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  1. Artikel ; Online: A Pilot Study of the Adverse Events Caused by the Combined Use of Bevacizumab and Vascular Endothelial Growth Factor Receptor-Targeted Vaccination for Patients with a Malignant Glioma

    Ryota Tamura / Yukina Morimoto / Mizuto Sato / Tetsuro Hikichi / Kazunari Yoshida / Masahiro Toda

    Vaccines, Vol 8, Iss 498, p

    2020  Band 498

    Abstract: Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF- ... ...

    Abstract Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF-A, and a multi-kinase inhibitor on VEGFRs was more effective for advanced solid cancers, including melanoma and renal cell carcinoma. However, previous clinical trials demonstrated a high adverse event rate. Additionally, no studies previously assessed treatment efficacy and safety using both VEGF-A and VEGFR-targeted agents for malignant gliomas. We had conducted clinical trials investigating VEGFRs peptide vaccination in patients with malignant gliomas, in which the treatment exhibited safety and yielded therapeutic effects in some patients. The combined use of Bev and VEGFRs vaccination may enhance the anti-tumor effect in malignant gliomas. In this pilot study, the adverse event profile in patients treated with Bev after the vaccination was investigated to establish this treatment strategy, in comparison to those treated with Bev collected from the published data or treated with the vaccination alone. In our previous clinical studies on patients with malignant gliomas, Bev was administered to 13 patients after VEGFRs vaccinations. One patient had a Grade 4 pulmonary embolism. Two patients had Grade 2 cerebral infarctions. There were no significant differences in the adverse event rates among patients treated with Bev, with the vaccination, or with Bev after the vaccination. Although careful observation is imperative for patients after this combination treatment strategy, VEGFRs-targeted vaccination may coexist with Bev for malignant gliomas.
    Schlagwörter bevacizumab ; VEGF-A ; VEGFR ; peptide vaccine ; adverse event ; malignant glioma ; Medicine ; R
    Thema/Rubrik (Code) 616 ; 610
    Sprache Englisch
    Erscheinungsdatum 2020-09-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Analysis of Tumor Angiogenesis and Immune Microenvironment in Non-Functional Pituitary Endocrine Tumors

    Mizuto Sato / Ryota Tamura / Haruka Tamura / Taro Mase / Kenzo Kosugi / Yukina Morimoto / Kazunari Yoshida / Masahiro Toda

    Journal of Clinical Medicine, Vol 8, Iss 5, p

    2019  Band 695

    Abstract: Cavernous sinus (CS) invasion is an aggressive behavior exhibited by pituitary neuroendocrine tumors (PitNETs). The cause of CS invasion in PitNETs has not been fully elucidated. The tumor immune microenvironment, known to promote aggressive behavior in ... ...

    Abstract Cavernous sinus (CS) invasion is an aggressive behavior exhibited by pituitary neuroendocrine tumors (PitNETs). The cause of CS invasion in PitNETs has not been fully elucidated. The tumor immune microenvironment, known to promote aggressive behavior in various types of tumors, has not been examined for PitNETs. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling is strongly associated with the tumor immune microenvironment. In the present study, these molecular and histopathological characteristics were examined in invasive non-functional PitNETs (NF-PitNETs). Twenty-seven patients with newly diagnosed NF-PitNETs (with CS invasion: 17, without CS invasion: 10) were analyzed by immunohistochemistry for VEGF-A/VEGFR1 and 2, hypoxia-inducible Factor (HIF), tumor-infiltrating lymphocytes, immunosuppressive cells including regulatory T cells (Tregs) and tumor-associated macrophages (TAMs), and immune checkpoint molecules. Previously validated tumor proliferation markers including mitotic count, Ki-67 index, and p53 were also analyzed for their expressions in NF-PitNETs. VEGF-A and VEGFR1 were expressed on not only vascular endothelial cells, but also on tumor cells. The expressions of VEGF-A and VEGFR1 were significantly higher in NF-PitNETs with CS invasion. The number of TAMs and the expression of PD-L1 were also significantly higher in NF-PitNETs with CS invasion than in NF-PitNETs without CS invasion. The high expression of VEGF-A and VEGFR1 and associated immunosuppressive microenvironment were observed in NF-PitNETs with CS invasion, suggesting that a novel targeted therapy can be applied.
    Schlagwörter pituitary neuroendocrine tumors ; VEGF ; Treg ; TAM ; PD-1 ; PD-L1 ; Medicine ; R
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2

    Ryota Tamura / Masato Fujioka / Yukina Morimoto / Kentaro Ohara / Kenzo Kosugi / Yumiko Oishi / Mizuto Sato / Ryo Ueda / Hirokazu Fujiwara / Shinobu Noji / Naoki Oishi / Kaoru Ogawa / Yutaka Kawakami / Takayuki Ohira / Kazunari Yoshida / Masahiro Toda

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Band 11

    Abstract: The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Here, the authors show that VEGFRs peptide vaccination can improve hearing and reduce tumor volume in NF2 ... ...

    Abstract The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Here, the authors show that VEGFRs peptide vaccination can improve hearing and reduce tumor volume in NF2 patients, including in previously bevacizumab resistant tumors.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-12-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Author Correction

    Ryota Tamura / Masato Fujioka / Yukina Morimoto / Kentaro Ohara / Kenzo Kosugi / Yumiko Oishi / Mizuto Sato / Ryo Ueda / Hirokazu Fujiwara / Tetsuro Hikichi / Shinobu Noji / Naoki Oishi / Kaoru Ogawa / Yutaka Kawakami / Takayuki Ohira / Kazunari Yoshida / Masahiro Toda

    Nature Communications, Vol 11, Iss 1, Pp 1-

    A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2

    2020  Band 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2020-04-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Author Correction

    Ryota Tamura / Masato Fujioka / Yukina Morimoto / Kentaro Ohara / Kenzo Kosugi / Yumiko Oishi / Mizuto Sato / Ryo Ueda / Hirokazu Fujiwara / Tetsuro Hikichi / Shinobu Noji / Naoki Oishi / Kaoru Ogawa / Yutaka Kawakami / Takayuki Ohira / Kazunari Yoshida / Masahiro Toda

    Nature Communications, Vol 11, Iss 1, Pp 1-

    A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2

    2020  Band 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2020-04-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2

    Ryota Tamura / Masato Fujioka / Yukina Morimoto / Kentaro Ohara / Kenzo Kosugi / Yumiko Oishi / Mizuto Sato / Ryo Ueda / Hirokazu Fujiwara / Tetsuro Hikichi / Shinobu Noji / Naoki Oishi / Kaoru Ogawa / Yutaka Kawakami / Takayuki Ohira / Kazunari Yoshida / Masahiro Toda

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Band 11

    Abstract: The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Here, the authors show that VEGFRs peptide vaccination can improve hearing and reduce tumor volume in NF2 ... ...

    Abstract The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Here, the authors show that VEGFRs peptide vaccination can improve hearing and reduce tumor volume in NF2 patients, including in previously bevacizumab resistant tumors.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2019-12-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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