Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its highly immunosuppressive tumor microenvironment (TME), which fuels metastasis and resistance to immunotherapy. Through comprehensive analysis of single-cell RNA sequencing datasets, we identified multiple heterogeneous tumor-associated macrophage (TAMs) subpopulations as key regulators of PDAC progression, which coexpress MRC1 and exert their effects by actively suppressing antitumor immune responses. To overcome this barrier, we developed a spatiotemporal macrophage reprogramming platform that leverages STING phase separation to reprogram TAM plasticity and reshape the immune landscape. This system, MRC1-targeting peptide-M@BLZ945 (PMMB), integrates a colony-stimulating factor 1 receptor (CSF-1R) inhibitor and a STING agonist within a macrophage-mimetic nanostructure, enabling sequential, controlled reprogramming of TAMs. By leveraging STING phase separation, PMMB stabilizes TAMs in an antitumor CD80+ phenotype while preventing excessive inflammation, achieving durable immune activation. In preclinical models, PMMB not only suppresses both primary and metastatic PDAC but also enhances CD8+ T cell infiltration, reinvigorates anti-PD-1 therapy responses, and mitigates immune exhaustion. These findings establish spatiotemporal macrophage circuit engineering via STING phase separation as a cross-scale strategy to override PDAC's immune barriers and drive next-generation macrophage-targeted immunotherapy. This study paves the way for rationally designed, precision macrophage modulation strategies in solid tumors.

Prostate cancer (PCa) is the second most diagnosed cancer and the fifth leading cause of cancer death among men worldwide. Androgen receptor (AR), as a ligand-activated transcription factor, is important for both prostate development and PCa progression. Understanding the molecular mechanisms of prostate carcinogenesis has led to the development of therapeutic strategies targeting AR. Inhibiting AR is currently the gold standard for hormone therapy. However, eventually resistance to therapy occurs. The activation of AR by supraphysiological androgen levels (SAL) used currently in clinical trials paradoxically also inhibits PCa progression and induces cellular senescence. Interestingly, circadian rhythm controls hormone biosynthesis including androgens. Intriguingly, SNPs in several clock genes have been associated with PCa risk linking increased cancer risk with day-night shifts. Here, we discuss whether the efficacy of hormone therapeutics depends on the biological clock. It emerges that androgens control the expression of clock genes also intersecting with SAL-induced cellular senescence suggesting a complex and understudied network that governs PCa progression. This review highlights the multifaceted roles of AR signaling in PCa, emphasizing its ability to promote cellular senescence by AR-targeted therapy via genomic and non-genomic pathways and crosstalk with the regulation of circadian clock genes. The intricate interplay between circadian rhythm, androgen signaling, and cellular senescence presents a promising yet underexplored research area in PCa and suggests a multilayered regulatory network that could shape PCa progression and treatment outcomes. Unraveling this network may uncover novel chronotherapeutic strategies and provide new insights into disease, prognosis, and therapy options.

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by rapid proliferation, therapy resistance, and extensive invasion, largely driven by epithelial-mesenchymal transition (EMT). Longikaurin A (LK-A), a natural kaurane diterpenoid, has demonstrated promising anti-cancer properties, yet its role in EMT regulation within GBM remains unclear. This study aimed to systematically investigate the inhibitory effects of LK-A on TGF-β1-induced EMT and to elucidate the underlying molecular mechanisms contributing to its anti-invasive potential in GBM. LK-A inhibited EMT-associated phenotypic changes, including reduced expression of mesenchymal markers (N-cadherin, Vimentin) and increased expression of epithelial markers (ZO-1, Occludin), alongside suppression of key EMT transcription factors (Snail, Twist1). Functionally, LK-A impaired EMT-induced cell migration, invasion, and glioma stem cell-like traits, evidenced by decreased gliosphere formation and downregulation of stemness markers such as Sox2 and Oct4. Mechanistic analyses revealed that LK-A triggered reactive oxygen species (ROS) accumulation, leading to the activation of the JNK/p38 MAPK signaling cascade. Pharmacological inhibition of JNK or ROS scavenging reversed the anti-EMT effects of LK-A, confirming that EMT suppression is mediated through ROS-dependent JNK activation. In vivo, LK-A significantly suppressed tumor growth, EMT marker expression, and stemness in xenograft models. Collectively, these findings identify LK-A as a potent regulator of EMT and glioma stemness via ROS/JNK signaling. This work provides new mechanistic insight into the anti-tumor effects of LK-A and highlights its potential as a promising therapeutic strategy for combating GBM aggressiveness.

Glypican-3 (GPC3) has been identified as a compelling target for immunotherapy against hepatocellular carcinoma (HCC), owing to its selective expression on tumor cells. Chimeric antigen receptor invariant natural killer T (CAR-iNKT) cells have emerged as an innovative alternative to CAR-T cells, offering potential advantages for allogeneic applications in cellular therapy. In this study, we engineered GPC3-targeted CAR-iNKT cells and demonstrated their specific cytotoxic activity against GPC3-positive HCC cells in vitro. Using a murine HCC model, we further validated that GPC3 CAR-iNKT cells effectively suppressed tumor progression and enhanced survival outcomes. Pharmacokinetic studies showed favorable persistence of CAR-iNKT cells in vivo, with low off-target toxicity observed in critical organs. Collectively, these preclinical findings suggest that GPC3 CAR-iNKT cells may provide a safe and effective therapeutic option for HCC, warranting further investigation in clinical trials.

PTTG1 is an oncogene that is highly expressed in various cancers and is involved in regulating the cell cycle in neuroblastoma (NB) cells. However, the specific role of PTTG1 in NB has not been extensively reported. We undertook this study to investigate the expression of PTTG1 in various NB cell lines to identify the gene expression patterns.

To explore the clinical application value of modified overlap anastomosis for Siewert type II and III adenocarcinoma of esophagogastric junction, and to further evaluate its feasibility and safety.

Glioblastoma (GB) is among the most aggressive and treatment-resistant brain tumors, largely due to its heterogeneous tumor microenvironment (TME) and the protective nature of the blood-brain barrier (BBB). Recent advances have highlighted the therapeutic potential of neural stem cells (NSCs), which possess tumor-homing capabilities that enable them to selectively migrate toward and infiltrate GB sites. Engineered NSCs can deliver therapeutic agents, including oncolytic viruses, prodrug-converting enzymes, and genetic materials, offering targeted treatment while minimizing systemic toxicity. Preclinical studies have demonstrated NSCs' promise in enhancing drug delivery, modulating the TME, and promoting anti-tumor immune responses. However, translational hurdles persist, including tumor heterogeneity, species-specific immune responses, and challenges in ensuring long-term safety. Emerging strategies-such as genetic modification to improve tumor targeting and the incorporation of biomaterials to enhance retention-are under investigation. Integrating personalized medicine approaches may further optimize NSC-based therapies by tailoring treatment to individual patient profiles. While significant barriers remain, ongoing research may ultimately establish NSCs as a viable and effective platform for GB therapy.

Various immune cells infiltrate glioma tissues and secrete inflammatory mediators. This study aimed to identify inflammatory mediators in the CSF that are indicative of the tumor microenvironment (TME) and have prognostic significance in patients with glioma.

Analyze the influence of tumor vascularization and intraoperative bleeding on surgical outcomes of Grade IV Vestibular Schwannoma (VS). This single-center analytical study included patients with sporadic Grade IV VS operated on by the same surgeon in Argentina between 2011 and 2023. Clinical, imaging, surgical and pathology variables were prospectively analyzed. Tumor vascularization was assessed via preoperative perfusion MRI and correlated with intraoperative bleeding, microvascular density (CD34), and VEGF expression. Associations with facial nerve (FN) outcomes and extent of resection (EOR) were evaluated. Thirty-five adult patients (mean age 46.6; 74% male) were included. Hydrocephalus was present in 17%, and 40% had cystic tumors. High perfusion MRI values were observed in 54% (mean ratio 1.96). Arachnoid planes were clear in 49%, and 26% showed intense intraoperative bleeding. Gross-total and near-total resection were achieved in 40% and 29%, respectively. Favorable FN outcomes (House-Brackmann I-II) were seen in 52% short-term and 80% long-term. We observed a trend toward worse postoperative FN outcomes in tumors with higher intraoperative bleeding. Higher perfusion indices were associated with increased bleeding and reduced EOR. Tumor microvascular density (CD34) correlated with bleeding severity and perfusion metrics. Vascular endothelial growth factor (VEGF) expression showed a weak association with perfusion and bleeding. Preoperative perfusion imaging may help identify highly vascularized VSs prone to bleeding and poorer FN and EOR outcomes. Increased intraoperative bleeding was linked to worse postoperative FN function and limited resection. This information may assist surgeons in tailoring their strategy toward an oncofunctional resection.

Cystic renal tumors (cRT) pose technical challenges during robot-assisted partial nephrectomy (RAPN) due to the risk of cyst rupture, yet their true impact on perioperative outcomes remains unclear. This study aimed to evaluate the surgical and pathological outcomes of RAPN for cRT compared with solid renal tumors (sRT).

Metastatic pleomorphic adenoma (MPA) is a benign-appearing pleomorphic adenoma that spreads to regional and distant sites, such as lymph nodes, lungs, or bones, despite lacking malignant features histologically.

Triple-Negative Breast Cancer can develop resistance to gemcitabine and overcoming this resistance is critical for effective treatment. In cancer cells, anti-apoptotic Bcl-2 family proteins are often upregulated, disrupting apoptosis. ABT-737 binds to Bcl-2 and Bcl-xL to promote apoptosis but not Mcl-1 protein. NVP-BEZ235, a PI3K-mTOR dual inhibitor, reduces cell proliferation, increases sensitivity to chemotherapeutic agents and overcomes resistance. This study demonstrates the synergistic effects of ABT-737 and NVP-BEZ235 in overcoming gemcitabine resistance Triple-Negative Breast Cancer (MDA-MB-231GEMR) cell line. MDA-MB-231GEMR cell line was established with continuous treatment of gemcitabine and the resistance factor of MDA-MB-231GEMR cell line were confirmed via proliferation and qPCR analysis. Cytotoxicity of ABT-737, NVP-BEZ235 and combination on MDA-MB-231GEMR was assessed using Resazurin cell viability assay, resulting in a combination index value of 0.794. The effective doses were 5µM ABT-737 and 0.1µM NVP-BEZ235 for MDA-MB-231GEMR cell line at 72 h. The combination treatment reduced migration and colony formation abilities in MDA-MB-231GEMR and MDA-MB-231 cell lines. Co-treatment of both drugs induced cell cycle arrest at Sub-G0 phase in MDA-MB-231GEMR cell lines. Gene expression analysis demonstrated a significant increase in Mcl-1 expression and a reduction in Bcl-2 gene. Furthermore, hENT1 gene expression levels was also upregulated, indicating a potential reversal of resistance. Western blot analysis shows Bcl-2 protein expression levels decreased compared to control group. In silico analysis using GEPIA revealed a relation between hENT1 with Mcl-1 and Bcl2. These findings reveal ABT-737 and NVP-BEZ235 attenuate MDA-MB-231GEMR cell line and show potential implication on reversing resistance in TNBC for further studies.

Salivary gland lymphadenoma is an uncommon neoplasm and malignant transformation is even rarer. Reported tumor types include basal cell adenocarcinoma, sebaceous carcinoma, EBV-associated lymphoepithelial carcinoma, and undifferentiated carcinoma; a squamous phenotype has not been reported. Here we describe the case of a 62-year-old female who underwent total parotidectomy for a painful parotid gland mass of uncertain duration. On microscopic examination, a high grade lymphoepithelial carcinoma with squamous and poroid features arising in a non-sebaceous lymphadenoma was recognized. Both benign and malignant components expressed CK5/6 and ΔNp63 (p40), however SOX2 was overexpressed in the malignant component. S100, SOX10, CD117, PLAG1 and HMGA2 immunostains were negative. In-situ hybridization for high-risk HPV RNA and EBER were also negative. Fluorescence in situ hybridization revealed MAML2 rearrangement with RNASeq confirming a YAP1::MAML2 fusion product. This case highlights a novel salivary gland malignancy type arising from lymphadenoma, for which molecular testing was critical in establishing primary origin, and thus excluding the more common metastatic squamous cell carcinoma.

This study examined changes in muscle function over two years following diagnosis in patients with head and neck cancer (HNC), and identified demographic, lifestyle, and clinical factors associated with muscle function.

This study aimed to investigate the efficacy and safety of fruquintinib plus sintilimab in mismatch repair-proficient (pMMR)/microstatellite stable (MSS) refractory metastatic colorectal cancer (mCRC).

Nephrometry scores are essential tools for classifying and comparing tumor complexity and guiding surgical planning in partial nephrectomy. However, their performance in single-port robot-assisted partial nephrectomy (SP-RAPN) has not been formally assessed. We aimed to externally validate and compare the predictive performance of the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA), Radius-Exophytic/Endophytic-Nearness-Anterior/Posterior-Location (RENAL), and Simplified PADUA Renal (SPARE) nephrometry scores in patients undergoing SP-RAPN.

IntroductionThis study aimed to develop machine learning-based models to predict local recurrence in patients with lung oligometastases receiving stereotactic body radiotherapy (SBRT), using both clinical and radiomic features.MethodsA total of 80 lung oligometastases from 65 patients treated with SBRT were retrospectively evaluated. Clinical variables and radiomic features extracted from non-contrast planning computed tomography (CT) scans were collected. The dataset was randomly divided into training (70%) and test (30%) sets. Multivariable Cox proportional hazards models were developed to predict local recurrence using three feature sets: clinical only, radiomic only, and combined. Predictive performance was assessed using the concordance index (C-index).ResultsThe median follow-up duration was 11.8 months (range, 6.0-31.5), during which local recurrence was observed in 12 out of 80 lesions (15.0%) treated with SBRT. Multivariable Cox proportional hazards models for predicting local recurrence achieved C-index of 0.75 for the clinical model, 0.74 for the radiomic model, and 0.78 for the combined model. The combined model incorporated three features: soft tissue sarcoma histology (HR 7.70, 95% CI 1.65-35.87, p = 0.009), metastasis size (HR 1.07, 95% CI 1.01-1.14, p = 0.036), and Rad-score (HR 4.05, 95% CI 1.58-10.36, p = 0.003).ConclusionThese findings highlight the potential of machine learning-based models that integrate clinical and radiomic features to predict local recurrence in patients with lung oligometastases undergoing SBRT. Further validation in large, multicenter, and independent cohorts is needed.

Oral lichen planus (OLP) is a chronic inflammatory disorder recognised as a potentially malignant disorder of the oral cavity. This review aimed to synthesize available evidence from Saudi Arabia regarding OLP prevalence, clinical presentation, associated factors, and risk of malignant transformation.

Epithelioid fibrous histiocytoma (EFH) is a rare, benign cutaneous neoplasm, thought to be distinct from benign fibrous histiocytoma because of its characteristic anaplastic lymphoma kinase (ALK) gene rearrangements. This article presents 3 cases of EFH with unusual multinucleated giant cells, all located on acral sites. The patients, 2 women and 1 man, ranged from 24 to 63 years of age. Histopathologically, these cases exhibited well-circumscribed lesions in the dermis, composed of sheets of epithelioid cells with abundant eosinophilic cytoplasm and round nuclei within a fibrous stroma. Notably, numerous multinucleated giant cells were present, all showing ALK positivity. Clinical follow-up, ranging from 3 to 120 months, revealed no recurrence, reinforcing the benign nature of EFH. These findings highlight the importance of distinguishing EFH from other cutaneous epithelioid neoplasms with multinucleated giant cells. The presence of ALK rearrangement serves as a critical diagnostic marker. This case series expands the histopathologic spectrum of EFH and emphasizes the need for awareness of its diverse presentations to avoid misdiagnosis.

Total mesorectal excision has been adopted as standard procedure for resectable rectal cancer. However, there is no regulation in the current guidelines on the sequence of ligation of the inferior mesenteric artery and vein during rectal cancer surgery owing to a lack of sufficient evidence. Circulating tumour cells (CTCs) in peripheral blood can be used as potential indicators for predicting postoperative recurrence and prognosis in patients with colorectal cancer. The aim of the study is to investigate whether vascular ligation sequence affects the dissemination of CTCs into the bloodstream and survival during minimally invasive rectal cancer surgery.