Porciuncula, A. (Angelo)

Filtering

2013 - 20192

Settings

Author search.filters.isAuthorOfPublication.9e9d9be8-f020-4396-86a1-a47ef404cafb

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma
    (Nature Publishing Group, 2019) Berraondo, P. (Pedro); Perez-Gracia, J.L. (Jose Luis); Rodriguez-Ruiz, M.E. (María Esperanza); Lopez-Diaz-de-Cerio, A. (Ascensión); Tejada-Solis, S. (Sonia); Diez-Valle, R. (Ricardo); Goicoechea, I. (Iosune); Inoges, S. (Susana); Gurpide, A. (Alfonso); Melero, I. (Ignacio); Choi, J. (Jungmin); Porciuncula, A. (Angelo); Idoate, M.A. (Miguel Ángel); Andrea, C.E. (Carlos Eduardo) de; López-Janeiro, Á. (Álvaro); Gallego-Perez-Larraya, J. (Jaime); Villarroel-Espindola, F. (Franz); Schalper, K.A. (Kurt A.); Giraldez, M. (Miriam); Fernandez-Sanmamed, M. (Miguel)
    Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3 cases of primary surgery for newly diagnosed patients). Availability of tumor tissue pre- and post-nivolumab dosing and from additional patients who did not receive nivolumab allowed the evaluation of changes in the tumor immune microenvironment using multiple molecular and cellular analyses. Neoadjuvant nivolumab resulted in enhanced expression of chemokine transcripts, higher immune cell infiltration and augmented TCR clonal diversity among tumor-infiltrating T lymphocytes, supporting a local immunomodulatory effect of treatment. Although no obvious clinical benefit was substantiated following salvage surgery, two of the three patients treated with nivolumab before and after primary surgery remain alive 33 and 28 months later.
  • Thumbnail Image
    Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells
    (Public Library of Science, 2013) Esguerra, C. (Camila); Hering, B. (Bernhard); Lo-Nigro, A. (Antonio); Heremans, Y. (Y.); Kumar, A. (Anujith); Mathieu, C. (Chantal); Cai, Q. (Qing); Barajas, M. (Miguel); Porciuncula, A. (Angelo); Nelson-Holte, M. (Molly); Gysemans, C. (Conny); Heimberg, H. (Harry); Prosper-Cardoso, F. (Felipe); Jimenez-Gonzalez, M. (María); Verfaillie, C.M. (Catherine M.); Binas, B. (Bert)
    β-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting β-cells have been selectively destroyed by autoantigen-reactive T cells. To generate insulin-secreting cells we used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly similar rat extra-embryonic endoderm precursor (rXEN-P) cells isolated under rMAPC conditions from blastocysts (rHypoSC). rMAPC/rHypoSC were sequentially committed to definitive endoderm, pancreatic endoderm, and β-cell like cells. On day 21, 20% of rMAPC/rHypoSC progeny expressed Pdx1 and C-peptide. rMAPCr/HypoSC progeny secreted C-peptide under the stimulus of insulin agonist carbachol, and was inhibited by the L-type voltage-dependent calcium channel blocker nifedipine. When rMAPC or rHypoSC differentiated d21 progeny were grafted under the kidney capsule of streptozotocin-induced diabetic nude mice, hyperglycemia reversed after 4 weeks in 6/10 rMAPC- and 5/10 rHypoSC-transplanted mice. Hyperglycemia recurred within 24 hours of graft removal and the histological analysis of the retrieved grafts revealed presence of Pdx1-, Nkx6.1- and C-peptide-positive cells. The ability of both rMAPC and HypoSC to differentiate to functional β-cell like cells may serve to gain insight into signals that govern β-cell differentiation and aid in developing culture systems to commit other (pluripotent) stem cells to clinically useful β-cells for cell therapy of T1D.