JaLCDOI 10.18926/AMO/53999
FullText URL 70_1_13.pdf
Author Arum Tri Wahyuningsih| Shen, Lianhua| Kobayashi, Kazuko| Sasaki, Takanori| Takenaka, Fumiaki| Hanada, Takahisa| Akehi, Masaru| Akahoshi, Akiya| Ozeki, Eiichi| Ando, Eiji| Matsuura, Eiji|
Abstract Intact β2-glycoprotein I (iβ2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked β2GPI (nβ2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of βi 2GPI and nβ2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected β2GPI variants in tumor lesions in mice. iβ2GPI was incubated with plasmin to obtain nβ2GPI, and its N-terminal sequence was analyzed. nβ2GPI had at least one other cleavage site upstream of the β2GPIʼs domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked β2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested β2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that β2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis.
Keywords β2-glycoprotein I (β2GPI) angiogenesis vascular endothelial growth factor-A (VEGF-A) positron emission tomography (PET) imaging
Amo Type Original Article
Published Date 2016-02
Publication Title Acta Medica Okayama
Volume volume70
Issue issue1
Publisher Okayama University Medical School
Start Page 13
End Page 24
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2016 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 26899605
Web of Sience KeyUT 000371288700002
JaLCDOI 10.18926/AMO/52009
FullText URL 67_6_359.pdf
Author Katashima, Kazunori| Kuroda, Masahiro| Ashida, Masakazu| Sasaki, Takanori| Taguchi, Takehito| Matsuzaki, Hidenobu| Murakami, Jun| Yanagi, Yoshinobu| Hisatomi, Miki| Hara, Marina| Kato, Hirokazu| Ohmura, Yuichi| Kobayashi, Tomoki| Kanazawa, Susumu| Harada, Sosuke| Takemoto, Mitsuhiro| Ohno, Seiichiro| Mimura, Seiichi| Asaumi, Junichi|
Abstract It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3μm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis.
Keywords ADC apoptosis necrosis hyperthermia cell density
Amo Type Original Article
Published Date 2013-12
Publication Title Acta Medica Okayama
Volume volume67
Issue issue6
Publisher Okayama University Medical School
Start Page 359
End Page 367
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2013 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 24356720
Web of Sience KeyUT 000328915700004
JaLCDOI 10.18926/AMO/48566
FullText URL 66_3_263.pdf
Author Sasaki, Takanori| Kuroda, Masahiro| Katashima, Kazunori| Ashida, Masakazu| Matsuzaki, Hidenobu| Asaumi, Junichi| Murakami, Jun| Ohno, Seiichiro| Kato, Hirokazu| Kanazawa, Susumu|
Abstract The roles of cell density, extracellular space, intracellular factors, and apoptosis induced by the molecularly targeted drug rituximab on the apparent diffusion coefficient (ADC) values were investigated using bio-phantoms. In these bio-phantoms, Ramos cells (a human Burkittセs lymphoma cell line) were encapsulated in gellan gum. The ADC values decreased linearly with the increase in cell density, and declined steeply when the extracellular space became less than 4 μm. The analysis of ADC values after destruction of the cellular membrane by sonication indicated that approximately 65% of the ADC values of normal cells originate from the cell structures made of membranes and that the remaining 35% originate from intracellular components. Microparticles, defined as particles smaller than the normal cells, increased in number after rituximab treatments, migrated to the extracellular space and significantly decreased the ADC values of bio-phantoms during apoptosis. An in vitro study using bio-phantoms was conducted to quantitatively clarify the roles of cellular factors and of extracellular space in determining the ADC values yielded by tumor cells and the mechanism by which apoptosis changes those values.
Keywords apparent diffusion coefficient value cell density extracellular space bio-phantom
Amo Type Original Article
Published Date 2012-06
Publication Title Acta Medica Okayama
Volume volume66
Issue issue3
Publisher Okayama University Medical School
Start Page 263
End Page 270
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2012 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 22729107
Web of Sience KeyUT 000305669700010