Multimodal evaluation of 19F-BPA internalization in pancreatic cancer cells for boron capture and proton therapy potential applications.

PURPOSE: One of the obstacles to the application of Boron Neutron Capture Therapy (BNCT) and Proton Boron Fusion Therapy (PBFT) concerns the measurement of borated carriers' biodistribution. The objective of the present study was to evaluate the in vitro internalization of the 19F-labelled p-boronophenylalanine (19F-BPA) in the human cancer pancreatic cell line (PANC-1) for the potential application of BNCT and PBFT in pancreatic cancer. The 19F-BPA carrier has the advantage that its bio-distribution may be monitored in vivo using 19F-Nuclear Magnetic Resonance (19F NMR). MATERIALS AND METHODS: The 19F-BPA internalization in PANC-1 cells was evaluated using three independent techniques on cellular samples left in contact with growing medium enriched with 13.6 mM 19F-BPA corresponding to a 11B concentration of 120 ppm: neutron autoradiography, which quantifies boron; liquid chromatography hyphenated to tandem mass spectrometry and UV-Diode Array Detection (UV-DAD), which quantifies 19F-BPA molecule; and 19F NMR spectroscopy, which detects fluorine nuclei. RESULTS: Our studies suggested that 19F-BPA is internalized by PANC-1 cells. The three methods provided consistent results of about 50% internalization fraction at 120 ppm of 11B. Small variations (less than 15%) in internalization fraction are mainly dependent on the proliferation state of the cells. CONCLUSIONS: The ability of 19F NMR spectroscopy to study 19F-BPA internalization was validated by well-established independent techniques. The multimodal approach we used suggests 19F-BPA as a promising BNCT/PBFT carrier for the treatment of pancreatic cancer. Since the quantification is performed at doses useful for BNCT/PBFT, 19F NMR can be envisaged to monitor 19F-BPA bio-distribution during the therapy.

Ultrasensitive On-Field Luminescence Detection Using a Low-Cost Silicon Photomultiplier Device.

The availability of portable analytical devices for on-site monitoring and rapid detection of analytes of forensic, environmental, and clinical interest is vital. We report the development of a portable device for the detection of biochemiluminescence relying on silicon photomultiplier (SiPM) technology, called LuminoSiPM, which includes a 3D printed sample holder that can be adapted for both liquid samples and paper-based biosensing. We performed a comparison of analytical performance in terms of detectability with a benchtop luminometer, a portable cooled charge-coupled device (CCD sensor), and smartphone-integrated complementary metal oxide semiconductor (CMOS) sensors. As model systems, we used two luciferase/luciferin systems emitting at different wavelengths using purified protein solutions: the green-emitting P. pyralis mutant Ppy-GR-TS (λmax 550 nm) and the blue-emitting NanoLuc (λmax 460 nm). A limit of detection of 9 femtomoles was obtained for NanoLuc luciferase, about 2 and 3 orders of magnitude lower than that obtained with the portable CCD camera and with the smartphone, respectively. A proof-of-principle forensic application of LuminoSiPM is provided, exploiting an origami chemiluminescent paper-based sensor for acetylcholinesterase inhibitors, showing high potential for this portable low-cost device for on-site applications with adequate sensitivity for detecting low light intensities in critical fields.

Associations of meningioma molecular subgroup and tumor recurrence.

BACKGROUND: We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients. METHODS: We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan-Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling. RESULTS: Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor-associated factor 7 [TRAF7]) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence. CONCLUSION: We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.

Non-granulomatous cerebellar infection by Acanthamoeba spp. in an immunocompetent host.

Acanthamoeba spp. is a free-living amoeba, frequently involved in keratitis by contact lens in immunocompetent hosts. Anecdotal reports associate Acanthamoeba spp. as a cause of severe granulomatous encephalitis in immunocompromised and, less frequently, in immunocompetent subjects. Data regarding clinical and therapeutic management are scanty and no defined therapeutic guidelines are available. We describe an unusual case of non-granulomatous Acanthamoeba cerebellitis in an immunocompetent adult male, with abrupt onset of neurological impairment, subtle hemorrhagic infarction at magnetic resonance imaging, and initial suspicion of cerebellar neoplasm. Histopathological findings of excised cerebellar mass revealed the presence of necrosis and inflammation with structure resembling amoebic trophozoites, but without granulomas. Polymerase chain reaction from cerebellar tissue was positive for Acanthamoeba T4 genotype. Due to gastrointestinal intolerance to miltefosine, the patient was treated with long-term course of fluconazole and trimethoprim/sulphamethoxazole, obtaining complete clinical and neuroradiological resolution.

Spontaneous rupture of a secondary pituitary abscess causing acute meningoencephalitis: Case report and literature review.

BACKGROUND: Pituitary abscess (PA) is an uncommon finding that is rarely diagnosed preoperatively. If not properly treated it is associated with high morbidity and mortality rates. Nowadays standard diagnostic procedures allow early detection and successful treatment of this lesion in a high number of cases and mortality has been significantly reduced in recent years. PA arising de novo in a healthy gland are defined as primary, whereas those complicating a pre-existing disease of the hypophysis are called secondary abscesses. CASE DESCRIPTION: We present a case of a secondary PA mimicking a large pituitary adenoma extending in the nasal cavity, which was wrongly diagnosed as such. The abscess showed an unexpected evolution in 48 h from presentation due to a sudden, extensive intracranial leakage of pus. CONCLUSIONS: To our knowledge, it is rare to find PA showing a rapid evolution like this, and in the literature only one previous case of a PA not reaching medical or surgical therapy was reported. In that case, hypothalamus involvement was identified as the cause of death. This should be the first case reported of a spontaneous PA rupture causing acute meningoencephalitis. Along with a short review of the literature on the major features of PA, we also tried to identify some features which could be supportive of a diagnosis of secondary PA.