The Experts below are selected from a list of 690468 Experts worldwide ranked by ideXlab platform
Hiroki Bukawa - One of the best experts on this subject based on the ideXlab platform.
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overexpression of stathmin in oral squamous Cell carcinoma correlation with tumour progression and poor prognosis
British Journal of Cancer, 2006Co-Authors: Yukinao Kouzu, Dai Nakashima, Yosuke Endo, Masashi Shiiba, Morihiro Higo, Hirofumi Koike, Atsushi Kasamatsu, Katsuhiro Uzawa, Kengo Saito, Hiroki BukawaAbstract:Stathmin is an intraCellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-Cell carcinoma (OSCC)-Derived Cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-Derived Cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-Derived Cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase–polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.
Yukinao Kouzu - One of the best experts on this subject based on the ideXlab platform.
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overexpression of stathmin in oral squamous Cell carcinoma correlation with tumour progression and poor prognosis
British Journal of Cancer, 2006Co-Authors: Yukinao Kouzu, Dai Nakashima, Yosuke Endo, Masashi Shiiba, Morihiro Higo, Hirofumi Koike, Atsushi Kasamatsu, Katsuhiro Uzawa, Kengo Saito, Hiroki BukawaAbstract:Stathmin is an intraCellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-Cell carcinoma (OSCC)-Derived Cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-Derived Cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-Derived Cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase–polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.
Ulrich Jage - One of the best experts on this subject based on the ideXlab platform.
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gliotoxin targets nuclear notch2 in human solid tumor Derived Cell lines in vitro and inhibits melanoma growth in xenograft mouse model
Frontiers in Pharmacology, 2017Co-Authors: Raine Hubma, Wolfgang Siegha, Susanne Schnabl, Mohammad Araghi, Marti Hilgarth, Marlies Reite, Dita Demirtas, Pete Vale, Christoph C Zielinski, Ulrich JageAbstract:Deregulation of NOTCH2 signalling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intraCellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analysed human solid tumour Derived Cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT. Electrophoretic mobility shift assays (EMSA) were used as a surrogate method for the detection of NOTCH/CSL transcription factor complexes. The effect of gliotoxin on Cell viability and its clinical relevance was evaluated in vitro and in a melanoma xenograft mouse model. Cell lines Derived from melanoma (518A2), hepatoCellular carcinoma (SNU398, HCC-3, Hep3B), and pancreas carcinoma (PANC1) express high amounts of nuclear NOTCH2. Gliotoxin efficiently induced apoptosis in these Cell lines whereas the GSI DAPT was ineffective. The specificity of gliotoxin was demonstrated in the well differentiated nuclear NOTCH negative Cell line Huh7, which was resistant to gliotoxin treatment in vitro. In xenotransplanted 518A2 melanomas, a single day dosing schedule of gliotoxin was well tolerated without any study limiting side effects. Gliotoxin significantly reduced the tumour volume in early (83mm3 vs 115mm3, p00.008) as well as in late stage (218mm3 vs 576mm3, p=0.005) tumour models. In conclusion, NOTCH2 appears to be a key target of gliotoxin in human neoplasias and gliotoxin deserves further evaluation as a potential therapeutic agent in cancer management.
Kazuhiko Yanai - One of the best experts on this subject based on the ideXlab platform.
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predominant role of plasma membrane monoamine transporters in monoamine transport in 1321n1 a human astrocytoma Derived Cell line
Journal of Neurochemistry, 2014Co-Authors: Fumito Naganuma, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Ryuichi Harada, Attayeb Mohsen, Yamato Miura, Kazuhiko YanaiAbstract:Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma-Derived Cell line. First, we confirmed that 1321N1 Cells transported dopamine, serotonin, norepinephrine, and histamine in a time- and dose-dependent manner. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 Cells was not Na+/Cl− dependent but was inhibited by decynium-22, an inhibitor of low-affinity monoamine transporters, which supported the importance of low-affinity transporters. RT-PCR assays revealed that 1321N1 Cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma-Derived Cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene-knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance. Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. We aimed to elucidate the transporters responsible for monoamine transport by astrocytes in 1321N1, a human astrocytoma-Derived Cell line. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, e.g., organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Our results indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance.
Masashi Shiiba - One of the best experts on this subject based on the ideXlab platform.
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overexpression of stathmin in oral squamous Cell carcinoma correlation with tumour progression and poor prognosis
British Journal of Cancer, 2006Co-Authors: Yukinao Kouzu, Dai Nakashima, Yosuke Endo, Masashi Shiiba, Morihiro Higo, Hirofumi Koike, Atsushi Kasamatsu, Katsuhiro Uzawa, Kengo Saito, Hiroki BukawaAbstract:Stathmin is an intraCellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-Cell carcinoma (OSCC)-Derived Cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-Derived Cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-Derived Cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase–polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.