophils (TANs) contribute to tumor progression and immune evasion. A Disintegrin and Metalloproteinase 8 (ADAM8), a zinc-dependent protease, is strongly upregulated in PDAC and correlates with poor clinical outcomes, suggesting a regulatory role in tumor progression.

Wild-type (WT) and Adam8 knockout (A8KO) PDAC cell lines were generated using the CRISPR-Cas9 technique, and PDAC mouse models with or without Adam8 expression were established to investigate the role of ADAM8 in tumor and immune cells. In vitro assays, including Western blotting, qPCR, migration and invasion assays, proliferation assays, ELISA, cytokine and proteome analyses, as well as co-culture experiments with PDAC cells and either macrophages or neutrophils, were employed to assess the effects of ADAM8 on tumor-immune cell crosstalk. In parallel, in vivo WT and A8KO KPC models were generated, genotyped, and monitored to evaluate the impact of ADAM8 on survival, tumor growth, and immune cell recruitment within the PDAC TME.

ADAM8 deletion reduced tumor cell proliferation and migration, associated with reduced activation of FAK/Src/STAT3 signaling and altered secretion of cytokines including GM-CSF, M-CSF, ICAM-1, and TNF-α. Co-culture assays demonstrated that ADAM8 enhanced reciprocal signaling between tumor cells and TAMs/TANs, promoting pro-oncogenic activation. Migration assays and in vivo analyses revealed that ADAM8 facilitated recruitment of macrophages and neutrophils in PDAC TME, while Adam8KO tumors exhibited reduced immune infiltration and altered macrophage polarization.

Our findings demonstrate that ADAM8 promotes PDAC aggressiveness by enhancing tumor cell proliferation and migration, activating FAK/Src/STAT3 signaling, and driving macrophage and neutrophil recruitment through cytokine regulation. By orchestrating both tumor-intrinsic pathways and tumor-immune interactions, ADAM8 emerges as a key determinant of PDAC progression and a systemic target for therapeutic intervention.

Medullary thyroid carcinoma (MTC) is characterized by frequent RET mutations, while non-RET alterations remain less well studied. Previous reports have identified a recurrent STK11 c.1062 C > G (p.Phe354Leu) variant in MTC, but its clinicopathologic and functional significance remains uncertain.

A total of 129 MTCs (128 families) were analyzed by Sanger sequencing to screen for the STK11 c.1062 C > G variant. Germline status was assessed in cases with available normal tissue. Targeted next-generation sequencing was performed in 30 tumors (29 families). Functional effects of the STK11 c.1062 C > G variant were evaluated using an overexpression model in TT cells, with assessment of AMPKα phosphorylation. Progression-free survival was analyzed using Kaplan-Meier methods.

The STK11 c.1062 C > G variant was identified in 12 of 129 MTCs (9.3%) and in 11 of 128 families (8.6%). It was significantly enriched in hereditary cases compared with sporadic tumors: 27.8% (5/18) vs. 7.7% (1/12) for individual MTC cases, and 23.5% (4/17) vs. 7.7% (1/12) for families. In evaluable cases, the variant was confirmed to be germline. Tumors harboring STK11 c.1062 C > G showed a mutational spectrum predominantly involving RET, whereas variant-negative tumors exhibited more heterogeneous alterations, including genes related to DNA repair and chromatin remodeling. No significant difference in progression-free survival was observed between groups (P = 0.54). In vitro, the STK11 c.1062 C > G variant was associated with reduced AMPKα phosphorylation compared with wild-type STK11.

Given the population frequency and ClinVar benign/likely benign classification of this variant, our data do not support STK11 c.1062 C > G as a primary driver of MTC; rather, it may represent a recurrent germline variant that could act as a low-penetrance modifier in a subset of patients, warranting cautious interpretation and further validation.

To evaluate the associations between transcription factor (TF)-defined molecular lineages and the clinical characteristics of pituitary neuroendocrine tumors (PitNETs).

A retrospective cohort analysis was performed in 274 patients who underwent extra-pseudocapsular transsphenoidal resection. Tumors were classified by TF-defined lineage and invasion grade (0-3) and Knosp score. Group differences were tested, and predictors of gross total resection (GTR) were examined using hierarchical multivariable logistic regression.

TF-defined lineage classification improved diagnostic precision. Among tumors with an immunonegative hormone profile, 74.7% received a definitive lineage assignment. The pituitary transcription factor 1-growth hormone/prolactin (PIT1-GH/PRL) subgroup had the highest incidence and grade of invasion; SRY-box transcription factor 2 (SOX2) positivity was most frequent in this subgroup (41.7%), which also exhibited the lowest GTR rate (58.3%). SOX2-positive tumors were associated with significantly higher preoperative adrenocorticotropic hormone (ACTH) (median: 38.80 vs. 31.60 pg/mL, P = 0.032) and GH (median: 1.12 vs. 0.43 ng/mL, P = 0.046) levels. SOX2 positivity was 20.5% in multilineage tumors and 20.0% in the recurrent cohort (n = 20). Compared with Trouillas grade alone, the combination of invasion grade and intraoperative features (capsule status and vascularity) significantly improved the ability to predict GTR (AUC, 0.866 vs. 0.795; ΔAUC = 0.071; DeLong 95% CI, 0.022-0.120; P = 0.005).

The 2022 WHO TF-defined lineage system improves diagnostic precision and facilitates the interpretation of PitNET differentiation and molecular pathology. Tumors in the PIT1-GH/PRL subgroup demonstrate more aggressive invasive features. SOX2 positivity was relatively frequent in multilineage tumors, whereas the observation in recurrent cases was limited by the small exploratory cohort and requires validation in larger longitudinal studies.

Currently, no established guidelines exist for dosing chemotherapy or immunotherapy in patients with achondroplasia.

A 69-year old female with congenital achondroplasia was diagnosed with stage IV non-small cell lung carcinoma type adenocarcinoma, with high Tumor Mutational Burden and 20% programmed death-ligand 1 expression. The patient received carboplatin dose based on renal function utilizing measured creatinine clearance, pemetrexed based on body surface area and pembrolizumab at a fixed dose of 100mg for body weight <65 kg. The doses of carboplatin and pemetrexed were adjusted after the first cycle based on therapeutic drug monitoring (TDM). The treatment was generally well tolerated, with the exception of grade 2 neutropenia, which resolved after a one-week delay of the third treatment cycle. A favorable clinical response was achieved after four treatment cycles.

Given the uncertainty regarding the accuracy of dosing algorithms in patients with congenital achondroplasia, TDM may support dose optimization and attainment of adequate drug exposure.

Dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, plays an important role in the metabolism of fluoropyrimidine (FP) drugs, including tegafur, in S-1. A decrease in DPD activity can cause severe FP-related toxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for FP and DPYD polymorphisms recommend FP dose adjustments based on the four major DPYD polymorphisms. However, multiple rare variants of DPYD have been reported. We present the case of a man in his 50s with cT3N0M0 tongue squamous cell carcinoma who developed severe myelosuppression and diarrhea after the initiation of S-1 (tegafur/gimeracil/oteracil) despite appropriate dosing. On day 20 of treatment, the patient developed grade 4 neutropenia and septic shock and required ICU admission. Genetic testing identified a rare heterozygous DPYD variant (c. 812delT) that causes a frameshift and a presumed loss of enzyme function, suggesting an underlying cause of the severe adverse events. Although severe toxicity occurred, marked tumor shrinkage allowed for less invasive surgery. This case highlights the need for expanded genetic screening beyond the guideline-listed variants, particularly in Asian populations, where common variants differ. Combining genotypic and phenotypic evaluations of DPD activity may improve the prediction and prevention of FP-related toxicities, supporting safer and more effective use of FP drugs.

Pelvic lymph-node dissection (PLND) during robot-assisted radical prostatectomy (RARP) is important for nodal staging, but its optimal extent, morbidity profile, and integration with precision-guided techniques remain unsettled. This study mapped the knowledge structure and thematic evolution of RARP-associated PLND research. A single-database search of the Web of Science Core Collection was performed for English-language articles and reviews formally published through 2025. Two reviewers independently screened records directly evaluating PLND, nodal staging, lymphatic morbidity, or related preventive and guidance strategies during RARP according to predefined eligibility criteria. Bibliometrix, VOSviewer, CiteSpace, and Scimago Graphica were used to assess publication trends, collaboration patterns, citation structure, and keyword evolution. The final dataset comprised 225 eligible records, including 208 original research articles and 17 review articles published during 2006-2025. Output increased markedly after 2019 and peaked at 27 publications in 2024. The United States received the most citations, whereas the Netherlands Cancer Institute was the most productive institution. van der Poel H.G. was the most productive author. The knowledge base initially focused on PLND templates, anatomical extent, and lymph-node yield, then expanded toward risk-adapted nodal staging, oncologic implications, lymphatic morbidity, and precision-guided nodal assessment. Keyword analysis identified eight thematic clusters and showed recent attention to peritoneal flap and fixation strategies, node-positive disease, and image- or radioguided nodal approaches. This bibliometric analysis characterizes a shift in RARP-associated PLND research from surgical extent and staging yield toward individualized selection, morbidity reduction, and precision-guided nodal strategies. Further prospective studies are needed to clarify how preventive reconstruction and targeted nodal techniques should be integrated with anatomically defined extended PLND.

Osteosarcoma (OS) is the most common bone cancer, known for its aggressive nature, high chemoresistance, and strong metastatic potential responsible for poor clinical outcomes. In this context, identifying reliable biomarkers and therapeutic targets is therefore critical. This study investigates the role of paraoxonase-2 (PON2), an intracellular enzyme known for its anti-oxidative and anti-apoptotic properties. PON2 overexpression has been observed in various cancers and is implicated in tumor development and progression.

PON2 expression was evaluated by immunohistochemistry in bone tissue samples from OS patients and control subjects. shRNA-mediated PON2 silencing was performed in U-2 OS and Saos-2 cells to assess proliferation, viability, migration, chemosensitivity, ROS production, apoptosis activation, glucose uptake, and GLUT1 expression. PON2 overexpression and N-acetylcysteine (NAC) pre-treatment in CDDP-treated U-2 OS cells were used as rescue approaches. Preliminary analyses showed markedly higher PON2 expression in OS than in control bone specimens. PON2 knockdown reduced proliferation, viability, and migration, while enhancing sensitivity to cisplatin (U-2 OS and Saos-2) and doxorubicin (U-2 OS only); these effects were reversed by PON2 upregulation. PON2 silencing also increased ROS levels and caspase expression, and impaired glucose uptake by reducing GLUT1 expression and intracellular glucose levels. Since NAC did not fully rescue these alterations, PON2 appears to sustain chemoresistance by affecting important mechanisms related to ROS detoxification, glucose metabolism, and anti-apoptotic signaling.

Obtained data clearly illustrate the potential of PON2 as promising biomarker and molecular therapeutic target for human OS.

Monodispersed highly magnetic iron oxide nanocubes and nanospheres with magnetization (78.72 emu/g_cubic and 72.08 emu/g_sphere with an average size of 17.45 ± 5.13 nm for spherical (IONPs) and with edge lengths ranging from 20.85 ± 6.60 nm for nanocubes (IONCs) have been successfully synthesized and functionalized with methoxy-polyethylene glycol (m-PEG). The specific absorption rate (SAR) has been observed to be 351.5 W/g for IONPs and 415.06 W/g for the IONCs. The antimicrobial activity of the synthesized nanoparticles (NPs) against Staphylococcus aureus and Escherichia coli was evaluated using the agar well diffusion method. Anti-angiogenic effects were evaluated via the Chick Chorioallantoic Membrane (CAM) assay, an extensively used in vivo model. Additionally, m-PEG-coated IONCs were functionalized with doxorubicin (DOX) and the tumor-targeting aptamer AS1411 to enable targeted magneto-chemotherapy (MCT) in 3D breast cancer models. The results show that magneto-chemotherapy (MCT) reduces cancer cell viability to 76.41% in 2D cultures and 77.27% in 3D cultures, highlighting the potential of 3D models for enhancing the effectiveness of targeted therapies in breast cancer.

Deep-learning neural network algorithms for detecting prostate cancer in MRI have proliferated in the literature. However, out of 30+ studies published since the PROSTATEx challenge, no studies tested the performance of their algorithm against using true external image data sets (studies came from an outside institution that did not supply any training data to the algorithm) while validating against MR-US fusion biopsy or whole-mount prostatectomy. Using true external data sets paints a much clearer picture of real-world clinical performance of an algorithm.

This work will assess the performance of a published deep learning (DL) neural network algorithm to detect prostate cancer using external studies. The main difference from other studies is the combination of using only MR-US fusion biopsy results as a gold standard; using test data from an institution that did not supply any training data for this version of the algorithm (including studies acquired with an endorectal coil, which were not in the original training set); and comparing the performance of algorithm-generated regions-of-interest (ROIs) versus algorithm heat maps.

Patients were included in the study if they had a prostate MRI with at least one radiologist-drawn target on MRI and underwent MR-US fusion biopsy where the target was sampled for pathological analysis. Patients were excluded if they had any history of prostate cancer treatment, had previously undergone MR-US fusion biopsy at our institution, were missing MRI acquisitions, had artifacts in image sets, or if the study had been shared for future algorithm development. MR image data was assessed using a DL research prototype (XProstate) from Siemens Healthineers that produced (a) ROIs in suspected cancer areas with a level of suspicion (LoS) score and (b) heat maps with LoS scores across the entire gland. The XProstate prototype had been trained with 2170 studies from eight different academic institutions. Clinical radiologist, XProstate ROI, and XProstate Heat Map scores were assessed with ROC analysis using pathology results from biopsy as a gold standard.

202 unique patients were included for assessment of the XProstate research prototype. The ROC curve for the XProstate Heat Map LoS score generated the highest AUC (0.76, 95% CI: 0.70, 0.82) followed by clinical radiologist PI-RADS score (0.73, 95% CI: 0.68, 0.79) and by XProstate ROI LoS score (0.71, 95% CI: 0.65, 0.77). Neither the XProstate Heat Map (AUC difference = 0.03, 95% CI: -0.04, 0.10, p = 0.38) nor the XProstate ROI (AUC difference = -0.02, 95% CI: -0.09, 0.04, p = 0.43) was significantly different from the radiologist PI-RADS score.

The XProstate prototype demonstrated equivalent performance as clinical radiologists when presented with de novo cases that would mirror a real-world clinical deployment. The automatic ROI delineation more closely matched clinical radiologist performance when using a cutoff of PI-RADS 5 for annotating suspicious regions. Overall, the XProstate prototype provided reasonable clinical performance and this study demonstrated the need to assess Deep Learning prototypes with external institutional test data.

The NOTCH1 gene and its signaling pathway play a critical role in the oncogenesis and progression of various carcinomas through complex cellular and molecular mechanisms. This integrative literature review examines 21 selected studies across multiple carcinoma types, including head and neck, prostate, penis, breast, and hepatocellular carcinomas, to elucidate the functional impact of notch1 alterations on tumor behavior and clinical outcomes. NOTCH1 functions as a context-dependent regulator, acting either as an oncogene or tumor suppressor according to cellular environment and molecular context. Aberrations in notch1 signaling influence cell proliferation, differentiation, apoptosis, and angiogenesis, thereby contributing to cancer initiation and progression. Despite some variability in findings, the majority of studies indicate that notch1-related molecular changes have significant implications for prognosis and potential therapeutic targeting. This review highlights the importance of understanding notch1 signaling pathways in the cellular and molecular biology of carcinomas, aiming to pave the way for novel diagnostic and treatment strategies.