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Stryjewski, Tomasz

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Stryjewski

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Tomasz

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Stryjewski, Tomasz
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    Verteporfin inhibits growth of human glioma in vitro without light activation
    (Nature Publishing Group UK, 2017) Al-Moujahed, Ahmad; Brodowska, Katarzyna; Stryjewski, Tomasz; Efstathiou, Nikolaos; Vasilikos, Ioannis; Cichy, Joanna; Miller, Joan; Gragoudas, Evangelos; Vavvas, Demetrios
    Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.
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    Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy
    (The Association for Research in Vision and Ophthalmology, 2017) Amarnani, Dhanesh; Machuca-Parra, Arturo Israel; Wong, Lindsay L.; Marko, Christina K.; Stefater, James; Stryjewski, Tomasz; Eliott, Dean; Arboleda-Velasquez, Joseph F.; Kim, Leo
    Purpose The purpose of this study was to develop a method for isolating, culturing, and characterizing cells from patient-derived membranes in proliferative vitreoretinopathy (PVR) to be used for drug testing. Methods: PVR membranes were obtained from six patients with grade C PVR. Membrane fragments were analyzed by gross evaluation, fixed for immunohistologic studies to establish cell identity, or digested with collagenase II to obtain single cell suspensions for culture. PVR-derived primary cultures were used to examine the effects of methotrexate (MTX) on proliferation, migration, and cell death. Results: Gross analysis of PVR membranes showed presence of pigmented cells, indicative of retinal pigment epithelial cells. Immunohistochemistry identified cells expressing α-smooth muscle actin, glial fibrillary acidic protein, Bestrophin-1, and F4/80, suggesting the presence of multiple cell types in PVR. Robust PVR primary cultures (C-PVR) were successfully obtained from human membranes, and these cells retained the expression of cell identity markers in culture. C-PVR cultures formed membranes and band-like structures in culture reminiscent of the human condition. MTX significantly reduced the proliferation and band formation of C-PVR, whereas it had no significant effect on cell migration. MTX also induced regulated cell death within C-PVR as assessed by increased expression of caspase-3/7. Conclusions: PVR cells obtained from human membranes can be successfully isolated, cultured, and profiled in vitro. Using these primary cultures, we identified MTX as capable of significantly reducing growth and inducing cell death of PVR cells in vitro.
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    Severe corneal ulcer with progression to endophthalmitis and high-grade bacteremia
    (Elsevier, 2017) Stryjewski, Tomasz; Chodosh, James; Kim, Ivana; Barshak, Miriam Baron; Miller, John
    Purpose Bacterial sepsis is a common consequence of many infectious processes. Here, we describe a case of a woman with a corneal ulcer who went on to develop group B streptococcal (GBS) endophthalmitis, bacteremia, and eventual loss of the eye. Observations A previously healthy, immunocompetent, middle aged, contact lens wearing female who, after freshwater boating in her contact lenses, developed a red, painful eye. She was initially prescribed an hourly topical steroid by an outside optometrist but worsening of her condition prompted her to present to our Emergency Department. Despite aggressive initial management, the patient went on to develop GBS endophthalmitis, sepsis with high-grade bacteremia, and eventual loss of the eye. Conclusions and importance Eye care providers should exercise caution when prescribing frequent, potent corticosteroids when an infectious etiology is in the differential diagnosis.