PubMed:20630060 JSON TXT

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PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":186,"end":199},"obj":"HP_0003002"},{"id":"T2","span":{"begin":186,"end":199},"obj":"HP_0100013"},{"id":"T3","span":{"begin":193,"end":199},"obj":"HP_0002664"},{"id":"T4","span":{"begin":346,"end":359},"obj":"HP_0003002"},{"id":"T5","span":{"begin":346,"end":359},"obj":"HP_0100013"},{"id":"T6","span":{"begin":353,"end":359},"obj":"HP_0002664"},{"id":"T7","span":{"begin":514,"end":527},"obj":"HP_0003002"},{"id":"T8","span":{"begin":514,"end":527},"obj":"HP_0100013"},{"id":"T9","span":{"begin":521,"end":527},"obj":"HP_0002664"},{"id":"T10","span":{"begin":555,"end":569},"obj":"HP_0003002"},{"id":"T11","span":{"begin":555,"end":569},"obj":"HP_0100013"},{"id":"T12","span":{"begin":562,"end":569},"obj":"HP_0002664"},{"id":"T13","span":{"begin":833,"end":847},"obj":"HP_0100615"},{"id":"T14","span":{"begin":841,"end":847},"obj":"HP_0002664"},{"id":"T15","span":{"begin":1072,"end":1085},"obj":"HP_0001427"},{"id":"T16","span":{"begin":1260,"end":1273},"obj":"HP_0003002"},{"id":"T17","span":{"begin":1260,"end":1273},"obj":"HP_0100013"},{"id":"T18","span":{"begin":1267,"end":1273},"obj":"HP_0002664"}],"text":"Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo.\nINTRODUCTION: Triple-negative breast cancer does not express estrogen and progesterone receptors, and no overexpression/amplification of the HER2-neu gene occurs. Therefore, this subtype of breast cancer lacks the benefits of specific therapies that target these receptors. Today chemotherapy is the only systematic therapy for patients with triple-negative breast cancer. About 50% to 64% of human breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a target. New targeted therapies are warranted. Recently, we showed that antagonists of gonadotropin-releasing hormone type II (GnRH-II) induce apoptosis in human endometrial and ovarian cancer cells in vitro and in vivo. This was mediated through activation of stress-induced mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK), followed by activation of proapoptotic protein Bax, loss of mitochondrial membrane potential, and activation of caspase-3. In the present study, we analyzed whether GnRH-II antagonists induce apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells that express GnRH receptors. In addition, we ascertained whether knockdown of GnRH-I receptor expression affects GnRH-II antagonist-induced apoptosis and apoptotic signaling.\nMETHODS: Induction of apoptosis was analyzed by measurement of the loss of mitochondrial membrane potential. Apoptotic signaling was measured with quantification of activated MAPK p38 and caspase-3 by using the Western blot technique. GnRH-I receptor protein expression was inhibited by using the antisense knockdown technique. In vivo experiments were performed by using nude mice bearing xenografted human breast tumors.\nRESULTS: We showed that treatment of MCF-7 and triple-negative MDA-MB-231 human breast cancer cells with a GnRH-II antagonist results in apoptotic cell death in vitro via activation of stress-activated MAPK p38 and loss of mitochondrial membrane potential. In addition, we showed GnRH-II antagonist-induced activation of caspase-3 in MDA-MB-231 human breast cancer cells. After knockdown of GnRH-I receptor expression, GnRH-II antagonist-induced apoptosis and apoptotic signaling was only slightly reduced, indicating that an additional pathway mediating the effects of GnRH-II antagonists may exist. The GnRH-I receptor seems not to be the only target of GnRH-II antagonists. The antitumor effects of the GnRH-II antagonist could be confirmed in nude mice. The GnRH-II antagonist inhibited the growth of xenotransplants of human breast cancers in nude mice completely, without any apparent side effects.\nCONCLUSIONS: GnRH-II antagonists seem to be suitable drugs for an efficacious and less-toxic endocrine therapy for breast cancers, including triple-negative breast cancers."}

Allie

{"project":"Allie","denotations":[{"id":"SS1_20630060_5_0","span":{"begin":592,"end":622},"obj":"expanded"},{"id":"SS2_20630060_5_0","span":{"begin":624,"end":628},"obj":"abbr"},{"id":"SS1_20630060_7_0","span":{"begin":742,"end":780},"obj":"expanded"},{"id":"SS2_20630060_7_0","span":{"begin":782,"end":789},"obj":"abbr"},{"id":"SS1_20630060_8_0","span":{"begin":931,"end":964},"obj":"expanded"},{"id":"SS2_20630060_8_0","span":{"begin":966,"end":971},"obj":"abbr"},{"id":"SS1_20630060_8_1","span":{"begin":981,"end":1004},"obj":"expanded"},{"id":"SS2_20630060_8_1","span":{"begin":1006,"end":1009},"obj":"abbr"}],"relations":[{"id":"AE1_20630060_5_0","pred":"abbreviatedTo","subj":"SS1_20630060_5_0","obj":"SS2_20630060_5_0"},{"id":"AE1_20630060_7_0","pred":"abbreviatedTo","subj":"SS1_20630060_7_0","obj":"SS2_20630060_7_0"},{"id":"AE1_20630060_8_0","pred":"abbreviatedTo","subj":"SS1_20630060_8_0","obj":"SS2_20630060_8_0"},{"id":"AE1_20630060_8_1","pred":"abbreviatedTo","subj":"SS1_20630060_8_1","obj":"SS2_20630060_8_1"}],"text":"Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo.\nINTRODUCTION: Triple-negative breast cancer does not express estrogen and progesterone receptors, and no overexpression/amplification of the HER2-neu gene occurs. Therefore, this subtype of breast cancer lacks the benefits of specific therapies that target these receptors. Today chemotherapy is the only systematic therapy for patients with triple-negative breast cancer. About 50% to 64% of human breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a target. New targeted therapies are warranted. Recently, we showed that antagonists of gonadotropin-releasing hormone type II (GnRH-II) induce apoptosis in human endometrial and ovarian cancer cells in vitro and in vivo. This was mediated through activation of stress-induced mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK), followed by activation of proapoptotic protein Bax, loss of mitochondrial membrane potential, and activation of caspase-3. In the present study, we analyzed whether GnRH-II antagonists induce apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells that express GnRH receptors. In addition, we ascertained whether knockdown of GnRH-I receptor expression affects GnRH-II antagonist-induced apoptosis and apoptotic signaling.\nMETHODS: Induction of apoptosis was analyzed by measurement of the loss of mitochondrial membrane potential. Apoptotic signaling was measured with quantification of activated MAPK p38 and caspase-3 by using the Western blot technique. GnRH-I receptor protein expression was inhibited by using the antisense knockdown technique. In vivo experiments were performed by using nude mice bearing xenografted human breast tumors.\nRESULTS: We showed that treatment of MCF-7 and triple-negative MDA-MB-231 human breast cancer cells with a GnRH-II antagonist results in apoptotic cell death in vitro via activation of stress-activated MAPK p38 and loss of mitochondrial membrane potential. In addition, we showed GnRH-II antagonist-induced activation of caspase-3 in MDA-MB-231 human breast cancer cells. After knockdown of GnRH-I receptor expression, GnRH-II antagonist-induced apoptosis and apoptotic signaling was only slightly reduced, indicating that an additional pathway mediating the effects of GnRH-II antagonists may exist. The GnRH-I receptor seems not to be the only target of GnRH-II antagonists. The antitumor effects of the GnRH-II antagonist could be confirmed in nude mice. The GnRH-II antagonist inhibited the growth of xenotransplants of human breast cancers in nude mice completely, without any apparent side effects.\nCONCLUSIONS: GnRH-II antagonists seem to be suitable drugs for an efficacious and less-toxic endocrine therapy for breast cancers, including triple-negative breast cancers."}

DisGeNET5_gene_disease

CoMAGC

{"project":"CoMAGC","denotations":[{"id":"T1","span":{"begin":2199,"end":2208},"obj":"Gene"},{"id":"E2","span":{"begin":2185,"end":2195},"obj":"Positive_regulation"},{"id":"T2","span":{"begin":2229,"end":2242},"obj":"breast cancer"},{"id":"T3","span":{"begin":2212,"end":2222},"obj":"breast cancer"}],"relations":[{"id":"R1","pred":"themeOf","subj":"T1","obj":"E2"},{"id":"R3","pred":"CGE-increased","subj":"T1","obj":"T2"},{"id":"R4","pred":"CCS-unidentifiable","subj":"T1","obj":"T2"},{"id":"R5","pred":"PT-","subj":"T1","obj":"T2"},{"id":"R3","pred":"IGE-","subj":"T1","obj":"T2"}],"text":"Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo.\nINTRODUCTION: Triple-negative breast cancer does not express estrogen and progesterone receptors, and no overexpression/amplification of the HER2-neu gene occurs. Therefore, this subtype of breast cancer lacks the benefits of specific therapies that target these receptors. Today chemotherapy is the only systematic therapy for patients with triple-negative breast cancer. About 50% to 64% of human breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a target. New targeted therapies are warranted. Recently, we showed that antagonists of gonadotropin-releasing hormone type II (GnRH-II) induce apoptosis in human endometrial and ovarian cancer cells in vitro and in vivo. This was mediated through activation of stress-induced mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK), followed by activation of proapoptotic protein Bax, loss of mitochondrial membrane potential, and activation of caspase-3. In the present study, we analyzed whether GnRH-II antagonists induce apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells that express GnRH receptors. In addition, we ascertained whether knockdown of GnRH-I receptor expression affects GnRH-II antagonist-induced apoptosis and apoptotic signaling.\nMETHODS: Induction of apoptosis was analyzed by measurement of the loss of mitochondrial membrane potential. Apoptotic signaling was measured with quantification of activated MAPK p38 and caspase-3 by using the Western blot technique. GnRH-I receptor protein expression was inhibited by using the antisense knockdown technique. In vivo experiments were performed by using nude mice bearing xenografted human breast tumors.\nRESULTS: We showed that treatment of MCF-7 and triple-negative MDA-MB-231 human breast cancer cells with a GnRH-II antagonist results in apoptotic cell death in vitro via activation of stress-activated MAPK p38 and loss of mitochondrial membrane potential. In addition, we showed GnRH-II antagonist-induced activation of caspase-3 in MDA-MB-231 human breast cancer cells. After knockdown of GnRH-I receptor expression, GnRH-II antagonist-induced apoptosis and apoptotic signaling was only slightly reduced, indicating that an additional pathway mediating the effects of GnRH-II antagonists may exist. The GnRH-I receptor seems not to be the only target of GnRH-II antagonists. The antitumor effects of the GnRH-II antagonist could be confirmed in nude mice. The GnRH-II antagonist inhibited the growth of xenotransplants of human breast cancers in nude mice completely, without any apparent side effects.\nCONCLUSIONS: GnRH-II antagonists seem to be suitable drugs for an efficacious and less-toxic endocrine therapy for breast cancers, including triple-negative breast cancers."}