Longitudinally extensive transverse myelitis (LETM) is a rare but severe manifestation of central nervous system (CNS) tuberculosis (TB). Because of its nonspecific clinical presentation and broad differential diagnosis, early recognition remains challenging. We report the case of a 27-year-old man with concurrent pulmonary and meningeal TB who developed rapidly progressive quadriparesis. Magnetic resonance imaging demonstrated longitudinally extensive T2-hyperintense lesions extending from C2 to T12, accompanied by diffuse meningeal enhancement, consistent with TB LETM. The patient was treated with anti-TB therapy, high-dose corticosteroids, intravenous immunoglobulin, and plasmapheresis. Despite aggressive treatment, his neurological status progressively deteriorated, ultimately resulting in death. We also conducted a comprehensive literature review to identify all previously reported cases of TB-associated LETM and summarized their clinical characteristics, extent of spinal cord involvement, treatment approaches, and outcomes. Although TB remains a major global health challenge, spinal cord involvement presenting as LETM is exceptionally rare. Prompt recognition and early initiation of appropriate therapy are essential; however, neurological outcomes may remain poor despite aggressive treatment.

Mycobacterium abscessus (MAB), a rapid growing nontuberculous mycobacterium (NTM), is an emerging pathogen mostly associated with pulmonary disease, while central nervous system (CNS) involvement remains rare and has a poor prognosis. We present a case of CNS infection caused by MAB associated with a ventriculoperitoneal (VP) shunt in an astrocytoma patient. A 21-year-old male patient, pilocytic astrocytoma with noncommunicating hydrocephalus, presented with an exposed VP shunt due to wound dehiscence. Microbiological examination of cerebrospinal fluid and shunt components, confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, identified MAB. Despite initial empirical antibiotic therapy, the patient showed no clinical improvement. Intrathecal and systemic amikacin therapy was subsequently administered, resulting in transient clinical stabilization. The infection persisted despite combined medical and surgical treatment, ultimately resulting in death. MAB CNS infection presents considerable diagnostic and therapeutic challenges due to its rarity, ambiguous clinical presentation, biofilm formation on medical devices, and intrinsic antimicrobial resistance. Management requires a combination of prolonged multidrug therapy and removal of infected device. This case highlights the importance of early recognition of NTM infections in postneurosurgical patients and underscores the need for improved therapeutic strategies for this highly resistant pathogen.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with a unique genetic and epigenetic profile and a high metastatic risk. The lack of experimental models to replicate tumor biology, including its epigenetic landscape, limits progress in translational research. Recently, patient-derived organoid (PDO) models have emerged as a promising tool for the modeling of various tumors, including UM. This study aims to establish an air-liquid interface (ALI) PDO culture system for UM, evaluate its similarity to the primary tumors, and assess its utility for drug screening.

Fresh and cryopreserved tissue samples from primary UM of 5 patients were cultured using a protocol previously validated for other malignancies. The subsequent characterization of the ALI PDOs included histologic and immunohistochemical evaluation, DNA and RNA sequencing, and histone posttranslational modification (HPTM) analysis. The model's drug-screening potential was evaluated by treating ALI PDOs with the histone deacetylase inhibitor quisinostat and comparing their responses with those of controls.

UM ALI PDOs were successfully established and retained their original tumors' immunophenotype and genetic variants. Gene expression profiling revealed similarities between PDOs and primary tumors, with main differences consisting of microenvironment-related signals. Epigenetic analysis confirmed that the overall HPTM landscape remained preserved. Treatment of the PDOs with quisinostat led to transcriptional reprogramming and the expected epigenetic response, with increased acetylation marks.

The UM ALI PDO model recapitulates the genetic and epigenetic features of primary UM and holds promise as a platform for future molecular studies and the testing of personalized therapy strategies.

Bone metastases occur in approximately two-thirds of patients with advanced cancer and are associated with pain, fractures, and neurological complications. The recently revised Dutch multidisciplinary guideline on bone metastases emphasizes early diagnosis, personalized treatment, and coordinated multidisciplinary care. We present three clinical cases highlighting key aspects of management: delayed diagnosis leading to femoral destruction and loss of mobility; a missed opportunity for prophylactic fixation in a patient with limited prognosis; and curative-intent stereotactic radiotherapy for a solitary bone metastasis. These cases illustrate the importance of timely imaging, appropriate surgical and radiotherapeutic interventions, and the use of bone-strengthening agents where indicated. Patients with bone metastases are a heterogeneous group; treatment decisions should take tumor type, extent of disease, patient condition,prognosis, and the preferences of patients into account. Implementation of the guideline requires collaboration across specialties to improve outcomes and quality of life for patients with bone metastases.

The pituitary is a rare site for metastatic spread. Pituitary metastases (PMs) account for about 1% of lesions removed by pituitary surgery. Data on epidemiology, symptoms, pituitary hormone assessment, and radiological findings are limited. This paper aimed to describe our retrospective cohort of histologically diagnosed PMs.

A single-center, retrospective, observational cohort study was conducted on patients diagnosed with PM who underwent surgical resection between 2000 to 2025. We analyzed epidemiological, clinical, radiological, and surgical data about these lesions.

Nineteen PMs were identified (9 males and 10 females). The mean age at diagnosis of PMs was 57.8 years. Most patients presented with symptoms at the first clinical evaluation, and the most frequent onset symptom was neuro-ophthalmological disorders (84.2%). Pituitary hormonal deficiencies were diagnosed in 12 patients: three patients were affected by pan-hypopituitarism (16.7%), one patient (5.5%) by anterior partial hypopituitarism, 6 patients with only an ACTH deficiency. AVD was diagnosed in 7 patients (36.8%). In 21% of patients, the pituitary gland was identified as the first site of metastasis of the primary neoplasm. Fourteen patients out of the 16 with available data (87.5%) carried residual/recurrent disease after surgery. The most frequently found neoplasms were lung cancer and breast cancer. Five patients underwent radiotherapy after surgery. Median overall survival from surgery was 23.5 months.

PMs had an increasing incidence in recent years and should be considered in the etiological diagnosis of pituitary hormonal deficiencies and/or signs due to the impairment of anatomical structures of the sella turcica.

Neuroendocrine neoplasms (NEN) are mainly located in the gastrointestinal tract or the lungs. In up to 14%, the primary tumor remains unidentified, classified as cancer of unknown primary (CUP). Due to their rarity and heterogeneity, CUPs are poorly studied.

Retrospective data analyses with data provided by the SwissNET registry from 2008-2022 including patients diagnosed with CUP or metastasised NEN with known primary (mNEN). Main objective was to assess the demographics, tumor characteristics and the diagnosis and treatment of CUPs in comparison to mNEN. Secondary objective was to evaluate overall survival of CUPs in general and compared to mNEN using propensity score matching.

207 CUP and 437 mNEN patients were included. Prevalence was slightly higher in men (54.6% and 57.9%, respectively). Median (IQR) age at diagnosis was higher for patients with a CUP (67.7 years (59.0, 77.2)) compared to mNEN (62.9 years (53.5, 71.5), p < .001). Grading in CUP patients was higher compared to mNEN with G1 (20.8% vs. 38.0%), G2 (30.4% vs. 43.5%) and G3 classified tumours ((32.9% vs. 9.6%), p < .001). Main CUP treatment involved somatostatin analogues (42%), followed by chemotherapy (32%) and PRRT (30%). Median survival time was significantly shorter for CUP patients compared to mNEN patients (23.3 months (95-CI [15.5, 31.1]) vs 151.5 months (95-CI [122.8, 180.1], p < .001)). This difference persisted after propensity score matching (p = .007).

Overall survival time of patients with CUPs was shorter compared to mNEN, possibly due to the higher-grade tumors at diagnosis.

Mucinous gastric adenocarcinoma (MGC) is a distinct histologic subtype characterized by poor prognosis and limited responsiveness to chemotherapy and immunotherapy. CRACD, an actin polymerization regulator, is frequently inactivated in gastric cancer (GC), with enrichment in mucinous subtypes. We found that genetic engineering of murine gastric organoids with Cracd ablation combined with Kras mutation and Trp53 loss induced mucinous cell plasticity, disrupted epithelial integrity, and promoted immune evasion. Mechanistically, CRACD loss triggered actin dysregulation, which activated the NF-kB/COX2 signaling and NADPH oxidase-dependent ROS generation. The resulting oxidative stress stabilized HIF1α and transactivated PD-L1, thereby disrupting anti-tumor immunity. Pharmacologic inhibition of HIF1α or PD-L1 restored immune surveillance and suppressed tumorigenesis. Clinically, analysis of patient-derived organoids and tissue microarrays demonstrated the inverse correlation between CRACD and PD-L1 expression. These findings identify CRACD inactivation as a crucial event in mucinous plasticity and immune escape in GC, further proposing that the HIF1α-PD-L1 axis is a therapeutic vulnerability in CRACD-inactivated GC.

Hypoxia-inducible factor 1 (HIF-1) orchestrates the transcriptional regulation of thousands of genes involved in breast cancer (BC) progression. Here, we identified protein phosphatase 2A (PP2A) methylesterase 1 (PPME1) as a critical HIF-1 target gene that drives oncogenic signaling under hypoxic conditions. In BC cells, HIF-1-dependent PPME1 expression caused inhibition of the PP2A catalytic subunit (PP2Ac), thereby diminishing PP2A activity, which led to AKT activation, phosphorylation of β-catenin, and its nuclear translocation. Nuclear β-catenin cooperates with HIF-1 to promote BC stem cell specification by activating transcription of the NANOG and KLF4 genes, which encode pluripotency factors, and to drive immune evasion by activating transcription of VEGFA, which recruits and polarizes immunosuppressive tumor-associated macrophages and ISG20, which represses STAT1/IRF1-dependent expression of CXCL10, thereby impairing CD8+ T cell recruitment. In vivo, PPME1 knockdown altered the tumor immune microenvironment, enhanced antitumor immunity, and synergized with anti-CTLA-4 immunotherapy to enable complete tumor eradication. These findings establish PPME1 as a critical regulator linking hypoxia signaling, stemness, and immune evasion and highlight its potential as a BC therapeutic target in combination with immune checkpoint blockade.

Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment and secrete factors that promote tumor growth, progression, and treatment resistance. Non-coding RNAs (ncRNAs) may regulate CAF-derived signals, but coordinated ncRNA-mRNA/protein networks in prostate cancer remain poorly characterized. This study aimed to identify CAF-specific ncRNA-mRNA/protein regulatory axes by comparing prostate cancer-derived CAFs with fibroblasts from benign prostatic hyperplasia (BPH).

We integrated previously generated RNA sequencing data with label-free quantitative mass spectrometry of conditioned media from primary CAFs (n=3) and BPH-derived control fibroblasts (n=3). LINCRNA-interacting miRNAs and their putative mRNA targets were predicted using NPInter v5.0 and miRDB, respectively, and cross-referenced with differentially expressed secreted proteins. Prognostic associations were evaluated using progression-free interval data from the TCGA prostate adenocarcinoma cohort.

Secretome profiling identified 1,007 proteins, including 133 differentially expressed proteins and 90 proteins unique to either CAFs or control fibroblasts. Integration of transcriptomic, target-prediction, and proteomic data revealed 28 CAF-associated ncRNA-mRNA/protein regulatory axes. MYH11, SERPINF2, ANGPT1, and CRISPLD2 were significantly associated with progression-free interval. The identified axes are linked to extracellular matrix remodeling, angiogenesis, and immune modulation, processes that contribute to tumor maintenance, progression, metastasis, and therapeutic resistance.

CAF-specific ncRNA-mRNA/protein networks provide mechanistic insight into prostate cancer progression and may serve as candidate biomarkers for disease monitoring and prognosis.

Esophageal squamous cell carcinoma (ESCC) is aggressive and has a poor prognosis. RNA-binding protein FXR1 contributes to tumor progression, but its role and mechanism in ESCC remain largely unclear. This study aimed to explore the expression, prognostic value, and molecular mechanism of FXR1 in ESCC.

FXR1 expression was detected in 115 ESCC tissues and paired normal tissues. Prognostic value was analyzed using Kaplan-Meier and Cox regression. Functional experiments were performed in ESCC cell lines and xenograft models. The mechanism was verified by RNA sequencing, RNA-binding protein immunoprecipitation, RNA pull-down, and Western blotting.

FXR1 was significantly upregulated in ESCC and correlated with distant metastasis and poor overall survival. FXR1 promoted cell migration and invasion in vitro, and knockdown suppressed tumor growth in vivo. Mechanistically, FXR1 stabilized JAK2 mRNA, activated JAK2/STAT3 signaling, and upregulated B7-H3 expression. FXR1 expression was positively associated with B7-H3 and inversely correlated with CD8⁺ T-cell infiltration.

FXR1 facilitates ESCC malignant progression and immune evasion, partially through the JAK2/STAT3/B7-H3 regulatory cascade; additional JAK2-independent pathways also contribute to B7-H3 modulation. FXR1 may act as a prognostic biomarker and promising therapeutic candidate for ESCC treatment.