Christmas balls 3D Model available on Turbo Squid, the world's leading provider of digital 3D models for visualization, films, television, and games. Feb 27, 2013 - PDT Dose Parameters Impact Tumoricidal Durability and Cell Death Pathways in a 3D Ovarian Cancer Model. Wellman Center for.

Metastatic ovarian cancer (OvCa) frequently recurs due to chemoresistance, highlighting the need for nonoverlapping combination therapies that mechanistically synergize to eradicate residual disease. Photodynamic therapy (PDT), a photochemistry-based cytotoxic modality, sensitizes ovarian tumors to platinum agents and biologics and has shown clinical promise against ovarian carcinomatosis. We introduce a three-dimensional (3D) model representing adherent ovarian micrometastases and high-throughput quantitative imaging methods to rapidly screen the order-dependent effects of combining benzoporphyrin-derivative (BPD) monoacid A-based PDT with low-dose carboplatin. 3D ovarian micronodules grown on Matrigel were subjected to BPD-PDT either before or after carboplatin treatment. We developed custom fluorescence image analysis routines to quantify residual tumor volume and viability. Carboplatin alone did not eradicate ovarian micrometastases at a dose of 400 mg/m2, leaving surviving cores that were nonsensitive or impermeable to chemotherapy.

BPD-PDT (1.25 μmol/LJ/cm2) created punctate cytotoxic regions within tumors and disrupted micronodular structure. Treatment with BPD-PDT prior to low-dose carboplatin (40 mg/m2) produced a significant synergistic reduction [P. Biological characterization of a 3D model for micrometastatic OvCa. A, OVCAR5 cells overlaid on GFR-Matrigel™ formed 3D ovarian micronodules representing adherent micrometastatic disease with B, punctate E-cadherin expression, and C, fibronectin (red) expression (blue: DAPI), markers for poor prognosis. D, mean diameter increased from 34.3μm (±2.6μm) 3 days post-plating ( n = 9) to 108.9μm (± 13.0μm) at day 10 ( n = 9) and 131.9μm (±25.3μm) at day 17 ( n = 3) (E). Scale bars: (B) and (C), 20μm; (D) 150μm. Monolayer cultures significantly overestimate carboplatin and BPD-PDT efficacy compared to cells in 3D.

A, fractional viability of OVCAR5 cells in monolayer (striped) following carboplatin treatment (40 mg/m 2) was 0.30 (± 0.082) ( n = 10), as compared to 0.90 (± 0.057) in 3D (solid), ( n = 6) ( p. Differential patterns of cytotoxic response in carboplatin and BPD-PDT treated 3D micronodules.

Facsdiva manual. A, left, a representative micronodule treated with 400 mg/m 2 carboplatin showing cell death (ethidium bromide) on the periphery of a viable (calcein) tumor core, with A, right, distinct and minimally overlapping fluorescence intensity profiles. B, left, BPD-PDT 1.25μMJ/cm 2 treatment leads to nodular disruption and punctate cytoxicity. B, right, intensity profile scans through two regions of interest (yellow boxes) show highly overlapping fluorescence patterns. Scale bars = 25μm. BPD-PDT synergizes with low-dose carboplatin to reduce residual tumor volume. A, images of residual disease (calcein).

B, fraction residual tumor following carboplatin alone or BPD-PDT alone was 0.95 (95% CI=0.83-1.09, n = 11) and 0.76 (95% CI=0.63-0.92 n = 15), respectively, relative to no treatment (grey dashed line). The combination treatment, BPD-PDT followed by carboplatin, produced a synergistic reduction in residual tumor to 0.26 (95% CI=0.19-0.36, n = 11) ( p. BPD-PDT followed by carboplatin synergistically reduces tumor viability. A, images of tumor viability (calcein and ethidium bromide fluorescence) following treatment. B, mean fraction viability in micronodules treated with either carboplatin alone or BPD-PDT alone was 0.92 (95% CI=0.88-0.97, n = 11) and 0.80 (95%CI=0.74-0.86, n = 15), respectively, relative to no treatment (grey dashed line). The combination treatment, BPD-PDT followed by carboplatin, reduced viability to 0.45 (95% CI=0.38-0.53, n = 11), indicating a significant synergism ( p.