Reticulocalbin-1 (RCN1), an endoplasmic reticulum (ER)-related gene, demonstrates critical regulatory functions in cellular growth. RCN1 has been previously revealed to be closely associated with initiation, metastasis and chemosensitivity in some tumors. However, the prognostic significance of RCN1 and its influence on the cancer immune microenvironment remains unclear. By leveraging multi-omics data from TCGA and GEO, this study delineated the expression profile of RCN1 across various human malignancies and normal tissues. Analysis of RCN1 expression in correlation with tumor immune microenvironment characteristics was performed using CIBERSORT and ssGSEA. Pan-cancer prognostic value was assessed via multiple survival models. In glioma, immunohistochemistry, co-culture, and qPCR were utilized to further investigate the role of RCN1 in tumor immunity and prognosis. Drug-specific responses to RCN1 expression were probed for cisplatin, irinotecan, carmustine and lomustine, which are the common chemotherapeutic agents used in glioma clinical treatment. The results indicate that RCN1 is a key gene with the potential to promote the progression of multiple tumors and is closely associated with tumor immune response, particularly macrophage activation. In glioma, overexpression of RCN1 promotes tumor proliferation and indicates poor prognosis, and is closely related to endoplasmic reticulum stress. Knockdown of RCN1 enhances the chemotherapeutic efficacy of carmustine and lomustine. In conclusion, our research positioned RCN1 as an important oncogene from a pan-cancer perspective and validated its role in glioma. In particular, RCN1 is closely associated with the immune microenvironment and endoplasmic reticulum stress during tumorigenesis. In addition, RCN1 has broad prospects in guiding tumor chemotherapy pending physiological in vivo validation.

Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is the most common subtype of autoimmune encephalitis, typically associated with ovarian teratomas, but also reported in men and children. We describe an exceptionally rare case of anti-NMDA receptor encephalitis following glioma resection. A 34-year-old man with no prior medical history presented with severe headache and generalized tonic-clonic seizure. Brain MRI suggested a tumor in the right insular region, and surgical resection confirmed a diffuse astrocytoma, WHO grade II. Postoperatively, the patient developed fever, seizures, confusion, and visual symptoms. Initial cerebrospinal fluid analysis suggested viral encephalitis, but repeated testing revealed marked pleocytosis and elevated protein. Autoimmune antibody panel confirmed anti-NMDA receptor antibody, while other antibodies and viral studies were negative. High-dose methylprednisolone and intravenous immunoglobulin therapy resulted in clinical improvement. The patient subsequently received adjuvant chemotherapy with procarbazine and lomustine for glioma, and no recurrence of encephalitis was observed during a 4-year follow-up. This case highlights the diagnostic challenge of distinguishing glioma-related neuropsychiatric symptoms from anti-NMDA receptor encephalitis, and raises the possibility that surgical manipulation may act as a trigger. Early recognition and appropriate immunotherapy remain essential for favorable outcomes. Further studies are needed to clarify the role of chemotherapy in long-term prognosis of tumor-associated anti-NMDA receptor encephalitis.

Cases of natural killer (NK)-cell large granular lymphocyte lymphoma are extremely rare, accounting for approximately 0.8% to 2.56% of lymphomas in dogs. A 5-year-old male Rottweiler presented with multiple cutaneous nodules and progressive weight loss, with a clinical course of less than 2 months. Following inconclusive cytology, an incisional biopsy was performed for histopathological and immunohistochemical analyses. Histopathological examination revealed a neoplastic proliferation of round cells infiltrating the deep dermis and subcutaneous tissue. The microscopic features, combined with the immunostaining profile-negative for CD3 and CD79a and positive for CD18 and granzyme-indicated a diagnosis of large granular lymphocyte lymphoma with a non-B/non-T immunophenotype of NK-cell origin. The patient underwent chemotherapy with lomustine and completed three treatment sessions before being euthanized, with a survival time of 93 days. Necropsy revealed involvement of the lymph nodes, heart, stomach, liver, and skin. Histopathological and immunohistochemical findings confirmed the antemortem diagnosis at all sites. To the best of our knowledge, this is the first report of cutaneous, cardiac, gastric, and hepatic involvement associated with non-B, non-T large granular lymphocyte lymphoma in dogs.

Immune checkpoint inhibitors have not demonstrated a survival benefit in unselected high-grade glioma populations; however, a subset of patients may achieve durable disease control. We report the case of a 30-year-old male patient diagnosed with a right temporoparietal high-grade glioma, initially classified as anaplastic astrocytoma and later evolving to astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 4 according to the 2021 World Health Organization classification. The patient underwent multiple surgical resections followed by radiotherapy with concomitant temozolomide and subsequent adjuvant temozolomide (Stupp protocol). Upon disease recurrence, he received second-line treatment with lomustine plus bevacizumab, with documented progression across successive lines of therapy. In the absence of standard therapeutic options, off-label nivolumab was initiated in November 2018 following further progression. The tumor harbored an IDH1 R132H mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Corticosteroids were discontinued prior to immunotherapy initiation. Serial magnetic resonance imaging demonstrated sustained radiological stability, without evidence of nodular enhancement or increased perfusion suggestive of recurrence. The most recent imaging assessment (March 2026) confirmed ongoing disease stability of more than seven years after treatment initiation. Treatment was well tolerated, with only mild immune-related arthralgias reported. The patient remains functionally independent, with stable mild residual hemiparesis. This case highlights the potential for prolonged disease stability under anti-Programmed cell death protein 1 (PD-1) therapy in selected patients with high-grade glioma. Although immunotherapy has not shown benefit in unselected populations, molecular features such as IDH mutation and MGMT promoter methylation, as well as the absence of corticosteroid use, may contribute to enhanced treatment responsiveness and warrant further investigation.

Effective chemotherapy for glioma remains limited by the restrictive nature of the blood-brain barrier (BBB). In this work, a pH-responsive polysorbate 80-coated liposomal nanocarrier loaded with lomustine (CCNU@T80-LIP) was developed to enhance the delivery and therapeutic efficacy of lomustine (CCNU) against glioma. The liposomes exhibited spherical morphology, uniform size distribution, and high encapsulation efficiency. The formulation demonstrated pH-triggered drug release under acidic conditions, supporting its potential for endosomal escape and controlled intracellular delivery. In vitro studies revealed that CCNU@T80-LIP exhibited strong, dose-dependent cytotoxicity against U87-MG glioma cells while maintaining minimal toxicity toward hCMEC/D3 endothelial cells. In 3D tumor spheroids, the formulation achieved enhanced penetration and reduced cell viability to 76.81 ± 14.29%, compared with 92.32 ± 9.79% for free CCNU. Furthermore, in a coculture BBB model in a transwell system, coumarin-6 loaded T80-LIP displayed approximately 1.5-fold higher permeability than the uncoated formulation (Cou6@LIP) and significantly decreased glioma viability (64.37 ± 3.54%) without compromising endothelial integrity. Overall, CCNU@T80-LIP demonstrates efficient BBB translocation, pH-responsive release, and potent tumor-selective cytotoxicity, highlighting its potential as an effective nanocarrier for glioma chemotherapy.

Hypertrophic osteopathy (HO) is a paraneoplastic or parainflammatory syndrome characterised by painful periosteal new bone formation and soft tissue swelling, most commonly associated with thoracic neoplasia. The pathogenesis of HO remains incompletely understood and may involve neurovascular mechanisms, altered pulmonary filtration of megakaryocytes and platelets and increased release of growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). This report describes the first documented case of HO associated with primary pulmonary histiocytic sarcoma (PHS) in a dog. A 7-year-old male Golden Retriever was referred for evaluation of diffuse pain, limb swelling and lameness. Diagnostic imaging revealed bilateral periosteal proliferation affecting the forelimbs and a pulmonary mass within the right caudal lung lobe. Histopathology and immunohistochemistry following lung lobectomy and lymphadenectomy confirmed a diagnosis of PHS with nodal metastasis. Surgical excision resulted in complete clinical resolution of pain despite persistent radiographic evidence of HO. Subsequent disease progression occurred despite multiple chemotherapy protocols, including lomustine, vinorelbine, and metronomic chemotherapy; however, the dog remained consistently pain-free throughout follow-up. Overall survival time was 450 days. This case expands the spectrum of neoplasms associated with HO and further supports the hypothesis that tumour location, rather than histotype, plays a central role in the development of this syndrome. Moreover, the sustained absence of pain despite persistent periosteal lesions and metastatic progression suggests that tumour burden and tumour microenvironment may significantly influence clinical manifestations of HO.

Predicting tablet disintegration and dissolution remains challenging due to the complex and nonlinear interplay of critical material attributes (CMAs) and physicochemical properties. This study introduces a population balance model (PBM) framework to simulate the disintegration and dissolution of tablets produced via granulation and direct compression while reducing the required experimental dataset. The framework captures the influence of CMAs, including crystal size distribution (CSD), granule size distribution (GSD), tablet and granule porosity, manufacturing routes, and active pharmaceutical ingredient (API) solubility. For granule-based tablets, an integrated system of three PBMs characterizes the number density evolution of (i) granules bound within the tablet, (ii) granules released into the solvent, and (iii) crystals. Two breakage kernels describing tablet break-up and granule fragmentation incorporate tablet porosity, granule size and porosity, and swelling-driven diffusion effects. Dissolution of crystals and granule surface erosion are modeled using a modified Noyes-Whitney equation. Experimentally determined GSD and CSD are used as initial conditions and model inputs. This framework can also be simplified into two PBMs to simulate dissolution behavior of direct compression tablets. Model accurately reproduced the dissolution behavior of acetaminophen, indomethacin, and lomustine tablets prepared via dry granulation and direct compression, with similarity factor f2 values above 50 between predicted and experimental profiles. The semi-mechanistic nature of the framework provides mechanistic insight into dissolution behavior while reducing the need for extensive dissolution data, which may facilitate and accelerate tablet formulation development.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains a key consolidation strategy for patients with relapsed/refractory (R/R) lymphoma. The BEAM regimen (carmustine, etoposide, cytarabine, melphalan) is the standard conditioning therapy, but clinical carmustine supply shortages have necessitated the search for alternatives. This study compared the toxicity and transplant outcomes of four carmustine-substituted conditioning regimens. We retrospectively analyzed 80 lymphoma patients who underwent ASCT between January 2018 and December 2023. Patients received one of four regimens: BeEAM (bendamustine, etoposide, cytarabine, melphalan; n = 16), CBV (cyclophosphamide, oral semustine, etoposide; n = 12), CEAC (oral semustine, etoposide, cytarabine, cyclophosphamide; n = 16), or SEAM (oral semustine, etoposide, cytarabine, melphalan; n = 36). The primary endpoint was severe toxicity. Secondary endpoints included progression-free survival (PFS), overall survival (OS), complete response rate (CRR) and non-relapse mortality. The SEAM regimen was associated with a significantly higher rate of BNP elevation (61.1%, p = 0.040). All patients in the BeEAM group developed febrile neutropenia (p = 0.004), and this regimen also led to more platelet transfusions (median 6.5 units, p = 0.001) and longer hospital stays (median 28.5 days, p = 0.012). The CBV group had the highest rate of cardiovascular adverse events (25.0%, p = 0.081), while the CEAC group showed the highest incidence of hypoproteinemia (100.0%, p = 0.006) and a notably high rate of intestinal infection (81.3%, p = 0.069). No significant intergroup differences were observed in PFS, OS, day + 100 CRR, or non-relapse mortality. Multivariate Cox analysis identified pre-transplant partial remission as an independent adverse prognostic factor for PFS (HR: 4.864; 95% CI: 1.094-21.634, p = 0.038). Although the four carmustine-substituted conditioning regimens demonstrated similar efficacy outcomes for ASCT in lymphoma patients, their distinct toxicity profiles highlight the need for personalized regimen selection, particularly in the context of carmustine shortages.

Tumor treating fields (TTFields) therapy at 200 kHz is FDA-approved for supratentorial glioblastoma. However, reports of TTFields in patients with infratentorial high-grade glioma (HGG) are rare. Two patients with infratentorial HGG received off-label 200 kHz TTFields. To reduce impaired neck range of motion, the electrode transducer arrays were "skeletonized" by cutting a portion of the adhesive material. The electrode arrays were applied with the neck in flexion to further promote range of neck motion. Patient 1, a 22-year-old man with high-grade diffuse pontine glioma with recurrences and prior treatments, tolerated TTFields combined with systemic treatment (initially with a bifunctional DNA alkylating agent; subsequently with temozolomide and bevacizumab) for 5 months with stable disease for 4 months. He experienced grade 1 rash (neck). Patient 2, a 58-year-old woman with diffuse glioma of the brainstem (H3K27M-mutated) with multiple recurrences and prior treatments, tolerated TTFields combined with systemic treatment (lomustine and bevacizumab). With the TTFields + systemic combination therapy, the patient was stable for 8 months with no TTFields-related side effects. We provide two initial post-marketing cases demonstrating that off-label use of 200 kHz TTFields in infratentorial HGG is safe and feasible. Prospective studies are necessary to validate the efficacy of this approach.