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of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

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{"project":"DLUT931","denotations":[{"id":"T2198","span":{"begin":1381,"end":1389},"obj":"Gene_expression"},{"id":"T2197","span":{"begin":823,"end":832},"obj":"Negative_regulation"},{"id":"T2196","span":{"begin":842,"end":851},"obj":"Negative_regulation"},{"id":"T2183","span":{"begin":1523,"end":1528},"obj":"Protein"},{"id":"T2182","span":{"begin":1375,"end":1380},"obj":"Protein"},{"id":"T2181","span":{"begin":836,"end":841},"obj":"Protein"},{"id":"T2180","span":{"begin":817,"end":822},"obj":"Protein"},{"id":"T2179","span":{"begin":638,"end":642},"obj":"Protein"},{"id":"T2178","span":{"begin":532,"end":537},"obj":"Protein"},{"id":"T2177","span":{"begin":518,"end":530},"obj":"Protein"},{"id":"T2176","span":{"begin":46,"end":50},"obj":"Protein"}],"relations":[{"id":"R1499","pred":"themeOf","subj":"T2180","obj":"T2197"},{"id":"R1500","pred":"themeOf","subj":"T2181","obj":"T2196"},{"id":"R1501","pred":"themeOf","subj":"T2182","obj":"T2198"},{"id":"R1508","pred":"causeOf","subj":"T2196","obj":"T2197"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"BioNLP16_Messiy","denotations":[{"id":"T2259","span":{"begin":1523,"end":1528},"obj":"Protein"},{"id":"T2258","span":{"begin":1375,"end":1380},"obj":"Protein"},{"id":"T2257","span":{"begin":836,"end":841},"obj":"Protein"},{"id":"T2256","span":{"begin":817,"end":822},"obj":"Protein"},{"id":"T2255","span":{"begin":638,"end":642},"obj":"Protein"},{"id":"T2254","span":{"begin":532,"end":537},"obj":"Protein"},{"id":"T2253","span":{"begin":518,"end":530},"obj":"Protein"},{"id":"T2252","span":{"begin":46,"end":50},"obj":"Protein"},{"id":"T2270","span":{"begin":1381,"end":1389},"obj":"Gene_expression"},{"id":"T2269","span":{"begin":823,"end":832},"obj":"Negative_regulation"},{"id":"T2268","span":{"begin":842,"end":851},"obj":"Negative_regulation"},{"id":"T2267","span":{"begin":598,"end":606},"obj":"Positive_regulation"}],"relations":[{"id":"R1528","pred":"themeOf","subj":"T2253","obj":"T2267"},{"id":"R1531","pred":"themeOf","subj":"T2256","obj":"T2269"},{"id":"R1535","pred":"themeOf","subj":"T2256","obj":"T2268"},{"id":"R1536","pred":"themeOf","subj":"T2257","obj":"T2268"},{"id":"R1539","pred":"themeOf","subj":"T2258","obj":"T2270"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"BioNLP16_DUT","denotations":[{"id":"T2138","span":{"begin":1412,"end":1421},"obj":"Gene_expression"},{"id":"T2137","span":{"begin":1381,"end":1389},"obj":"Gene_expression"},{"id":"T2136","span":{"begin":823,"end":832},"obj":"Negative_regulation"},{"id":"T2135","span":{"begin":842,"end":851},"obj":"Negative_regulation"},{"id":"T2134","span":{"begin":598,"end":606},"obj":"Positive_regulation"},{"id":"T2125","span":{"begin":1523,"end":1528},"obj":"Protein"},{"id":"T2124","span":{"begin":1375,"end":1380},"obj":"Protein"},{"id":"T2123","span":{"begin":836,"end":841},"obj":"Protein"},{"id":"T2122","span":{"begin":817,"end":822},"obj":"Protein"},{"id":"T2121","span":{"begin":638,"end":642},"obj":"Protein"},{"id":"T2120","span":{"begin":532,"end":537},"obj":"Protein"},{"id":"T2119","span":{"begin":518,"end":530},"obj":"Protein"},{"id":"T2118","span":{"begin":46,"end":50},"obj":"Protein"}],"relations":[{"id":"R1482","pred":"themeOf","subj":"T2119","obj":"T2134"},{"id":"R1483","pred":"themeOf","subj":"T2122","obj":"T2136"},{"id":"R1484","pred":"themeOf","subj":"T2122","obj":"T2135"},{"id":"R1485","pred":"themeOf","subj":"T2123","obj":"T2135"},{"id":"R1486","pred":"themeOf","subj":"T2124","obj":"T2137"},{"id":"R1487","pred":"themeOf","subj":"T2124","obj":"T2138"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

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of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"2_test","denotations":[{"id":"23459853-21406402-38778514","span":{"begin":330,"end":334},"obj":"21406402"},{"id":"23459853-21406402-38778516","span":{"begin":511,"end":515},"obj":"21406402"},{"id":"23459853-22912934-38778517","span":{"begin":696,"end":700},"obj":"22912934"},{"id":"23459853-22426504-38778518","span":{"begin":810,"end":814},"obj":"22426504"},{"id":"23459853-22532597-38778519","span":{"begin":922,"end":926},"obj":"22532597"},{"id":"23459853-22763762-38778520","span":{"begin":1111,"end":1115},"obj":"22763762"},{"id":"23459853-21988793-38778521","span":{"begin":1349,"end":1353},"obj":"21988793"},{"id":"23459853-22854781-38778522","span":{"begin":1368,"end":1372},"obj":"22854781"},{"id":"23459853-23106300-38778523","span":{"begin":1495,"end":1499},"obj":"23106300"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"GO-BP","denotations":[{"id":"T2017","span":{"begin":999,"end":1010},"obj":"http://purl.obolibrary.org/obo/GO_0032502"},{"id":"T2016","span":{"begin":408,"end":420},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T2015","span":{"begin":401,"end":420},"obj":"http://purl.obolibrary.org/obo/GO_0009435"},{"id":"T2014","span":{"begin":105,"end":114},"obj":"http://purl.obolibrary.org/obo/GO_0046960"},{"id":"T2010","span":{"begin":376,"end":396},"obj":"http://purl.obolibrary.org/obo/GO_0006284"},{"id":"T2009","span":{"begin":176,"end":196},"obj":"http://purl.obolibrary.org/obo/GO_0006284"},{"id":"T1998","span":{"begin":638,"end":642},"obj":"http://purl.obolibrary.org/obo/GO_0003908"},{"id":"T1997","span":{"begin":46,"end":50},"obj":"http://purl.obolibrary.org/obo/GO_0003908"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"GO-MF","denotations":[{"id":"T2025","span":{"begin":638,"end":642},"obj":"http://purl.obolibrary.org/obo/GO_0003908"},{"id":"T2024","span":{"begin":46,"end":50},"obj":"http://purl.obolibrary.org/obo/GO_0003908"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"GO-CC","denotations":[{"id":"T2043","span":{"begin":1564,"end":1569},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2042","span":{"begin":1464,"end":1469},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2041","span":{"begin":1442,"end":1447},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2040","span":{"begin":1402,"end":1407},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2039","span":{"begin":1130,"end":1135},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"sentences","denotations":[{"id":"T909","span":{"begin":1502,"end":1632},"obj":"Sentence"},{"id":"T908","span":{"begin":1375,"end":1501},"obj":"Sentence"},{"id":"T907","span":{"begin":1186,"end":1374},"obj":"Sentence"},{"id":"T906","span":{"begin":1118,"end":1185},"obj":"Sentence"},{"id":"T905","span":{"begin":1030,"end":1117},"obj":"Sentence"},{"id":"T904","span":{"begin":929,"end":1029},"obj":"Sentence"},{"id":"T903","span":{"begin":817,"end":928},"obj":"Sentence"},{"id":"T902","span":{"begin":703,"end":816},"obj":"Sentence"},{"id":"T901","span":{"begin":518,"end":702},"obj":"Sentence"},{"id":"T900","span":{"begin":358,"end":517},"obj":"Sentence"},{"id":"T899","span":{"begin":152,"end":357},"obj":"Sentence"},{"id":"T898","span":{"begin":0,"end":151},"obj":"Sentence"},{"id":"T34","span":{"begin":0,"end":151},"obj":"Sentence"},{"id":"T35","span":{"begin":152,"end":357},"obj":"Sentence"},{"id":"T36","span":{"begin":358,"end":517},"obj":"Sentence"},{"id":"T37","span":{"begin":518,"end":702},"obj":"Sentence"},{"id":"T38","span":{"begin":703,"end":816},"obj":"Sentence"},{"id":"T39","span":{"begin":817,"end":928},"obj":"Sentence"},{"id":"T40","span":{"begin":929,"end":1029},"obj":"Sentence"},{"id":"T41","span":{"begin":1030,"end":1117},"obj":"Sentence"},{"id":"T42","span":{"begin":1118,"end":1185},"obj":"Sentence"},{"id":"T43","span":{"begin":1186,"end":1374},"obj":"Sentence"},{"id":"T44","span":{"begin":1375,"end":1501},"obj":"Sentence"},{"id":"T45","span":{"begin":1502,"end":1632},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}

{"project":"simple1","denotations":[{"id":"T2073","span":{"begin":1523,"end":1528},"obj":"Protein"},{"id":"T2072","span":{"begin":1375,"end":1380},"obj":"Protein"},{"id":"T2071","span":{"begin":836,"end":841},"obj":"Protein"},{"id":"T2070","span":{"begin":817,"end":822},"obj":"Protein"},{"id":"T2069","span":{"begin":638,"end":642},"obj":"Protein"},{"id":"T2068","span":{"begin":532,"end":537},"obj":"Protein"},{"id":"T2067","span":{"begin":518,"end":530},"obj":"Protein"},{"id":"T2066","span":{"begin":46,"end":50},"obj":"Protein"}],"text":"Reversal of TMZ resistance may be achieved by MGMT pseudosubstrates, O6-benzylguanine and lomeguatrib to sensitize tumors to TMZ (Zhang et al., 2012b). Methoxyamine-blocker of base excision repair contributes significantly to TMZ cytotoxicity particularly when O6-methylguanine adducts are repaired or tolerated (Goellner et al., 2011; Zhang et al., 2012b). Dual targeting of base excision repair and NAD(+) biosynthesis may reverse TMZ resistance in patients with resistant and recurrent GBM (Goellner et al., 2011). Interferon-β (IFN-β), levetiracetam (LEV), resveratrol, and valproic acid (VAP) increase the sensitivity of TMZ through MGMT-dependent or -independent mechanisms (Nakada et al., 2012). Resveratrol, a natural polyphenol, reverses TMZ resistance via an NF-κB-dependent mechanism (Huang et al., 2012). STAT3 inhibitor or STAT3 knockdown potentiates TMZ efficacy in resistant GBM cell lines (Kohsaka et al., 2012). Intratumoral hypoxia is common in GBMs and may be associated with the development of TMZ resistance. Induced hyperoxia can be utilized to reverse TMZ resistance in GBMs (Sun et al., 2012). Cancer stem cells are probably the key to failure in TMZ treatment. The concept of cancer stem cell survival from treatment with TMZ and other chemotherapeutic drugs has been more complicated than previously thought (Beier et al., 2011; Chen et al., 2012). CD133-positive cancer stem cells are expressed in both normal stem cells and cancer stem cells (Donovan and Pilkington, 2012). However, the role of CD133 as a marker for glioma cancer stem cells relative to its biological function has yet to be established."}