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Pesquisa : E01.370.225.500.383.910 [Categoria DeCS]
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[PMID]:29352318
[Au] Autor:William D; Walther M; Schneider B; Linnebacher M; Classen CF
[Ad] Endereço:University Children's and Adolescents' Hospital, University Medicine of Rostock, Rostock, Germany.
[Ti] Título:Temozolomide-induced increase of tumorigenicity can be diminished by targeting of mitochondria in in vitro models of patient individual glioblastoma.
[So] Source:PLoS One;13(1):e0191511, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro. In this study, treatment of several primary GBM cell lines with clinically relevant doses of temozolomide increased their tumorigenicity as determined by colony formation assays in soft agar. Increased tumorigenicity is a known property of CSCs. Hence, therapy options that specifically target CSCs are under investigation. CSCs appear to be particularly dependent on mitochondria biogenesis which may represent a useful target for CSC elimination. Toxicity towards mitochondria is a known side effect of several antibiotics. Thus, addition of antibiotics like doxycycline may represent a useful tool to inhibit CSCs in GBM. Here, we show that combining temozolomide treatment of primary GBM cells with doxycycline could counteract the increase of tumorigenicity induced by temozolomide treatment.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/efeitos adversos
Neoplasias Encefálicas/tratamento farmacológico
Neoplasias Encefálicas/patologia
Dacarbazina/análogos & derivados
Glioblastoma/tratamento farmacológico
Glioblastoma/patologia
[Mh] Termos MeSH secundário: Antibacterianos/administração & dosagem
Antineoplásicos Alquilantes/administração & dosagem
Biomarcadores Tumorais/metabolismo
Neoplasias Encefálicas/metabolismo
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Metilases de Modificação do DNA/genética
Enzimas Reparadoras do DNA/genética
Dacarbazina/administração & dosagem
Dacarbazina/efeitos adversos
Doxiciclina/administração & dosagem
Resistência a Medicamentos Antineoplásicos
Fucosiltransferases/metabolismo
Glioblastoma/metabolismo
Seres Humanos
Antígeno Lewis X/metabolismo
Mitocôndrias/efeitos dos fármacos
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/metabolismo
Células-Tronco Neoplásicas/patologia
Nestina/metabolismo
Ensaio Tumoral de Célula-Tronco
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents, Alkylating); 0 (Biomarkers, Tumor); 0 (Lewis X Antigen); 0 (NES protein, human); 0 (Nestin); 0 (Tumor Suppressor Proteins); 7GR28W0FJI (Dacarbazine); EC 2.1.1.- (DNA Modification Methylases); EC 2.1.1.63 (MGMT protein, human); EC 2.4.1.- (FUT4 protein, human); EC 2.4.1.- (Fucosyltransferases); EC 6.5.1.- (DNA Repair Enzymes); N12000U13O (Doxycycline); YF1K15M17Y (temozolomide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191511


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[PMID]:28683444
[Au] Autor:Xiao W; Zheng J; Zhou B; Pan L
[Ad] Endereço:Department of Digestion, University-Town Hospital of Chongqing Medical University, Chongqing, China.
[Ti] Título:Replication Protein A 3 Is Associated with Hepatocellular Carcinoma Tumorigenesis and Poor Patient Survival.
[So] Source:Dig Dis;36(1):26-32, 2018.
[Is] ISSN:1421-9875
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Replication protein A (RPA) 3 is a subunit of the RPA protein complex, which functions in multiple processes of DNA metabolism. Dysregulation of RPA1 and RPA2 has been implicated in tumor progression in several cancer types. However, the function of RPA3 in hepatocellular carcinoma (HCC) tumorigenesis has not been elucidated. METHOD: In this study, we investigated the function of RPA3 in HCC development by stably knocking down its expression using short hairpin RNA (shRNA) in HepG2 cell line, followed by cell proliferation, colony formation, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumor-promoting properties of RPA3. RESULTS: Downregulation of RPA3-inhibited cell proliferation, colony formation, soft agar growth as well as invasion in HepG2 cells were observed. Stable knockdown of RPA3 significantly inhibited tumor growth in the xenograft mouse model. In addition, qRT-PCR analysis revealed that RPA3 was upregulated in human HCC tissues compared with matched noncancerous adjacent tissues (NATs). High expression of RPA3 was associated with poor overall survival and disease-free survival. CONCLUSION: Elevated expression of RPA3 promotes tumor progression in HCC cells. RPA3 is upregulated in HCC tissues and high expression of RPA3 is associated with poorer patient survival. Therefore, this protein may represent a novel therapeutic target for intervention of HCC and prognostic biomarker for patient survival.
[Mh] Termos MeSH primário: Carcinogênese/metabolismo
Carcinogênese/patologia
Carcinoma Hepatocelular/metabolismo
Carcinoma Hepatocelular/patologia
Proteínas de Ligação a DNA/metabolismo
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
[Mh] Termos MeSH secundário: Animais
Carcinogênese/genética
Carcinoma Hepatocelular/genética
Proliferação Celular
Transformação Celular Neoplásica/genética
Intervalo Livre de Doença
Regulação para Baixo/genética
Feminino
Regulação Neoplásica da Expressão Gênica
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/genética
Camundongos Nus
Meia-Idade
Invasividade Neoplásica
Ensaio Tumoral de Célula-Tronco
Regulação para Cima
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (RPA3 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1159/000478977


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[PMID]:29365412
[Au] Autor:Hu XL; Zhai YF; Li GD; Xing JF; Yang J; Bi YH; Wang J; Shi RY
[Ad] Endereço:Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China; Translational Medicine Research Center, Shanxi Medical University, Taiyuan 030001, China.
[Ti] Título:[FAT1 inhibits cell proliferation of esophageal squamous cell carcinoma through regulating the expression of CDK4/CDK6/CCND1 complex].
[So] Source:Zhonghua Zhong Liu Za Zhi;40(1):14-20, 2018 Jan 23.
[Is] ISSN:0253-3766
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To explore the expression of FAT1 in esophageal squamous cell carcinoma (ESCC) tissues, and its effect on cell proliferation. The expression levels of FAT1 protein in human ESCC tissues and matched adjacent normal tissues were determined by immunohistochemistry (IHC). Lentivirus based knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assays was performed to examine the effect of FAT1 on the proliferation of these ESCC cells. Colony formation assay was used to detect the colony formation ability. Flow cytometry was performed to analyze the cell cycle and apoptosis. The expression levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR) and Western blot. The relative expression of FAT1 in ESCC tissues was 66.97±21.53, significantly lower than 78.13±16.76 of adjacent normal tissues( <0.05). Knockdown of FAT1 promoted cell proliferation and colony formation. In YSE2 cell, the division time in negative control (NC) group was (1 570±51) min, significantly longer than (1 356±31) min in shFAT1 group. In Colo680N cell, division time in NC group was (1 532±53) min, significantly longer than (1 290±30) min in shFAT1 group ( <0.05). Knockdown of FAT1 promoted G1-to S-phase transition and resulted in the upregulation of CDK4/CDK6/CCND1. FAT1 inhibits the proliferation and G1-to S-phase transition of ESCC cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.
[Mh] Termos MeSH primário: Caderinas/fisiologia
Carcinoma de Células Escamosas/metabolismo
Carcinoma de Células Escamosas/patologia
Proliferação Celular
Ciclina D1/metabolismo
Quinase 4 Dependente de Ciclina/metabolismo
Quinase 6 Dependente de Ciclina/metabolismo
Neoplasias Esofágicas/metabolismo
Neoplasias Esofágicas/patologia
Regulação Neoplásica da Expressão Gênica
Proteínas de Neoplasias/fisiologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Esôfago/metabolismo
Fase G1
Técnicas de Silenciamento de Genes
Seres Humanos
Proteínas de Neoplasias/metabolismo
Fase S
Ensaio Tumoral de Célula-Tronco
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCND1 protein, human); 0 (Cadherins); 0 (FAT1 protein, human); 0 (Neoplasm Proteins); 136601-57-5 (Cyclin D1); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (CDK6 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 4); EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0253-3766.2018.01.003


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[PMID]:29049740
[Au] Autor:Doherty RE; Sisley K; Hammond DW; Rennie IG; Cross NA
[Ad] Endereço:Academic Unit of Ophthalmology and Orthoptics, Department of Oncology and Metabolism, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom.
[Ti] Título:Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5387-5395, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed "cancer stem cells" (CSCs). Methods: Expression of postulated stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in UM cell lines and primary UM short-term cultures (STCs) established from tumor samples. Additionally, the notion of a "cellular hierarchy" within UM was investigated. Finally, the phenomenon of phenotypic plasticity in response to environmental factors was explored. Results: We demonstrate that expression of ALDH, CD44, and CD133 does not select for a subpopulation of stem-like cells in either UM cell lines or UM STCs. Furthermore, there is an absence of a cellular hierarchy in cell lines and all cells in culture are able to drive tumor progression. Last, we show that established UM cell lines and UM STCs are plastic in nature and switch their phenotype in response to environmental stimuli. Conclusions: We hypothesize that this capacity to undergo phenotypic plasticity may be a consequence of neural crest lineage and renders the exploration of the CSC hypothesis extremely challenging in UM.
[Mh] Termos MeSH primário: Plasticidade Celular
Melanoma/patologia
Células-Tronco Neoplásicas/patologia
Neoplasias Uveais/patologia
[Mh] Termos MeSH secundário: Antígeno AC133/metabolismo
Aldeído Desidrogenase/metabolismo
Biomarcadores Tumorais/metabolismo
Linhagem Celular Tumoral
Citometria de Fluxo
Seres Humanos
Receptores de Hialuronatos/metabolismo
Melanoma/metabolismo
Células-Tronco Neoplásicas/metabolismo
Fenótipo
Ensaio Tumoral de Célula-Tronco
Neoplasias Uveais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AC133 Antigen); 0 (Biomarkers, Tumor); 0 (CD44 protein, human); 0 (Hyaluronan Receptors); 0 (PROM1 protein, human); EC 1.2.1.3 (Aldehyde Dehydrogenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22272


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[PMID]:28923203
[Au] Autor:Kwon H; Song K; Han C; Zhang J; Lu L; Chen W; Wu T
[Ad] Endereço:Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
[Ti] Título:Epigenetic Silencing of miRNA-34a in Human Cholangiocarcinoma via EZH2 and DNA Methylation: Impact on Regulation of Notch Pathway.
[So] Source:Am J Pathol;187(10):2288-2299, 2017 Oct.
[Is] ISSN:1525-2191
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aberrant expression and regulation of miRNAs have been implicated in multiple stages of tumorigenic processes. The current study was designed to explore the biological function and epigenetic regulation of miR-34a in human cholangiocarcinoma (CCA). Our data show that the expression of miR-34a is decreased significantly in CCA cells compared with non-neoplastic biliary epithelial cells. Forced overexpression of miR-34a in CCA cells inhibited their proliferation and clonogenic capacity in vitro, and suppressed tumor xenograft growth in severe combined immunodeficiency mice. We identified three key components of the Notch pathway, Notch1, Notch2, and Jagged 1, as direct targets of miR-34a. Our further studies show that down-regulation of miR-34a is caused by Enhancer of zeste homolog 2 (EZH2)-mediated H3 lysine 27 trimethylation as well as DNA methylation. Accordingly, treatment with the EZH2 inhibitor, selective S-adenosyl-methionine-competitive small-molecule (GSK126), or the DNA methylation inhibitor, 5-Aza-2'-deoxycytidine, partially restored miR-34a levels in human CCA cells. Immunohistochemical staining and Western blot analyses showed increased EZH2 expression in human CCA tissues and cell lines. We observed that GSK126 significantly reduced CCA cell growth in vitro and intrahepatic metastasis in vivo. Our findings provide novel evidence that miR-34a expression is silenced epigenetically by EZH2 and DNA methylation, which promotes CCA cell growth through activation of the Notch pathway. Consequently, these signaling cascades may represent potential therapeutic targets for effective treatment of human CCA.
[Mh] Termos MeSH primário: Neoplasias dos Ductos Biliares/genética
Colangiocarcinoma/genética
Metilação de DNA/genética
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo
Epigênese Genética
Inativação Gênica
MicroRNAs/metabolismo
Transdução de Sinais/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Neoplasias dos Ductos Biliares/patologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/genética
Colangiocarcinoma/patologia
Ilhas de CpG/genética
Metilação de DNA/efeitos dos fármacos
Proteína Potenciadora do Homólogo 2 de Zeste/genética
Epigênese Genética/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Inativação Gênica/efeitos dos fármacos
Histonas/metabolismo
Seres Humanos
Indóis/farmacologia
Lisina/metabolismo
Masculino
Camundongos Endogâmicos NOD
MicroRNAs/genética
Metástase Neoplásica
Piridonas/farmacologia
Receptores Notch/genética
Receptores Notch/metabolismo
Transdução de Sinais/efeitos dos fármacos
Ensaio Tumoral de Célula-Tronco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GSK126); 0 (Histones); 0 (Indoles); 0 (MIRN34 microRNA, human); 0 (MicroRNAs); 0 (Pyridones); 0 (Receptors, Notch); EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE


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[PMID]:28920959
[Au] Autor:Kuntz EM; Baquero P; Michie AM; Dunn K; Tardito S; Holyoake TL; Helgason GV; Gottlieb E
[Ad] Endereço:Cancer Research UK, Beatson Institute, Glasgow, UK.
[Ti] Título:Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells.
[So] Source:Nat Med;23(10):1234-1240, 2017 Oct.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs. We performed metabolic analyses on both stem cell-enriched (CD34 and CD34 CD38 ) and differentiated (CD34 ) cells derived from individuals with CML, and we compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, we demonstrate that primitive CML cells rely on upregulated oxidative metabolism for their survival. We also show that combination treatment with imatinib and tigecycline, an antibiotic that inhibits mitochondrial protein translation, selectively eradicates CML LSCs both in vitro and in a xenotransplantation model of human CML. Our findings provide a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Mesilato de Imatinib/farmacologia
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Minociclina/análogos & derivados
Mitocôndrias/efeitos dos fármacos
Células-Tronco Neoplásicas/efeitos dos fármacos
Fosforilação Oxidativa/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Sobrevivência Celular/efeitos dos fármacos
Cromatografia Líquida
Quimioterapia Combinada
Feminino
Seres Humanos
Hipoglicemiantes/farmacologia
Mesilato de Imatinib/uso terapêutico
Técnicas In Vitro
Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo
Espectrometria de Massas
Metabolômica
Camundongos
Camundongos Endogâmicos NOD
Minociclina/farmacologia
Mitocôndrias/metabolismo
Células-Tronco Neoplásicas/metabolismo
Fenformin/farmacologia
Inibidores de Proteínas Quinases/uso terapêutico
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Células Tumorais Cultivadas
Ensaio Tumoral de Célula-Tronco
Regulação para Cima
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Hypoglycemic Agents); 0 (Protein Kinase Inhibitors); 70JE2N95KR (tigecycline); 8A1O1M485B (Imatinib Mesylate); DD5K7529CE (Phenformin); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4399


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[PMID]:28898246
[Au] Autor:Popolin CP; Reis JPB; Becceneri AB; Graminha AE; Almeida MAP; Corrêa RS; Colina-Vegas LA; Ellena J; Batista AA; Cominetti MR
[Ad] Endereço:Departmento de Gerontologia, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
[Ti] Título:Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells.
[So] Source:PLoS One;12(9):e0183275, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1) [Ru(SO4)(dppb)(bipy)], (2) [Ru(CO3)(dppb)(bipy)], (3) [Ru(C2O4)(dppb)(bipy)] and (4) [Ru(CH3CO2)(dppb)(bipy)]PF6 [where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine], on proliferation of TNBC (MDA-MB-231), estrogen-dependent breast tumor cells (MCF-7) and a non-tumor breast cell line (MCF-10A). Complex (4) was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4) was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4) was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4) should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Complexos de Coordenação/farmacologia
Rutênio/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/química
Antineoplásicos/toxicidade
Apoptose/efeitos dos fármacos
Adesão Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Complexos de Coordenação/química
Complexos de Coordenação/toxicidade
Cristalografia por Raios X
DNA/química
DNA/metabolismo
Feminino
Seres Humanos
Espectroscopia de Ressonância Magnética
Modelos Moleculares
Conformação Molecular
Rutênio/química
Rutênio/toxicidade
Neoplasias de Mama Triplo Negativas
Ensaio Tumoral de Célula-Tronco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Coordination Complexes); 7UI0TKC3U5 (Ruthenium); 9007-49-2 (DNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183275


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[PMID]:28870926
[Au] Autor:Okuhashi Y; Itoh M; Tohda S
[Ad] Endereço:Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
[Ti] Título:Hedgehog Stimulation Suppresses Clonogenicity and Activates NOTCH Signalling in T-lymphoblastic Leukaemia Jurkat Cells.
[So] Source:Anticancer Res;37(9):5005-5009, 2017 09.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Hedgehog (HH) and NOTCH pathways are involved in the regulation of cancer stem cells and haematopoietic malignancies. However, the effects of HH stimulation on cell growth and NOTCH signalling in acute T-lymphoblastic leukaemia (T-ALL) cells have not been elucidated. MATERIALS AND METHODS: Two T-ALL cell lines, Jurkat and KOPT-K1 harbouring activating NOTCH1 mutations, were cultured with recombinant Sonic (S) HH and analysed for proliferation, colony formation, and expression of NOTCH-regulated genes and proteins. RESULTS: SHH stimulation did not affect cell growth but suppressed colony formation, increased the levels of cleaved NOTCH1 fragment characteristic for NOTCH1 activation, and upregulated mRNA expression of HES1, while decreasing that of MYC in Jurkat cells. However, no such effects were observed in KOPT-K1 cells. CONCLUSION: Our results indicate that SHH stimulation activates NOTCH signalling in Jurkat cells, thus disclosing a novel relationship between HH and NOTCH pathways.
[Mh] Termos MeSH primário: Proliferação Celular
Proteínas Hedgehog/metabolismo
Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia
Receptor Notch1/metabolismo
[Mh] Termos MeSH secundário: Apoptose
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Células Tumorais Cultivadas
Ensaio Tumoral de Célula-Tronco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hedgehog Proteins); 0 (NOTCH1 protein, human); 0 (Receptor, Notch1); 0 (SHH protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE


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[PMID]:28866101
[Au] Autor:Liu B; Li J; Zheng M; Ge J; Li J; Yu P
[Ad] Endereço:Department of Medical Oncology, Sichuan Cancer Hospital, Chengdu, China.
[Ti] Título:MiR-542-3p exerts tumor suppressive functions in non-small cell lung cancer cells by upregulating FTSJ2.
[So] Source:Life Sci;188:87-95, 2017 Nov 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Up-regulation or down-regulation of microRNAs (miRNAs) has been found in non-small cell lung cancer (NSCLC). However, the role and mechanism of regulation of miR-542-3p in NSCLC is still unclear. This study aimed at investigating the primary biological function of miR-542-3p and FTSJ2 in NSCLC tumorigenesis and the correlation of miR-542-3p and FTSJ2 in NSCLC. MAIN METHODS: Our present results showed that miR-542-3p was down-regulated in NSCLC tissues and cancer cells. Overexpression of miR-542-3p inhibited cell proliferation, cell migration, cell cycle, EMT process and tumor growth in vitro, and induced cell apoptosis by MTT assay, colony formation assay, transwell migration assay, flow cytometry assay, RT-qPCR assay, western blot experiment and vivo model assay; miR-542-3p directly bound to the 3'UTR of FTSJ2 and upregulated FTSJ2 both mRNA and protein level by EGFP reporter assay, RT-qPCR and western blot analysis in NSCLC cells. FTSJ2 also reduced the aggressiveness of NSCLC cells. KEY FINDINGS: In short, miR-542-3p functions as a suppressor gene by targeting and upregulating FTSJ2, thus inhibiting the malignancy of NSCLC cells. SIGNIFICANCE: According to the results, miRNA-542-3p and its targeted FTSJ2 may be indispensable as a predictive biomarker of the response to the treatment in patients with NSCLC.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Genes Supressores de Tumor
Neoplasias Pulmonares/metabolismo
Metiltransferases/genética
MicroRNAs/genética
Neoplasias/genética
Neoplasias/patologia
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Apoptose
Carcinoma Pulmonar de Células não Pequenas/genética
Pontos de Checagem do Ciclo Celular/fisiologia
Movimento Celular/fisiologia
Proliferação Celular/fisiologia
Regulação para Baixo
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Neoplasias Pulmonares/genética
Metiltransferases/biossíntese
MicroRNAs/metabolismo
Proteínas Nucleares/biossíntese
Ensaio Tumoral de Célula-Tronco
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN542 microRNA, human); 0 (MicroRNAs); 0 (Nuclear Proteins); EC 2.1.1.- (FTSJ2 protein, human); EC 2.1.1.- (Methyltransferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170904
[St] Status:MEDLINE


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[PMID]:28834297
[Au] Autor:Rodríguez-García A; Samsó P; Fontova P; Simon-Molas H; Manzano A; Castaño E; Rosa JL; Martinez-Outshoorn U; Ventura F; Navarro-Sabaté À; Bartrons R
[Ad] Endereço:Unitat de Bioquímica, Departament de Ciències Fisiològiques, IDIBELL, Universitat de Barcelona, Spain.
[Ti] Título:TGF-ß1 targets Smad, p38 MAPK, and PI3K/Akt signaling pathways to induce PFKFB3 gene expression and glycolysis in glioblastoma cells.
[So] Source:FEBS J;284(20):3437-3454, 2017 Oct.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In human cancers, transforming growth factor-ß1 (TGF-ß1) plays a dual role by acting as both a tumor suppressor and a promoter of tumor metastasis. Although TGF-ß1 contributes to the metabolic reprogramming of cancer cells and tumor-associated stromal cells, little is known of the molecular mechanisms connecting this cytokine with enhanced glycolysis. PFKFB3 is a homodymeric bifunctional enzyme, belonging to the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases, that controls the conversion of fructose-6-phosphate (Fru-6-P) to fructose-2,6-bisphosphate (Fru-2,6-P ). This metabolite is important for the dynamic regulation of glycolytic flux by allosterically activating phosphofructokinase-1, a rate-limiting enzyme in glycolysis. The PFKFB3 gene is involved in cell proliferation via its role in carbohydrate metabolism. Here, we studied the mechanisms connecting TGF-ß1, glucose metabolism, and PFKFB3 in glioblastoma cell lines. We demonstrate that TGF-ß1 upregulates PFKFB3 mRNA and protein expression resulting in an increase in fructose 2,6-bisphosphate concentration, glucose uptake, glycolytic flux and lactate production. Moreover, these increases in PFKFB3 mRNA and protein expression and Fru-2,6-P concentration were reduced when the Smad3, p38 mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were inhibited. We demonstrate that inhibition of PFKFB3 activity with 3PO or siRNA-mediated knockdown of PFKFB3 significantly eliminated the capacity of the T98G cells to form colonies by TGF-ß1, one of the hallmarks of transformation. Taken together, these results show that TGF-ß1 induces PFKFB3 expression through activation of the p38 MAPK and PI3K/Akt signaling pathways that complement and converge with early activation of Smad signaling. This suggests that PFKFB3 induction by TGF-ß1 can be one of the main mechanisms mediating the reprogramming of glioma cells.
[Mh] Termos MeSH primário: Glioblastoma/metabolismo
Glicólise/efeitos dos fármacos
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfofrutoquinase-2/metabolismo
Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores
Proteínas Smad/antagonistas & inibidores
Fator de Crescimento Transformador beta1/farmacologia
Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
[Mh] Termos MeSH secundário: Proliferação Celular/efeitos dos fármacos
Frutosedifosfatos/metabolismo
Glioblastoma/tratamento farmacológico
Glioblastoma/patologia
Glucose/metabolismo
Seres Humanos
Fosfatidilinositol 3-Quinases/metabolismo
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais/efeitos dos fármacos
Proteínas Smad/metabolismo
Células Tumorais Cultivadas
Ensaio Tumoral de Célula-Tronco
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fructosediphosphates); 0 (Smad Proteins); 0 (Transforming Growth Factor beta1); 79082-92-1 (fructose 2,6-diphosphate); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.105 (PFKFB3 protein, human); EC 2.7.1.105 (Phosphofructokinase-2); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14201



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