Kinetics of porphyrin fluorescence accumulation in pediatric brain tumor cells incubated in 5-aminolevulinic acid.

BACKGROUND: Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) enables more complete resections of tumors in adults. 5-ALA elicits accumulation of fluorescent porphyrins in various cancerous tissues, which can be visualized using a modified neurosurgical microscope with blue light. Although this technique is well established in adults, it has not been investigated systematically in pediatric brain tumors. Specifically, it is unknown how quickly, how long, and to what extent various pediatric tumors accumulate fluorescence. The purpose of this study was to determine utility and time course of 5-ALA-induced fluorescence in typical pediatric brain tumors in vitro. METHODS: Cell cultures of medulloblastoma [DAOY and UW228], cPNET [PFSK] atypical teratoid rhabdoid tumor [BT16] and ependymoma [RES196] were incubated with 5-ALA for either 60 minutes or continuously. Porphyrin fluorescence intensities were determined using a fluorescence-activated cell sorter (FACS) after 1, 3, 6, 9, 12 and 24 hours. C6 and U87 cells served as controls. RESULTS: All pediatric brain tumor cell lines displayed fluorescence compared to their respective controls without 5-ALA (p < 0.05). Sixty minutes of incubation resulted in peaks between 3 and 6 hours, whereas continuous incubation resulted in peaks at 12 hours or beyond. 60 minute incubation peak levels were between 52 and 91 % of maxima achieved with continuous incubation. Accumulation and clearance varied between cell types. CONCLUSIONS: We demonstrate that 5-ALA exposure of cell lines derived from typical pediatric central nervous system (CNS) tumors induces accumulation of fluorescent porphyrins. Differences in uptake and clearance indicate that different application modes may be necessary for fluorescence-guided resection, depending on tumor type.

Analysis of the Spinopelvic Parameters in Patients with Fragility Fractures of the Pelvis.

BACKGROUND: We investigated the spinopelvic parameters of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) in patients with fragility fractures of the pelvis (FFPs). We hypothesized that these parameters differ from asymptomatic patients. METHODS: All patients treated for FFPs in a center of maximal care of the German Spine Society (DWG) between 2017 and 2021 were included. The inclusion criteria were age ≥ 60 years and the availability of a standing lateral radiograph of the spine and pelvis in which the spine from T12 to S1 and both femoral heads were visible. The baseline characteristics and study parameters were calculated and compared with databases of asymptomatic patients. The two-sample t-Test was performed with p < 0.05. RESULTS: The study population (n = 57) consisted of 49 female patients. The mean age was 81.0 years. The mean LL was 47.9°, the mean PT was 29.4°, the mean SS was 34.2° and the mean PI was 64.4°. The mean value of LLI was 0.7. LL, LLI and SS were significantly reduced, and PI and PT were significantly increased compared to asymptomatic patients. CONCLUSIONS: The spinopelvic parameters in patients with FFPs differ significantly from asymptomatic patients. In patients with FFPs, LL, LLI and SS are significantly reduced, and PI and PT are significantly increased. The sagittal spinopelvic balance is abnormal in patients with FFPs.

Co-application of arsenic trioxide (As2O3) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca2+]i) and cytotoxicity.

Arsenic trioxide (As(2)O(3)) and cisplatin (CDDP) are clinically relevant chemotherapeutics which modulate the intracellular calcium concentration ([Ca(2+)](i)) by different mechanisms: As(2)O(3) depletes intracellular calcium stores while CDDP triggers an influx of Ca(2+). We investigate whether co-application of As(2)O(3) and CDDP has an effect on [Ca(2+)](i) homeostasis, resulting in an increase of cytotoxicity/apoptosis in human SY-5Y neuroblastoma cells. Confocal imaging with Ca(2+)-sensitive dye (fluo-4) was used for investigating [Ca(2+)](i) dynamics. The induction of cell death was assayed using Trypan blue exclusion and Hoechst 33347 staining. Application of As(2)O(3) (1microM) or CDDP (1microM) increased [Ca(2+)](i). The largest elevation was observed when the basic [Ca(2+)](i) concentration was low. Both, transient and sustained [Ca(2+)](i)-increases were observed in response to a single application of As(2)O(3) or CDDP. Sustained increase showed clear additive effects when both drugs were co-applied. The magnitude of the [Ca(2+)](i)-increase depends on the order of application; the most pronounced effect occurred when the cells were preincubated with CDDP followed by a co-application with As(2)O(3). The sustained [Ca(2+)](i) elevations resulted in increased cytotoxicity and apoptosis. Therefore, co-treatment with CDDP and As(2)O(3) may be a more effective anti-cancer therapy then either agent alone.