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[PMID]:29298343
[Au] Autor:Choi YJ; Park SJ; Park YS; Park HS; Yang KM; Heo K
[Ad] Endereço:Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea.
[Ti] Título:EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells.
[So] Source:PLoS One;13(1):e0190638, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC. We selected CD44 and EpCAM peptides that bind to HLA-A2 molecules on the basis of their binding affinity, as determined by a peptide-T2 binding assay. Our data showed that CSCs express high levels of tumor-associated antigens (TAAs) as well as major histocompatibility complex (MHC) molecules. Pulsing DCs with CD44 and EpCAM peptides resulted in the efficient generation of mature DCs (mDCs), thus enhancing T cell stimulation and generating potent cytotoxic T lymphocytes (CTLs). The activation of CSC peptide-specific immune responses by the DC vaccine in combination with standard chemotherapy may provide better clinical outcomes in advanced carcinomas.
[Mh] Termos MeSH primário: Vacinas Anticâncer/uso terapêutico
Carcinoma Hepatocelular/terapia
Células Dendríticas/imunologia
Molécula de Adesão da Célula Epitelial/administração & dosagem
Neoplasias Hepáticas/terapia
Fragmentos de Peptídeos/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Vacinas Anticâncer/imunologia
Carcinoma Hepatocelular/imunologia
Linhagem Celular Tumoral
Ensaio de Imunoadsorção Enzimática
Molécula de Adesão da Célula Epitelial/química
Feminino
Antígeno HLA-A2/imunologia
Xenoenxertos
Seres Humanos
Receptores de Hialuronatos/imunologia
Neoplasias Hepáticas/imunologia
Camundongos
Camundongos Endogâmicos BALB C
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cancer Vaccines); 0 (EPCAM protein, human); 0 (Epithelial Cell Adhesion Molecule); 0 (HLA-A2 Antigen); 0 (Hyaluronan Receptors); 0 (Peptide Fragments)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190638


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[PMID]:29245156
[Au] Autor:Alshaer W; Ababneh N; Hatmal M; Izmirli H; Choukeife M; Shraim A; Sharar N; Abu-Shiekah A; Odeh F; Al Bawab A; Awidi A; Ismail S
[Ad] Endereço:Cell Therapy Center, The University of Jordan, Amman, Jordan.
[Ti] Título:Selection and targeting of EpCAM protein by ssDNA aptamer.
[So] Source:PLoS One;12(12):e0189558, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aptamers are molecules that reveal highly complex and refined molecular recognition properties. These molecules are capable of binding with high affinity and selectivity to targets, ranging from small molecules to whole living cells. Several aptamers have been selected for targeting cellular proteins and they have also used in developing therapeutics and diagnostic strategies. Epithelial cell adhesion molecule (EpCAM) is considered as a cancer stem cell (CSC) biomarker and one of the most promising targets for aptamer selection against CSCs. In this study, we have developed a ssDNA aptamer with high affinity and selectivity of targeting the EpCAM protein extracellular domain. The SELEX technique was applied and the resulted sequences were tested on EpCAM-positive human gastric cancer cell line, KATO III, and the EpCAM-negative mouse embryonic fibroblast, NIH/3T3 cells. Ep1 aptamer was successfully isolated and showed selective binding on EpCAM-positive KATO III cells when compared to EpCAM-negative NIH/3T3 cells, as observed by the flow cytometry and the confocal imaging results. Additionally, the binding of Ep1 to EpCAM protein was assessed using mobility shifting assay and aptamers-protein docking. Furthermore, the binding affinity of Ep1 was measured against EpCAM protein using EpCAM-immobilized on magnetic beads and showed apparent affinity of 118 nM. The results of this study could suggest that Ep1 aptamer can bind specifically to the cellular EpCAM protein, making it an attractive ligand for targeted drug delivery and as an imaging agent for the identification of cancer cells.
[Mh] Termos MeSH primário: Aptâmeros de Nucleotídeos/química
Molécula de Adesão da Célula Epitelial/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Linhagem Celular Tumoral
Molécula de Adesão da Célula Epitelial/química
Seres Humanos
Camundongos
Simulação de Acoplamento Molecular
Células NIH 3T3
Conformação de Ácido Nucleico
Ligação Proteica
Técnica de Seleção de Aptâmeros
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aptamers, Nucleotide); 0 (EPCAM protein, human); 0 (Epithelial Cell Adhesion Molecule)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189558


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[PMID]:27773936
[Au] Autor:Liu Y; Qi Y; Bai ZH; Ni CX; Ren QH; Xu WH; Xu J; Hu HG; Qiu L; Li JZ; He ZG; Zhang JP
[Ad] Endereço:Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 310000, China.
[Ti] Título:A novel matrine derivate inhibits differentiated human hepatoma cells and hepatic cancer stem-like cells by suppressing PI3K/AKT signaling pathways.
[So] Source:Acta Pharmacol Sin;38(1):120-132, 2017 Jan.
[Is] ISSN:1745-7254
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, which has shown chemopreventive potential against various cancers. In this study, we evaluated the anticancer efficacy of a novel derivative of matrine, (6aS, 10S, 11aR, 11bR, 11cS)-10- methylamino-dodecahydro- 3a,7a-diazabenzo (de) (MASM), against human hepatocellular carcinoma (HCC) cells and their corresponding sphere cells in vitro and in vivo. Human HCC cell lines (Hep3B and Huh7) were treated with MASM. Cell proliferation was assessed using CCK8 and colony assays; cell apoptosis and cell cycle distributions were examined with flow cytometry. The expression of cell markers and signaling molecules was detected using Western blot and qRT-PCR analyses. A sphere culture technique was used to enrich cancer stem cells (CSC) in Hep3B and Huh7 cells. The in vivo antitumor efficacy of MASM was evaluated in Huh7 cell xenograft model in BALB/c nude mice, which were administered MASM (10 mg·kg ·d , ig) for 3 weeks. After the treatment was completed, tumor were excised and weighed. A portion of tumor tissue was enzymatically dissociated to obtain a single cell suspension for the spheroid formation assays. MASM (2, 10, 20 µmol/L) dose-dependently inhibited the proliferation of HCC cells, and induced apoptosis, which correlated with a reduction in Bcl-2 expression and an increase in PARP cleavage. MASM also induced cell cycle arrest in G /G phase, which was accompanied by increased p27 and decreased Cyclin D1 expression. Interestingly, MASM (2, 10, and 20 µmol/L) drastically reduced the EpCAM /CD133 cell numbers, suppressed the sphere formation, inhibited the expression of stem cell marker genes and promoted the expression of mature hepatocyte markers in the Hep3B and Huh7 spheroids. Additionally, MASM dose-dependently suppressed the PI3K/AKT/mTOR and AKT/GSK3ß/ß-catenin signaling pathways in Hep3B and Huh7 cells. In Huh7 xenograft bearing nude mice, MASM administration significantly inhibited Huh7 xenograft tumor growth and markedly reduced the number of surviving cancer stem-like cells in the tumors. MASM administration also reduced the expression of stem cell markers while increasing the expression of mature hepatocyte markers in the tumor tissues. The novel derivative of matrine, MASM, markedly suppresses HCC tumor growth through multiple mechanisms, and it may be a promising candidate drug for the treatment of hepatocellular carcinoma.
[Mh] Termos MeSH primário: Alcaloides/química
Alcaloides/farmacologia
Carcinoma Hepatocelular/patologia
Proliferação Celular/efeitos dos fármacos
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia
Neoplasias Hepáticas/patologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Quinolizinas/química
Quinolizinas/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Contagem de Células
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Diferenciação Celular
Linhagem Celular Tumoral
Ciclina D1/biossíntese
Relação Dose-Resposta a Droga
Molécula de Adesão da Célula Epitelial/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Camundongos
Camundongos Nus
Células-Tronco Neoplásicas/enzimologia
Células-Tronco Neoplásicas/metabolismo
Fosfatidilinositol 3-Quinases
Antígeno Nuclear de Célula em Proliferação/biossíntese
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-methylaminododecahydro-3a,7a-diazabenzo(de)anthracene-8-thione); 0 (Alkaloids); 0 (Antineoplastic Agents); 0 (EPCAM protein, human); 0 (Epithelial Cell Adhesion Molecule); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (Proliferating Cell Nuclear Antigen); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Quinolizines); 0 (p27 antigen); 136601-57-5 (Cyclin D1); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); N390W430AC (matrine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/aps.2016.104


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[PMID]:29031565
[Au] Autor:Wang L; Li Y; Xu J; Zhang A; Wang X; Tang R; Zhang X; Yin H; Liu M; Wang DD; Lin PP; Shen L; Dong J
[Ad] Endereço:Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China.
[Ti] Título:Quantified postsurgical small cell size CTCs and EpCAM circulating tumor stem cells with cytogenetic abnormalities in hepatocellular carcinoma patients determine cancer relapse.
[So] Source:Cancer Lett;412:99-107, 2018 Jan 01.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such "uncapturable and invisible" CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45 /CD31 ) in patients subjected to surgical resection. Clinical significance of diverse subtypes of CTC was systematically investigated. Existence of small cell size CTCs (≤5 µm of WBCs) with cytogenetic abnormality of aneuploid chromosome 8, which constituted majority of the detected CTCs in HCC patients, was demonstrated for the first time. The stemness marker EpCAM aneuploid circulating tumor stem cells (CTSCs), and EpCAM small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity of small triploid CTCs (≥5 cells/6 ml blood), multiploid (≥pentasomy 8) CTSCs or CTM (either one ≥ 1) significantly correlated to HCC patients' poor prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs in post-operative patients help predict neoplasm recurrence.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Aberrações Cromossômicas
Molécula de Adesão da Célula Epitelial/análise
Neoplasias Hepáticas/patologia
Recidiva Local de Neoplasia
Células Neoplásicas Circulantes
Células-Tronco Neoplásicas/fisiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Carcinoma Hepatocelular/genética
Feminino
Seres Humanos
Neoplasias Hepáticas/genética
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epithelial Cell Adhesion Molecule)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


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[PMID]:28972093
[Au] Autor:Cho Y; Kwon D; Kang SJ
[Ad] Endereço:Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
[Ti] Título:The Cooperative Role of CD326 and CD11b Dendritic Cell Subsets for a Hapten-Induced Th2 Differentiation.
[So] Source:J Immunol;199(9):3137-3146, 2017 Nov 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dendritic cells (DCs) play a critical role in directing immune responses. Previous studies have identified a variety of DC subsets and elucidated their context-dependent functions that parallel those of effector Th cell subsets. However, little is known about the DC subsets responsible for differentiation of Th2 cells governing allergic contact dermatitis. In this study, we sought to determine the DC subset(s) that mediate Th2 priming in hapten-sensitized mice. We induced hapten-specific Th2 differentiation by sensitizing the mice with a single application of FITC dissolved in acetone:dibutyl phthalate, and traced the immune cells responsible for inducing the Th2 differentiation process at the primary stimulation, enabling us to track Th2 priming in vivo and to delete basophils and specific DC subsets. Our analysis revealed that IL-4 was produced in vivo as early as day 3 from CD4 T cells with a single application of FITC. Basophils, despite producing IL-4 1 d earlier than T cells, were found to be dispensable for Th2 differentiation. Instead, we demonstrated that CD326 dermal DCs and Langerhans cells were redundantly required for FITC-induced Th2 differentiation in vivo. Moreover, the cooperation of CD326 Langerhans cells and CD11b DCs differentiated naive T cells into Th2 cells in vitro. Collectively, our findings highlight at least two DC subsets that play a critical role in polarizing naive CD4 T cells to Th2 cells and support a two-hit model for Th2 differentiation.
[Mh] Termos MeSH primário: Antígeno CD11b/imunologia
Diferenciação Celular/efeitos dos fármacos
Molécula de Adesão da Célula Epitelial/imunologia
Haptenos/farmacologia
Células de Langerhans/imunologia
Células Th2/imunologia
[Mh] Termos MeSH secundário: Animais
Antígeno CD11b/genética
Diferenciação Celular/genética
Diferenciação Celular/imunologia
Molécula de Adesão da Célula Epitelial/genética
Interleucina-4/genética
Interleucina-4/imunologia
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD11b Antigen); 0 (Epithelial Cell Adhesion Molecule); 0 (Haptens); 207137-56-2 (Interleukin-4)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601262


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[PMID]:28698144
[Au] Autor:Setiawan M; Tan XW; Goh TW; Hin-Fai Yam G; Mehta JS
[Ad] Endereço:Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore.
[Ti] Título:Inhibiting glycogen synthase kinase-3 and transforming growth factor-ß signaling to promote epithelial transition of human adipose mesenchymal stem cells.
[So] Source:Biochem Biophys Res Commun;490(4):1381-1388, 2017 Sep 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor ß (TGFß) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFß1 receptor kinase inhibitor), A-83-01 (TGFß type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h. The mesenchymal-epithelial transition was shown by down-regulation of mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin α5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin, Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin, deltaN p63 δNp63, Transcription Factor 4 TCF4 and Twist Family bHLH Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and stress fiber pattern were examined and the treated cells became less migratory in scratch wound closure assay. The formation of cell junction complexes was observed under transmission electron microscopy. Global gene expression using GeneChip Human Genome U133 Array (Affymetrix) showed that the treatment up-regulated 540 genes (containing genes for cell cycle, cytoskeleton reorganization, chemotaxis, epithelium development and regulation of cell migration) and down-regulated 483 genes. CONCLUSION: Human ADSCs were transited to epithelial lineage by inhibiting GSK3 and TGFß signaling. It can be an adult stem cell source for epithelial cell-based therapy.
[Mh] Termos MeSH primário: Adipócitos/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Quinase 3 da Glicogênio Sintase/genética
Células Mesenquimais Estromais/efeitos dos fármacos
Fator de Crescimento Transformador beta1/genética
Proteínas de Xenopus/genética
[Mh] Termos MeSH secundário: Adipócitos/citologia
Adipócitos/metabolismo
Tecido Adiposo/citologia
Tecido Adiposo/efeitos dos fármacos
Tecido Adiposo/metabolismo
Caderinas/genética
Caderinas/metabolismo
Movimento Celular/efeitos dos fármacos
Molécula de Adesão da Célula Epitelial/genética
Molécula de Adesão da Célula Epitelial/metabolismo
Regulação da Expressão Gênica
Quinase 3 da Glicogênio Sintase/antagonistas & inibidores
Quinase 3 da Glicogênio Sintase/metabolismo
Seres Humanos
Integrina alfa5/genética
Integrina alfa5/metabolismo
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/metabolismo
Ocludina/genética
Ocludina/metabolismo
Cultura Primária de Células
Pirazóis/farmacologia
Piridinas/farmacologia
Pirimidinas/farmacologia
Fatores de Transcrição da Família Snail/genética
Fatores de Transcrição da Família Snail/metabolismo
Tiossemicarbazonas/farmacologia
Fator de Crescimento Transformador beta1/antagonistas & inibidores
Fator de Crescimento Transformador beta1/metabolismo
Tranilcipromina/farmacologia
Tretinoína/farmacologia
Ácido Valproico/farmacologia
Vimentina/genética
Vimentina/metabolismo
Proteínas de Xenopus/antagonistas & inibidores
Proteínas de Xenopus/metabolismo
Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
Proteína da Zônula de Oclusão-1/genética
Proteína da Zônula de Oclusão-1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (A-83-01); 0 (CDH1 protein, human); 0 (Cadherins); 0 (Chir 99021); 0 (EPCAM protein, human); 0 (Enzyme Inhibitors); 0 (Epithelial Cell Adhesion Molecule); 0 (Integrin alpha5); 0 (OCLN protein, human); 0 (Occludin); 0 (Pyrazoles); 0 (Pyridines); 0 (Pyrimidines); 0 (RepSox); 0 (SNAI1 protein, human); 0 (Snail Family Transcription Factors); 0 (TJP1 protein, human); 0 (Thiosemicarbazones); 0 (Transforming Growth Factor beta1); 0 (Vimentin); 0 (Xenopus Proteins); 0 (ZEB1 protein, human); 0 (Zinc Finger E-box-Binding Homeobox 1); 0 (Zonula Occludens-1 Protein); 3E3V44J4Z9 (Tranylcypromine); 5688UTC01R (Tretinoin); 614OI1Z5WI (Valproic Acid); EC 2.7.11.26 (GSK3 protein, Xenopus); EC 2.7.11.26 (Glycogen Synthase Kinase 3)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE


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[PMID]:28668853
[Au] Autor:Athyala PK; Kanwar JR; Chitipothu S; Kanwar RK; Krishnakumar S; Watson JP; Narayanan J
[Ad] Endereço:Department of Nanobiotechnology, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Chennai, India.
[Ti] Título:Neocarzinostatin, Aptamer Conjugates for Targeting EpCAM-positive Tumor Cells.
[So] Source:Anticancer Res;37(7):3615-3629, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: The aim of this study was to investigate the role of Neocarzinostatin (NCS) conjugated with epithelial cell adhesion molecule (EpCAM) aptamer in EpCAM-positive cancer cells. NCS is an antitumor antibiotic protein chromophore that has the ability to cleave double stranded DNA and can be used as a potential drug for the treatment of EpCAM-positive cancers. EpCAM aptamer is an oligonucleotide ligand that binds specifically to EpCAM, a protein overexpressed in tumor cells. MATERIALS AND METHODS: NCS was conjugated with EpCAM aptamer using Sulfo-Succinimidyl 6-(3-(2-pyridyldithio) - propionamide hexanoate) LC-(SPDP) cross-linker to deliver it to EpCAM-positive tumor cells. The conjugates were characterized using polyacrylamide gel electrophoresis (PAGE) and high-performance liquid chromatography (HPLC). Flow cytometry was used to study the binding efficiency of the aptamer and the conjugates in cancer cells. The effect of the conjugate on cancer cells was studied using propidium iodide (PI) to analyze the cell cycle phase changes. The apoptosis assay was performed using the IC concentration of NCS. Microarrays were performed to study the gene level changes in cancer cells upon treatment with NCS and the conjugate. RESULTS: Flow cytometry revealed significant binding of aptamer and conjugate in the MCF-7 and WERI-Rb1 cell lines. Briefly, 62% in MCF and 30% in WERI-Rb1 cells with conjugate treated cells (p<0.005). The cell-cycle analysis indicated G phase arrest in MCF-7 cells and S phase arrest in WERI-Rb1 cells (p<0.005). Microarray analysis showed differentially expressed genes involved in cell cycle, DNA damage, and apoptosis. The BrDU assay and the apoptosis assay showed that the expression of BrDU was reduced in conjugate-treated cells and the PARP levels were increased confirming the double stranded DNA breaks (p<0.005). In MCF-7 and WERI-Rb1 cells, most of the cells underwent necrosis (p<0.005). CONCLUSION: The EpCAM aptamer conjugated NCS showed specificity to EpCAM-positive cells. The effect of the conjugates on cancer cells were impressive as the conjugate arrested the cell cycle and promoted apoptosis and necrosis. The high levels of PARP expression confirmed the DNA breaks upon conjugate treatment. Our study demonstrates that the NCS conjugated with EpCAM can be targeted to cancer cells sparing normal cells.
[Mh] Termos MeSH primário: Molécula de Adesão da Célula Epitelial/metabolismo
Neoplasias/tratamento farmacológico
Zinostatina/farmacologia
[Mh] Termos MeSH secundário: Antibióticos Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Quebras de DNA de Cadeia Dupla/efeitos dos fármacos
Dano ao DNA/efeitos dos fármacos
Seres Humanos
Células MCF-7
Neoplasias/metabolismo
Oligonucleotídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (EPCAM protein, human); 0 (Epithelial Cell Adhesion Molecule); 0 (Oligonucleotides); 9014-02-2 (Zinostatin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE


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[PMID]:28668851
[Au] Autor:Nagasato M; Rin Y; Yamamoto Y; Henmi M; Hiraoka N; Chiwaki F; Matsusaki K; Tagawa M; Sasaki H; Aoki K
[Ad] Endereço:Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
[Ti] Título:A Tumor-targeting Adenovirus with High Gene-transduction Efficiency for Primary Pancreatic Cancer and Ascites Cells.
[So] Source:Anticancer Res;37(7):3599-3605, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Optimizing targeting strategies for vectors in order to enhance antitumor activity and secure patient safety is important for cancer gene therapy. We previously identified two pancreatic cancer-targeting ligands (PFWSGAV: PFW and SYENFSA: SYE) by screening an adenovirus library in vivo and in vitro, respectively. MATERIALS AND METHODS: To examine clinical usefulness, we assessed gene-transduction efficiency using surgically-resected pancreatic cancer specimens and ascites cells. RESULTS: For surgical specimens, vectors displaying PFW and SYE improved transduction efficiency by 4.4- and 4.3-fold, respectively. The SYE-displaying vector was >2-fold more efficient for all seven cases, whereas the PFW-displaying vector increased efficiency in two out of four cases. For ascites samples, both vectors increased gene-transduction efficiency of epithelial cell adhesion molecule (EpCAM)-positive ascites cells by >2-fold in two out of five cases. CONCLUSION: Both vectors enhanced adenovirus infectivity of pancreatic cancer cells and have potential for gene therapy of pancreatic cancer; therefore they should be further evaluated in clinical studies.
[Mh] Termos MeSH primário: Adenoviridae/genética
Ascite/genética
Ascite/virologia
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/virologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Molécula de Adesão da Célula Epitelial/genética
Terapia Genética/métodos
Seres Humanos
Pâncreas/virologia
Transdução Genética/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epithelial Cell Adhesion Molecule)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE


  9 / 1275 MEDLINE  
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[PMID]:28668848
[Au] Autor:Seto K; Sakabe T; Itaba N; Azumi J; Oka H; Morimoto M; Umekita Y; Shiota G
[Ad] Endereço:Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
[Ti] Título:A Novel Small-molecule WNT Inhibitor, IC-2, Has the Potential to Suppress Liver Cancer Stem Cells.
[So] Source:Anticancer Res;37(7):3569-3579, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: The presence of cancer stem cells (CSCs) contributes to metastasis, recurrence, and resistance to chemo/radiotherapy in hepatocellular carcinoma (HCC). The WNT signaling pathway is reportedly linked to the maintenance of stemness of CSCs. In the present study, in order to eliminate liver CSCs and improve the prognosis of patients with HCC, we explored whether small-molecule compounds targeting WNT signaling pathway suppress liver CSCs. MATERIALS AND METHODS: The screening was performed using cell proliferation assay and reporter assay. We next investigated whether these compounds suppress liver CSC properties by using flow cytometric analysis and sphere-formation assays. A mouse xenograft model transplanted with CD44-positive HuH7 cells was used to examine the in vivo antitumor effect of IC-2. RESULTS: In HuH7 human HCC cells, 10 small-molecule compounds including novel derivatives, IC-2 and PN-3-13, suppressed cell viability and WNT signaling activity. Among them, IC-2 significantly reduced the CD44-positive population, also known as liver CSCs, and dramatically reduced the sphere-forming ability of both CD44-positive and CD44-negative HuH7 cells. Moreover, CSC marker-positive populations, namely CD90-positive HLF cells, CD133-positive HepG2 cells, and epithelial cell adhesion molecule-positive cells, were also reduced by IC-2 treatment. Finally, suppressive effects of IC-2 on liver CSCs were also observed in a xenograft model using CD44-positive HuH7 cells. CONCLUSION: The novel derivative of small-molecule WNT inhibitor, IC-2, has the potential to suppress liver CSCs and can serve as a promising therapeutic agent to improve the prognosis of patients with HCC.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma Hepatocelular/tratamento farmacológico
Neoplasias Hepáticas/tratamento farmacológico
Células-Tronco Neoplásicas/efeitos dos fármacos
Bibliotecas de Moléculas Pequenas/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Carcinoma Hepatocelular/metabolismo
Molécula de Adesão da Célula Epitelial/metabolismo
Células Hep G2
Xenoenxertos
Seres Humanos
Receptores de Hialuronatos/metabolismo
Fígado/efeitos dos fármacos
Fígado/metabolismo
Neoplasias Hepáticas/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Células-Tronco Neoplásicas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (CD44 protein, human); 0 (Epithelial Cell Adhesion Molecule); 0 (Hyaluronan Receptors); 0 (Small Molecule Libraries)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE


  10 / 1275 MEDLINE  
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[PMID]:28668827
[Au] Autor:Hayashi T; Yamashita T; Okada H; Oishi N; Sunagozaka H; Nio K; Hayashi T; Hara Y; Asahina Y; Yoshida M; Hashiba T; Suda T; Shirasaki T; Igarashi Y; Miyanouchi K; Yamashita T; Honda M; Kaneko S
[Ad] Endereço:Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
[Ti] Título:A Novel mTOR Inhibitor; Anthracimycin for the Treatment of Human Hepatocellular Carcinoma.
[So] Source:Anticancer Res;37(7):3397-3403, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Anthracimycin, a secondary metabolite of Streptomyces, has been shown to inhibit the invasion of certain cancer cell lines. MATERIALS AND METHODS: In this study we evaluated the effect of anthracimycin on cell growth and signaling pathways in hepatocellular carcinoma (HCC). RESULTS: Anthracimycin suppressed cell proliferation and motility and induced apoptosis in human HCC cell lines. Furthermore, anthracimycin had no effect on the enrichment of EpCAM-high liver cancer stem cells (CSCs), while fluorouracil dramatically enriched the CSCs with activation of the stemness-related genes EPCAM and SOX9 in HuH7 cells. Mechanistically, anthracimycin suppressed mammalian target of rapamycin (mTOR) signaling, and was most effective at inhibiting HCC cell proliferation with mTOR activation. CONCLUSION: Anthracimycin is a novel mTOR inhibitor capable of suppressing the proliferation of CSCs and non-CSCs equally well in HCC, and it is suggested that anthracimycin could be effective in the eradication of HCC associated with mTOR-signaling activation.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/tratamento farmacológico
Neoplasias Hepáticas/tratamento farmacológico
Policetídeos/farmacologia
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Carcinoma Hepatocelular/metabolismo
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Molécula de Adesão da Célula Epitelial/metabolismo
Fluoruracila/farmacologia
Seres Humanos
Neoplasias Hepáticas/metabolismo
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Epithelial Cell Adhesion Molecule); 0 (Polyketides); 0 (anthracimycin); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE



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