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Talaporfin sodium (mono-L-aspartyl chlorin e6; NPe6), a second-generation photosensitizer, is clinically used in photodynamic therapy (PDT). It accumulates preferentially in tumors and exhibits deep tissue penetration, rapid systemic clearance, and minimal photosensitivity. However, treatment of deep-seated malignancies remains challenging. Here, we demonstrate that talaporfin sodium undergoes physicochemical reactions with X-rays to generate reactive oxygen species, a mechanism analogous to that of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX in radiodynamic therapy (RDT). To evaluate its therapeutic efficacy, we employed a pancreatic cancer xenograft model using MIA PaCa-2 cells in mice. Talaporfin sodium was administered intravenously 2 h before X-ray exposure, followed by fractionated X-ray irradiation (3 Gy daily for 3 consecutive days). Talaporfin-mediated RDT significantly inhibited tumor growth compared with radiation therapy alone. Furthermore, an exploratory RNA-seq analysis of xenografts revealed transcriptional signatures of stress and immune activation, suggesting that talaporfin-mediated RDT enhances oxidative and immunogenic responses within the tumor microenvironment. These findings highlight the potential of talaporfin sodium as a clinically translatable radiosensitizer for RDT, offering a promising strategy for the treatment of deep-seated cancers such as pancreatic carcinoma.

This study investigated the return-to-work (RTW) rates and associated factors following endoscopic transsphenoidal surgery (eTSS) among patients with pituitary and hypothalamic tumors in Japan. The primary research question aimed to determine the variables affecting early RTW post-surgery. A retrospective analysis was conducted on 44 preoperatively employed patients who underwent eTSS at a single center between April 2018 and January 2025. Clinical data, including demographics, tumor characteristics, comorbidities, and perioperative variables, were extracted from the medical records. The primary outcome was RTW within 3 months of surgery. Statistical analyses were performed using t-tests and Fisher’s exact tests. The median time to RTW was 5 weeks, and the RTW rates were 38.6%, 69.5%, and 75.0% at 1, 3, and 6 months, respectively, with an overall RTW rate of 84.1%. Factors such as a prolonged length of hospital stay (LOS), mental disorders, and the absence of prior TSS were significantly linked to delayed RTW at 3 months. Mental disorders also tended to decrease RTW at 6 months. No significant associations were found between adequate hormone replacement and age, sex, tumor type, or endocrinological dysfunction. Patients receiving multidisciplinary support for RTW tended to experience longer recovery periods, possibly reflecting a greater need. In patients undergoing eTSS for pituitary region tumors, a history of mental disorders, prolonged LOS, and no history of prior TSS were key factors could be associated with delayed RTW. Early identification of these factors may facilitate tailored multidisciplinary RTW support strategies.

Caspase-4 (CASP4) is a member of the inflammatory caspase subfamily and promotes inflammation. Here, we report that CASP4 in lung adenocarcinoma cells contributes to both tumor progression via angiogenesis and tumor hyperkinesis and tumor cell killing in response to high interferon (IFN)-γ levels. We observe that elevated CASP4 expression in the primary tumor is associated with cancer progression in patients with lung adenocarcinoma. Further, CASP4 knockout attenuates tumor angiogenesis and metastasis in subcutaneous tumor mouse models. CASP4 enhances the expression of genes associated with angiogenesis and cell migration in lung adenocarcinoma cell lines through nuclear factor kappa-light chain-enhancer of activated B cell signaling without stimulation by lipopolysaccharide or tumor necrosis factor. CASP4 is induced by endoplasmic reticulum stress or IFN-γ via signal transducer and activator of transcription 1. Most notably, lung adenocarcinoma cells with high CASP4 expression are more prone to IFN-γ-induced pyroptosis than those with low CASP4 expression. Our findings indicate that the CASP4 level in primary lung adenocarcinoma can predict metastasis and responsiveness to high-dose IFN-γ therapy due to cancer cell pyroptosis. Our findings indicate that the CASP4 level in primary lung adenocarcinoma can predict metastasis and responsiveness to high-dose IFN-γ therapy due to cancer cell pyroptosis.

Parkinsonism can be caused by a variety of factors, such as drugs, vascular disease, toxicity, infection, and autoimmune, neoplastic, metabolic and functional diseases. Parkinsonism is associated with both motor and nonmotor clinical symptoms. Notably, the accurate diagnosis of Parkinson's disease and parkinsonism remains challenging. Meningioma is the most common type of extraparenchymal brain tumor, which typically presents with headaches, focal symptoms and cranial nerve symptoms. Parkinsonism is a rare initial symptom of meningioma. The present report describes an unusual case of a 70-year-old man who presented with tremors, pill-rolling tremors and left-sided rigidity. In addition, the patient exhibited asymmetrical bradykinesia (left > right) and mild postural instability. Magnetic resonance imaging (MRI) revealed a homogeneously enhanced cerebral falx meningioma and dilated tortuous veins. Dopamine transporter single-photon emission computed tomography revealed decreased 123I-ioflupane uptake in the right striatum. The patient underwent two surgical interventions due to tumor growth and symptom deterioration. Pathological examination revealed transitional meningioma. Postoperatively, the symptoms of the patient improved, and MRI revealed a residual tumor without basal ganglia mechanical compression or venous congestion. It was hypothesized that involuntary movements, including parkinsonism in the present case, were associated with the disruption of the cortico-cerebellar-cortical and the dentato-rubro-olivary pathways (the Guillain-Mollaret triangle) due to tumor mechanical compression and venous congestion. Meningioma, which is a type of extraparenchymal tumor, is more likely to cause mechanical compression and venous congestion than the infiltration of the basal ganglia circuit, leading to symptom improvement after surgical removal. This case highlights the importance of considering meningioma as a rare cause of lateral parkinsonism and its potential for symptom improvement after surgical intervention.

Background Cleidocranial dysostosis (CCD) is an anomaly characterized by delayed closure of the cranial sutures, midface hypoplasia, moderately short stature, hypoplastic or aplastic clavicles, dental abnormalities, and other complications. Case presentation We report a case of posterior fossa subdural hematoma (PFSDH) after vaginal delivery in a neonate with CCD, which presented with several clinical symptoms such as apnea, vomiting, and bradycardia. Our patient, who had a family history of CCD, developed apnea and vomiting shortly after birth; PFSDH was detected by head computed tomography, and the patient recovered well following standard medical treatment. Conclusion The prognosis of intracranial hemorrhage in neonates with CCD is generally poor. In neonates, PFSDH occurs by the following mechanism: the distortion of the infant’s cranium during delivery, by the strong force, causes elongation of the falx and angulation of the tentorium that leads to tears in the posterior fossa venous structures, which then cause bleeding into the subdural space. In CCD, the forces occurring during vaginal delivery may causeexcessive distortion of the fragile skull. An awareness of CCD is hence important to avoid vaginal delivery in prenatally diagnosed CCD cases with a family history of CCD.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor that most commonly arises in the cerebral white matter, basal ganglia, peri-ventricle or corpus callosum. Confinement of PCNSL to the third ventricle is extremely rare, and seldom presents with intratumoral hemorrhage (ITH). The present study described the case of a 75-year-old woman who presented with obstructive hydrocephalus due to third-ventricle PCNSL. On magnetic resonance imaging (MRI), the tumor presented ITH on T2*-weighted images and a highly elevated regional cerebral blood volume on dynamic susceptibility contrast-enhanced MRI (DSC-MRI). Due to the high elevation of the regional cerebral blood volume, high-grade glioma was suspected as a preoperative diagnosis. The patient underwent endoscopic tumor biopsy and third ventricle PCNSL was successfully diagnosed. The patient achieved good prognosis at an early stage after the start of treatment initiation. There are many differential considerations for a third-ventricle tumor, and DSC-MRI can help the differential diagnosis of these tumors. Furthermore, the presence of ITH can lead to the inaccurate estimation of regional cerebral blood volume values. Overall, silent or microhemorrhage in PCNSL may be underestimated, and clinicians should therefore carefully evaluate tumor vascularity by MRI.

Glioblastoma (GBM) is the most aggressive primary malignant tumor of the adult central nervous system with poor survival outcomes despite multimodal standard treatment. Tumor-treating fields (TTFields) therapy prolongs survival in patients with newly diagnosed GBM; however, sustained adherence is essential to achieve therapeutic benefits. The risk factors for early discontinuation of TTFields remain poorly understood, as patients with treatment durations of <2-3 months have been typically excluded from previous analyses. In the present single-center retrospective study, the clinical and molecular factors associated with early discontinuation of TTFields were investigated in 16 consecutive adult patients with supratentorial GBM treated between September 2019 and February 2025. Early discontinuation was defined as the cessation of treatment within 90 days without resumption. Clinical variables, activities of daily living, neurocognitive assessments and molecular profiles were evaluated. Early discontinuation occurred in five patients (31.3%). Comparative analysis revealed that hemiparesis at treatment initiation (P=0.018), attentional impairment (P=0.036), lower baseline Karnofsky performance status (P=0.005) and Barthel Index (P=0.013) were significantly more frequent in the early discontinuation group than in the continuation group. Furthermore, overall survival was significantly shorter in the early discontinuation group (hazard ratio 8.857, 95% confidence interval 1.56-50.29, P=0.004), and progression-free survival showed a non-significant trend toward a shorter duration. No significant differences were found in the other neurocognitive test scores or molecular alterations. These findings indicated that specific neurological deficits and functional impairments may hinder treatment persistence. Therefore, early identification of at-risk patients and implementation of supportive strategies, including enhanced caregiver involvement and welfare support, may improve adherence and optimize the clinical benefits of TTFields in GBM. Key words: tumor-treating fields, glioblastoma, early discontinuation, treatment adherence, neurocognitive function, activities of daily living, molecular profiles, quality of life

Acetylcholine (ACh) acts as a neurotransmitter and neuromodulator. A small dose of eggplant powder rich in ACh (equivalent to 22 g fresh eggplant/d) has been shown to reduce blood pressure (BP) in individuals with higher BP. Here, we investigated the mechanisms underlying the antihypertensive effects of low-dose orally administered ACh in spontaneously hypertensive rats (SHRs). The effects of ACh on BP and sympathetic nervous activity (SNA), including lumbar SNA (LSNA) and renal SNA (RSNA), were evaluated by subjecting conscious SHRs to a telemetry method. Single oral administration of ACh decreased LSNA and lowered BP. Repeated oral administration of ACh for 30 d decreased RSNA and suppressed the elevated BP. Noradrenaline levels in the urine also decreased. However, vagotomy and co-administration of M3 muscarinic ACh receptor antagonist reversed the BP-lowering effect; the dynamics of non-absorbable orally administered ACh was revealed using stable isotope-labeled ACh. In conclusion, ACh acts on the gastrointestinal M3 muscarinic ACh receptor to increase afferent vagal nerve activity, which decreases SNA by autonomic reflex, suppressing noradrenaline release and lowering BP. This study suggests the use of exogenous ACh as an antihypertensive food supplement for controlling the autonomic nervous system, without absorption into the blood.