775 results on '"Bouillez A"'
Search Results
52. MUC1-C drives MYC in multiple myeloma
- Author
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Maroof Alam, Donald Kufe, Audrey Bouillez, Teru Hideshima, David Avigan, Reddy Gali, Yu-Tzu Tai, Kenneth C. Anderson, Hasan Rajabi, Ashujit Tagde, and Shannon T. Bailey
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0301 basic medicine ,Telomerase ,Transcription, Genetic ,Glutamate-Cysteine Ligase ,Immunology ,Down-Regulation ,Biology ,Response Elements ,Biochemistry ,digestive system ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D2 ,Transcription (biology) ,Cell Line, Tumor ,Gene silencing ,Humans ,skin and connective tissue diseases ,Transcription factor ,neoplasms ,beta Catenin ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Messenger RNA ,Lymphoid Neoplasia ,Mucin-1 ,Cell Biology ,Hematology ,TCF4 ,Molecular biology ,biological factors ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,CRISPR-Cas Systems ,Multiple Myeloma - Abstract
Multiple myeloma (MM) cell lines and primary tumor cells are addicted to the MYC oncoprotein for survival. Little is known, however, about how MYC expression is upregulated in MM cells. The mucin 1 C-terminal subunit (MUC1-C) is an oncogenic transmembrane protein that is aberrantly expressed in MM cell lines and primary tumor samples. The present studies demonstrate that targeting MUC1-C with silencing by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 editing or with the GO-203 inhibitor is associated with downregulation of MYC messenger RNA and protein. The results show that MUC1-C occupies the MYC promoter and thereby activates the MYC gene by a β-catenin/transcription factor 4 (TCF4)-mediated mechanism. In this way, MUC1-C (1) increases β-catenin occupancy on the MYC promoter, (2) forms a complex with β-catenin and TCF4, and, in turn, (3) drives MYC transcription. Analysis of MM cells using quantitative real-time reverse transcription polymerase chain reaction arrays further demonstrated that silencing MUC1-C is associated with downregulation of MYC target genes, including CCND2, hTERT, and GCLC Analysis of microarray data sets further demonstrated that MUC1 levels positively correlate with MYC expression in MM progression and in primary cells from over 800 MM patients. These findings collectively provide convincing evidence that MUC1-C drives MYC expression in MM.
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- 2015
53. Inhibition of MUC1-C Suppresses MYC Expression and Attenuates Malignant Growth in KRAS Mutant Lung Adenocarcinomas
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Ashujit Tagde, Akriti Kharbanda, Audrey Bouillez, Maroof Alam, Kwok-Kin Wong, Sean P. Pitroda, Caining Jin, Donald Kufe, and Hasan Rajabi
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Cell Survival ,Mice, Nude ,Adenocarcinoma of Lung ,Biology ,Adenocarcinoma ,medicine.disease_cause ,Article ,Cell Line ,Small hairpin RNA ,Proto-Oncogene Proteins c-myc ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Gene silencing ,Animals ,Humans ,RNA, Small Interfering ,Histone H3 acetylation ,EP300 ,neoplasms ,beta Catenin ,Mucin-1 ,Wnt signaling pathway ,TCF4 ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Wnt Proteins ,030104 developmental biology ,HEK293 Cells ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Female ,KRAS ,Signal transduction ,Peptides ,E1A-Associated p300 Protein ,Signal Transduction - Abstract
Dysregulation of MYC expression is a hallmark of cancer, but the development of agents that target MYC has remained challenging. The oncogenic MUC1-C transmembrane protein is, like MYC, aberrantly expressed in diverse human cancers. The present studies demonstrate that MUC1-C induces MYC expression in KRAS mutant non–small cell lung cancer (NSCLC) cells, an effect that can be suppressed by targeting MUC1-C via shRNA silencing, CRISPR editing, or pharmacologic inhibition with GO-203. MUC1-C activated the WNT/β-catenin (CTNNB1) pathway and promoted occupancy of MUC1-C/β-catenin/TCF4 complexes on the MYC promoter. MUC1-C also promoted the recruitment of the p300 histone acetylase (EP300) and, in turn, induced histone H3 acetylation and activation of MYC gene transcription. We also show that targeting MUC1-C decreased the expression of key MYC target genes essential for the growth and survival of NSCLC cells, such as TERT and CDK4. Based on these results, we found that the combination of GO-203 and the BET bromodomain inhibitor JQ1, which targets MYC transcription, synergistically suppressed MYC expression and cell survival in vitro as well as tumor xenograft growth. Furthermore, MUC1 expression significantly correlated with that of MYC and its target genes in human KRAS mutant NSCLC tumors. Taken together, these findings suggest a therapeutic approach for targeting MYC-dependent cancers and provide the framework for the ongoing clinical studies addressing the efficacy of MUC1-C inhibition in solid tumors. Cancer Res; 76(6); 1538–48. ©2016 AACR.
- Published
- 2015
54. Abstract 5047: The MUC1 membrane-bound mucin increases tumor cell properties and chemoresistance in renal clear cell carcinoma
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Brigitte Hémon, Justine Woszczyk, Michael Perrais, Jean-Baptiste Gibier, Kelly Gaudelot, Sébastien Aubert, Isabelle Van Seuningen, Audrey Bouillez, Mélanie Fanchon, and Viviane Gnemmi
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Oncology ,Cancer Research ,medicine.medical_specialty ,Matrigel ,Cell growth ,Mucin ,Cancer ,Transfection ,Biology ,medicine.disease ,Cell culture ,Internal medicine ,Cancer cell ,Cancer research ,medicine ,MUC1 - Abstract
Introduction: MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in renal clear-cell carcinomas (CRCC) with correlation to two major prognostic factors, Tumor-Node-Metastasis stage and nuclear Fürhman grade. Previously, we have shown that (i) MUC1 was significantly overexpressed in metastatic CRCC vs non-metastatic CRCC and (ii) MUC1 is a target gene of HIF-1 transcription factor which is a part of the hypoxia pathway, the main renal carcinogenetic pathway. Furthermore, CRCC is highly resistant to common systemic chemotherapies. Material and method: To better understand the roles of MUC1 in CRCC, we used two renal cell lines expressing MUC1 (786-O cells) or not (ACHN cells). 786-O cells were stably transfected with shRNA targeting MUC1 while ACHN cells with full-length MUC1. Proliferation, drug resistance, migration and invasion properties were studied in vitro in the different cellular clones using MTS cell proliferation assay, wound healing assay and Boyden chambers coated with Matrigel, respectively. Signaling pathways were screened by proteome profiler and western blot. Results and discussion: We showed that MUC1 expression was associated with increased invasion and migration properties of renal carcinomatous cells and a decrease of cell-cell interactions. MUC1 overexpressing cells (i) expressed higher levels of anti-apoptotic factors and MDR genes involved in chemoresistance processes and (ii) were more resistant to chemotherapeutic drugs. Conclusion: Our results show that MUC1 plays a role in biological properties of renal cancer cells suggesting important function for this mucin in tumour progression and chemo-resistance. Our data confirm its potential as a therapeutic target in this type of cancer. Citation Format: Kelly Gaudelot, Viviane Gnemmi, Audrey Bouillez, Jean-Baptiste Gibier, Mélanie Fanchon, Justine Woszczyk, Brigitte Hémon, Isabelle Van Seuningen, Sébastien Aubert, Michael Perrais. The MUC1 membrane-bound mucin increases tumor cell properties and chemoresistance in renal clear cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5047.
- Published
- 2016
55. MUC1 drives epithelial–mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter
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Isabelle Van Seuningen, Sébastien Aubert, Brigitte Hémon, Christelle Cauffiez, Kelly Gaudelot, Bélinda Ringot, David Bernard, Nicolas Pottier, Arnauld Villers, Michael Perrais, David Vindrieux, Xavier Leroy, Audrey Bouillez, Viviane Gnemmi, François Glowacki, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille
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Transcriptional Activation ,Cancer Research ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,[SDV]Life Sciences [q-bio] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Snail ,digestive system ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,biology.animal ,medicine ,Humans ,RNA, Messenger ,Epithelial–mesenchymal transition ,Promoter Regions, Genetic ,skin and connective tissue diseases ,Carcinoma, Renal Cell ,Wnt Signaling Pathway ,neoplasms ,Transcription factor ,beta Catenin ,MUC1 ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Cell Nucleus ,0303 health sciences ,biology ,Mucin-1 ,Wnt signaling pathway ,Kidney Neoplasms ,biological factors ,digestive system diseases ,Up-Regulation ,Wnt Proteins ,HEK293 Cells ,Oncology ,030220 oncology & carcinogenesis ,Catenin ,Cancer cell ,Cancer research ,Snail Family Transcription Factors ,Signal transduction ,Transcription Factors - Abstract
MUC1 is overexpressed in human carcinomas. The transcription factor SNAIL can activate epithelial-mesenchymal transition (EMT) in cancer cells. In this study, in renal carcinoma, we demonstrate that (i) MUC1 and SNAIL were overexpressed in human sarcomatoid carcinomas, (ii) SNAIL increased indirectly MUC1 expression, (iii) MUC1 overexpression induced EMT, (iv) MUC1 C-terminal domain (MUC1-C) and β-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/β-catenin signaling pathway activation and SNAIL expression. Altogether, our findings demonstrate that MUC1 is an actor in EMT and appears as a new therapeutic target.
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- 2014
56. Implication de la mucine membranaire MUC1 dans la progression tumorale rénale et identification de nouvelles cibles thérapeutiques
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Bouillez, Audrey, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université du Droit et de la Santé - Lille II, Michaël Perrais, and STAR, ABES
- Subjects
Cancer du rein ,Protéine ADAM ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Mucines ,MUC1 ,skin and connective tissue diseases ,digestive system ,neoplasms ,biological factors ,digestive system diseases ,Renal cell carcinoma ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Renal cell carcinoma corresponds to 5% of all adult malignancies and originates from renal tubules. The main histologic subtype is represented by clear renal cell carcinoma. Ninety percent of cRCC present a biallelic inactivation of the von Hippel Lindau (VHL) tumor suppressor gene resulting in constitutive activation of hypoxia signaling pathway via the Hypoxia Inducible Factor (HIF) -1 transcription factor that contributes to the physiology of tumours. cRCC is typically highly resistant to conventional systemic therapies. MUC1 is a membrane-anchored mucin and its cytoplasmic tail (CT) can interact with many signaling pathways and act as a co-transcription factor to activate genes involved in tumor progression and metastasis. Previous studies have shown that MUC1 is diffusely overexpressed in cRCC and MUC1 overexpression has been found to be associated with metastatic disease and a worse prognosis.MUC1 is overexpressed in renal cell carcinoma with correlation to prognosis and has been implicated in the hypoxic pathway, the main renal carcinogenetic pathway. In this context, we assessed the effects of MUC1 overexpression on renal cancer cells properties. Using shRNA strategy and/or different MUC1 constructs, we found that MUC1-extracellular domain and MUC1 CT are both involved in increase of migration, cell viability, resistance to anoikis and to decrease of cell aggregation in cancer cells. We also showed that MUC1 is involved in cRCC chemoresistance by inducing chemoresistance genes expression like ABCG2 and GSTO2. Invasiveness depends only on MUC1 CT. Then, by using siRNA strategy and/or pharmacological inhibitors or peptides, we showed that sheddases ADAM10, ADAM17 and gamma-secretase are necessary for MUC1 C-terminal subunit (MUC1-C) nuclear location and in increase of invasion property. Finally, MUC1 overexpression increases ADAM10/17 protein expression suggesting a positive regulatory loop. In conclusion, we report that MUC1 acts in renal cancer progression and MUC1-C nuclear localization is driving invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway. MUC1 appears as a therapeutic target by blocking MUC1 cleavage or nuclear translocation by using pharmacological approach and peptide strategies., Le carcinome rénal représente 5% des tumeurs de l’adulte et se développe au niveau des tubules rénaux. Le sous-type histologique majeur des cancers du rein est le carcinome rénal à cellules claires (cRCC). 90% des cRCC présentent une inactivation biallélique du gène suppresseur de tumeur de Von Hippel Lindau (VHL) induisant une activation constitutive de la voie de l’hypoxie via le facteur de transcription HIF1-α (Hypoxia Inducible Factor) qui contribue à la physiologie des tumeurs. Les cRCC sont des tumeurs à la fois radio- et chimiorésistantes, rendant la prise en charge thérapeutique des patients très difficile.Nos recherches consistaient en l’étude des rôles de la mucine membranaire MUC1, dont la queue cytoplasmique (MUC1 CT) peut interagir avec différentes voies de signalisation et agir en tant que co-activateur transcriptionnel de nombreux gènes impliqués dans la progression tumorale et la diffusion métastatique. Des travaux antérieurs réalisés au laboratoire montraient que la surexpression de MUC1 observée dans les cRCC était associée au statut métastatique des patients et marquait un mauvais pronostic. Cette surexpression de MUC1 est également impliquée dans la voie de l’hypoxie, voie majeure de la carcinogenèse rénale. Le premier objectif de l’étude était donc de déterminer les effets de la surexpression de MUC1 sur les propriétés des cellules de cRCC. Nous montrons ainsi que le domaine extracellulaire de MUC1 ainsi que sa partie cytoplasmique sont impliqués dans l’augmentation des capacités migratoires et de la viabilité des cellules cancéreuses rénales et qu’elle leur confère une résistance à l’anoïkis, programme de mort cellulaire déclenché lorsque la cellule perd ses contacts avec les cellules voisines ou avec la matrice extra-cellulaire et diminuent les propriétés d’agrégation des cellules tumorales. Nous montrons également que MUC1 est impliquée dans la chimiorésistance des cRCC en induisant l’expression de genes de chimiorésistance comme ABCG2 et GSTO2. Nous montrons par ailleurs que les propriétés invasives des cellules de cRCC sont exclusivement liées à MUC1 CT. Le deuxième objectif de l’étude était d’identifier les mécanismes moléculaires à l’origine du clivage de MUC1 CT. En utilisant différentes stratégies (siARN, inhibiteurs pharmacologiques et peptides), nous montrons pour la première fois que deux sheddases, ADAM10 et ADAM17 et la gamma secrétase sont nécessaires au clivage de MUC1 C, permettant ainsi sa délocalisation nucléaire et l’augmentation des propriétés invasives des cellules de cRCC. Enfin, nous montrons que la surexpression de MUC1 augmente l’expression protéique d’ADAM10/17, suggérant une boucle de régulation positive existant en conditions pathologiques.En conclusion, notre étude souligne le rôle de MUC1 dans la progression tumorale rénale et montre que la localisation nucléaire de MUC1-C est à l’origine de l’acquisition d’un phénotype invasif et chimiorésistant via l’action des sheddases ADAM10/17 et de la gamma secrétase. MUC1 apparait alors comme une cible thérapeutique potentielle intéressante dans la prise en charge des cRCC.
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- 2014
57. MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway
- Author
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Nicolas Sergeant, Brigitte Hémon, Nicolas Pottier, Viviane Gnemmi, Xavier Leroy, Bélinda Ringot, Sébastien Aubert, Audrey Bouillez, François Glowacki, Kelly Gaudelot, Malika Hamdane, Christelle Cauffiez, Isabelle Van Seuningen, Caroline Butruille, Michael Perrais, Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], VAN SEUNINGEN, ISABELLE, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Pôle de Biologie Pathologie Génétique [CHU Lille], Mucines Epitheliales : du Gene a la Fonction, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université des Sciences et Technologies (Lille 1) (USTL), Neuroendocrinologie et physiopathologie neuronale, Alzheimer & Tauopathies (Equipe 1), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, UMR837, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Nanotechnologie et d'Instrumentation Optique (LNIO), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université de Lille, Sciences et Technologies, Alzheimer & Tauopathies [JPArc], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut pour la Recherche sur le Cancer de Lille [U837 INSERM - IRCL], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
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ADAM10 ,[SDV]Life Sciences [q-bio] ,Mice, SCID ,γ-secretase ,Metastasis ,Mice ,0302 clinical medicine ,Anoikis ,skin and connective tissue diseases ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,ADAM17 ,kidney cancer ,invasion ,Kidney Neoplasms ,Cell aggregation ,3. Good health ,[SDV] Life Sciences [q-bio] ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Heterografts ,Signal Transduction ,Research Paper ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MUC1 ,Biology ,Transfection ,digestive system ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Line, Tumor ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,neoplasms ,Gamma secretase ,030304 developmental biology ,Cell Nucleus ,Mucin-1 ,Sheddase ,medicine.disease ,biological factors ,digestive system diseases ,Protein Subunits ,Tumor progression ,Cancer cell ,Cancer research ,Amyloid Precursor Protein Secretases - Abstract
International audience; MUC1 is a membrane-anchored mucin and its cytoplasmic tail (CT) can interact with many signaling pathways and act as a co-transcription factor to activate genes involved in tumor progression and metastasis. MUC1 is overexpressed in renal cell carcinoma with correlation to prognosis and has been implicated in the hypoxic pathway, the main renal carcinogenetic pathway. In this context, we assessed the effects of MUC1 overexpression on renal cancer cells properties. Using shRNA strategy and/or different MUC1 constructs, we found that MUC1-extracellular domain and MUC1-CT are involved in increase of migration, cell viability, resistance to anoikis and in decrease of cell aggregation in cancer cells. Invasiveness depends only on MUC1-CT. Then, by using siRNA strategy and/or pharmacological inhibitors or peptides, we showed that sheddases ADAM10, ADAM17 and gamma-secretase are necessary for MUC1 C-terminal subunit (MUC1-C) nuclear location and in increase of invasion property. Finally, MUC1 overexpression increases ADAM10/17 protein expression suggesting a positive regulatory loop. In conclusion, we report that MUC1 acts in renal cancer progression and MUC1-C nuclear localization drives invasiveness of cancer cells through a sheddase/gamma secretase dependent pathway. MUC1 appears as a therapeutic target by blocking MUC1 cleavage or nuclear translocation by using pharmacological approach and peptide strategies.
- Published
- 2014
58. Synthesis of an enantiopure thioester as key substrate for screening the sensitivity of penicillin binding proteins to inhibitors
- Author
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Simon, Justine F., primary, Bouillez, André, additional, Frère, Jean-Marie, additional, Luxen, André, additional, and Zervosen, Astrid, additional
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- 2016
- Full Text
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59. Abstract 5047: The MUC1 membrane-bound mucin increases tumor cell properties and chemoresistance in renal clear cell carcinoma
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Gaudelot, Kelly, primary, Gnemmi, Viviane, additional, Bouillez, Audrey, additional, Gibier, Jean-Baptiste, additional, Fanchon, Mélanie, additional, Woszczyk, Justine, additional, Hémon, Brigitte, additional, Van Seuningen, Isabelle, additional, Aubert, Sébastien, additional, and Perrais, Michael, additional
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- 2016
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- View/download PDF
60. MUC1-C induces DNA methyltransferase 1 and represses tumor suppressor genes in acute myeloid leukemia
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Tagde, Ashujit, primary, Rajabi, Hasan, additional, Stroopinsky, Dina, additional, Gali, Reddy, additional, Alam, Maroof, additional, Bouillez, Audrey, additional, Kharbanda, Surender, additional, Stone, Richard, additional, Avigan, David, additional, and Kufe, Donald, additional
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- 2016
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61. Inhibition of MUC1-C Suppresses MYC Expression and Attenuates Malignant Growth in KRAS Mutant Lung Adenocarcinomas
- Author
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Bouillez, Audrey, primary, Rajabi, Hasan, additional, Pitroda, Sean, additional, Jin, Caining, additional, Alam, Maroof, additional, Kharbanda, Akriti, additional, Tagde, Ashujit, additional, Wong, Kwok-Kin, additional, and Kufe, Donald, additional
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- 2016
- Full Text
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62. Isolation and characterization of a primary proximal tubular epithelial cell model from human kidney by CD10/CD13 double labeling
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Cynthia Van der Hauwaert, Xavier Leroy, Laurent Zini, Grégoire Savary, Patrice Maboudou, Viviane Gnemmi, Michael Perrais, Audrey Bouillez, Nicolas Pottier, Christelle Cauffiez, François Glowacki, and Sébastien Aubert
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Pathology ,Anatomy and Physiology ,lcsh:Medicine ,Cell Separation ,Nephrectomy ,Kidney Tubules, Proximal ,0302 clinical medicine ,Molecular Cell Biology ,Electric Impedance ,lcsh:Science ,Cells, Cultured ,0303 health sciences ,Kidney ,education.field_of_study ,Multidisciplinary ,medicine.diagnostic_test ,Cell sorting ,Flow Cytometry ,medicine.anatomical_structure ,Phenotype ,Nephrology ,030220 oncology & carcinogenesis ,Medicine ,Neprilysin ,Cellular Types ,Research Article ,medicine.medical_specialty ,Cell type ,Cell Physiology ,Population ,Primary Cell Culture ,Biology ,CD13 Antigens ,Flow cytometry ,03 medical and health sciences ,medicine ,Humans ,education ,Cell Shape ,030304 developmental biology ,Renal Physiology ,Staining and Labeling ,lcsh:R ,Epithelial Cells ,Renal System ,Epithelium ,Cell culture ,Renal physiology ,lcsh:Q ,Cytometry - Abstract
Renal proximal tubular epithelial cells play a central role in renal physiology and are among the cell types most sensitive to ischemia and xenobiotic nephrotoxicity. In order to investigate the molecular and cellular mechanisms underlying the pathophysiology of kidney injuries, a stable and well-characterized primary culture model of proximal tubular cells is required. An existing model of proximal tubular cells is hampered by the cellular heterogeneity of kidney; a method based on cell sorting for specific markers must therefore be developed. In this study, we present a primary culture model based on the mechanical and enzymatic dissociation of healthy tissue obtained from nephrectomy specimens. Renal epithelial cells were sorted using co-labeling for CD10 and CD13, two renal proximal tubular epithelial markers, by flow cytometry. Their purity, phenotypic stability and functional properties were evaluated over several passages. Our results demonstrate that CD10/CD13 double-positive cells constitute a pure, functional and stable proximal tubular epithelial cell population that displays proximal tubule markers and epithelial characteristics over the long term, whereas cells positive for either CD10 or CD13 alone appear to be heterogeneous. In conclusion, this study describes a method for establishing a robust renal proximal tubular epithelial cell model suitable for further experimentation.
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- 2012
63. Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C
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Alexandre Herman, André Luxen, Ana Maria Amoroso, André Bouillez, Astrid Zervosen, Bernard Joris, Eric Sauvage, and Paulette Charlier
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Penicillin binding proteins ,medicine.drug_class ,Clinical Biochemistry ,Antibiotics ,Pharmaceutical Science ,medicine.disease_cause ,Biochemistry ,Microbiology ,Structure-Activity Relationship ,Antibiotic resistance ,Drug Discovery ,Streptococcus pneumoniae ,Actinomycetales ,polycyclic compounds ,medicine ,Penicillin-Binding Proteins ,Actinomadura ,Molecular Biology ,chemistry.chemical_classification ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Boronic Acids ,Penicillin ,Enzyme ,Molecular Medicine ,Bacteria ,medicine.drug - Abstract
In response to the widespread use of β-lactam antibiotics bacteria have evolved drug resistance mechanisms that include the production of resistant Penicillin Binding Proteins (PBPs). Boronic acids are potent β-lactamase inhibitors and have been shown to display some specificity for soluble transpeptidases and PBPs, but their potential as inhibitors of the latter enzymes is yet to be widely explored. Recently, a (2,6-dimethoxybenzamido)methylboronic acid was identified as being a potent inhibitor of Actinomadura sp. R39 transpeptidase (IC50: 1.3 μM). In this work, we synthesized and studied the potential of a number of acylaminomethylboronic acids as inhibitors of PBPs from different classes. Several derivatives inhibited PBPs of classes A, B and C from penicillin sensitive strains. The (2-nitrobenzamido)methylboronic acid was identified as a good inhibitor of a class A PBP (PBP1b from Streptococcus pneumoniae, IC50 = 26 μM), a class B PBP (PBP2xR6 from Streptococcus pneumoniae, IC50 = 138 μM) and a class C PBP (R39 from Actinomadura sp., IC50 = 0.6 μM). This work opens new avenues towards the development of molecules that inhibit PBPs, and eventually display bactericidal effects, on distinct bacterial species.
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- 2012
64. MUC1-C nuclear localization drives invasiveness of renal cancer cells through a sheddase/gamma secretase dependent pathway
- Author
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Bouillez, Audrey, primary, Gnemmi, Viviane, additional, Gaudelot, Kelly, additional, Hémon, Brigitte, additional, Ringot, Bélinda, additional, Pottier, Nicolas, additional, Glowacki, François, additional, Butruille, Caroline, additional, Cauffiez, Christelle, additional, Hamdane, Malika, additional, Sergeant, Nicolas, additional, Seuningen, Isabelle Van, additional, Leroy, Xavier, additional, Aubert, Sébastien, additional, and Perrais, Michaël, additional
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- 2014
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65. MUC1-C activates EZH2 expression and function in human cancer cells
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Rajabi, Hasan, Hiraki, Masayuki, Tagde, Ashujit, Alam, Maroof, Bouillez, Audrey, Christensen, Camilla L., Samur, Mehmet, Wong, Kwok-Kin, and Kufe, Donald
- Abstract
The EZH2 histone methyltransferase is a member of the polycomb repressive complex 2 (PRC2) that is highly expressed in diverse human cancers and is associated with a poor prognosis. MUC1-C is an oncoprotein that is similarly overexpressed in carcinomas and has been linked to epigenetic regulation. A role for MUC1-C in regulating EZH2 and histone methylation is not known. Here, we demonstrate that targeting MUC1-C in diverse human carcinoma cells downregulates EZH2 and other PRC2 components. MUC1-C activates (i) the EZH2 promoter through induction of the pRB→E2F pathway, and (ii) an NF-κB p65 driven enhancer in exon 1. We also show that MUC1-C binds directly to the EZH2 CXC region adjacent to the catalytic SET domain and associates with EZH2 on the CDH1 and BRCA1 promoters. In concert with these results, targeting MUC1-C downregulates EZH2 function as evidenced by (i) global and promoter-specific decreases in H3K27 trimethylation (H3K27me3), and (ii) activation of tumor suppressor genes, including BRCA1. These findings highlight a previously unreported role for MUC1-C in activating EZH2 expression and function in cancer cells.
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- 2017
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66. Isolation and Characterization of a Primary Proximal Tubular Epithelial Cell Model from Human Kidney by CD10/CD13 Double Labeling
- Author
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Van der Hauwaert, Cynthia, primary, Savary, Grégoire, additional, Gnemmi, Viviane, additional, Glowacki, François, additional, Pottier, Nicolas, additional, Bouillez, Audrey, additional, Maboudou, Patrice, additional, Zini, Laurent, additional, Leroy, Xavier, additional, Cauffiez, Christelle, additional, Perrais, Michaël, additional, and Aubert, Sébastien, additional
- Published
- 2013
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67. Protected Silver Coating for NIF Flashlamp Reflectors*
- Author
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Norman Thomas, Jesse Wolfe, Joseph Farmer, Al Erlandson, Chris Marshall, Dan Woodruff, Dan Bouillez, Darin Glenn, and Erik Bjornard
- Abstract
The National Ignition Facility at Lawrence Livermore National Laboratory will be a national center to study inertial confinement fusion and the physics of high energy and pressure. The $1.2 billion project consists of 192 laser beams which will direct more than 500 trillion watts towards a tiny target in a pulse only a billionth of a second long. The laser contains neodymium glass amplifiers which are pumped by xenon flashlamps. The flashlamps have silver reflectors to direct the light toward the glass laser slabs. Silver is ideal because of its high reflectance from 400 to 1000 nm wavelength which matches the neodymium absorption cross-section. In order to maintain the overall efficiency of the laser beams, there is an effort to prevent the corrosion of the silver reflectors by various means. One solution is the use of durable protected silver coatings which must survive 24,000 exposures to intense flashlamp light over a 30-year period while being exposed to small levels of atmospheric corrodants. One protected silver reflector has survived 20,717 flashlamp discharges so far in 100% Livermore atmosphere with no change in reflectance. This paper describes another protected silver reflector which is very durable.
- Published
- 1997
68. 344 The MUC1 Membrane-bound Mucin is an Actor in Renal Clear-cell Carcinoma
- Author
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Bouillez, A., primary, Butruille, C., additional, Ringot, B., additional, Gnemmi, V., additional, Van Seuningen, I., additional, Zini, L., additional, Leroy, X., additional, Aubert, A., additional, and Perrais, M., additional
- Published
- 2012
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69. Unexpected Tricovalent Binding Mode of Boronic Acids within the Active Site of a Penicillin-Binding Protein
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Zervosen, Astrid, primary, Herman, Raphael, additional, Kerff, Frédéric, additional, Herman, Alexandre, additional, Bouillez, André, additional, Prati, Fabio, additional, Pratt, R. F., additional, Frère, Jean-Marie, additional, Joris, Bernard, additional, Luxen, André, additional, Charlier, Paulette, additional, and Sauvage, Eric, additional
- Published
- 2011
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70. Abstract 2737: The MUC1 membrane-bound mucin is an actor in renal tumor progression
- Author
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Bouillez, Audrey, primary, Gnemmi, Viviane, additional, Butruille, Caroline, additional, Ringot, Bélinda, additional, Hémon, Brigitte, additional, van Seuningen, Isabelle, additional, Zini, Laurent, additional, Leroy, Xavier, additional, Aubert, Sébastien, additional, and Perrais, Michael, additional
- Published
- 2011
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71. Abstract 5250: MUC1 expression is induced by Snai1 in an epithelial mesenchymal transition renal model
- Author
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Gnemmi, Viviane, primary, Bouillez, Audrey, additional, Ringot, Bélinda, additional, Zini, Laurent, additional, Copin, Marie-Christine, additional, VanSeuningen, Isabelle, additional, Leroy, Xavier, additional, Perrais, Michael, additional, and Sébastien, Aubert, additional
- Published
- 2011
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72. 344 The MUC1 Membrane-bound Mucin is an Actor in Renal Clear-cell Carcinoma
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Bélinda Ringot, Laurent Zini, Audrey Bouillez, A. Aubert, Michael Perrais, Caroline Butruille, Xavier Leroy, Viviane Gnemmi, and I. Van Seuningen
- Subjects
Oncology ,Renal clear cell carcinoma ,Cancer Research ,medicine.medical_specialty ,Membrane bound ,Chemistry ,Internal medicine ,Mucin ,Cancer research ,medicine ,MUC1 - Published
- 2012
73. Abstract 2457: The MUC1 membrane-bound mucin is an actor in renal clear-cell carcinoma
- Author
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Bouillez, Audrey, primary, Gnemmi, Viviane, additional, Hémon, Brigitte, additional, Seuningen, Isabelle Van, additional, Zini, Laurent, additional, Leroy, Xavier, additional, Aubert, Sébastien, additional, and Perrais, Michael, additional
- Published
- 2010
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74. Abstract 2737: The MUC1 membrane-bound mucin is an actor in renal tumor progression
- Author
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Bélinda Ringot, Caroline Butruille, Audrey Bouillez, Brigitte Hémon, Michael Perrais, Laurent Zini, Sébastien Aubert, Xavier Leroy, Viviane Gnemmi, and Isabelle Van Seuningen
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Mucin ,Cancer ,Transfection ,Biology ,medicine.disease ,digestive system ,biological factors ,digestive system diseases ,Metastasis ,Flow cytometry ,Oncology ,Tumor progression ,Cancer cell ,Cancer research ,medicine ,skin and connective tissue diseases ,neoplasms ,MUC1 - Abstract
MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear-cell carcinomas (cRCC) with correlation to two prognostic factors, tumor-node metastasis stage and nuclear Fürhman grade. Previously (Aubert et al, Cancer Res 2009), we have shown that MUC1 was significantly overexpressed in metastatic cRCC vs non-metastatic cRCC and MUC1 is a target gene of HIF-1 transcription factor which is a part of the hypoxia pathway, the main renal carcinogenetic pathway. To better understand the roles of MUC1 in cRCC, we used two renal cell lines expressing MUC1 (Caki-2) or not (ACHN cells). Caki-2 cells were stably transfected with shRNA targeting MUC1 and ACHN cells with an expressing vector containing MUC1 cDNA. Flow cytometry assay and confocal microscopy showed a homogenous membrane expression of MUC1 but also in the nucleus. In vitro studies underlined MUC1 role in the invasion, migration and anchorage-independent growth. In contrast, MUC1 had no role in proliferation and clonogenicity. Cellular agreggation test showed that MUC1 expression is associated with a decrease of cell-cell interactions. Phospho-JNK and phospho-p38 levels were higher in MUC1 expressing cells. Transcriptomic analysis results performed on 44K Agilent Microarrays suggest that MUC1 is a candidate in chemoresistance. Subcutaneous xenograft will be also performed. Our results show that MUC1 plays a role in biological properties of renal cancer cells suggesting the important function for this mucin in tumor progression and confirms its potential as a therapeutic target in this type of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2737. doi:10.1158/1538-7445.AM2011-2737
- Published
- 2011
75. Abstract 5250: MUC1 expression is induced by Snai1 in an epithelial mesenchymal transition renal model
- Author
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Laurent Zini, Michael Perrais, Bélinda Ringot, Aubert Sébastien, Xavier Leroy, Audrey Bouillez, Isabelle Van-Seuningen, Marie-Christine Copin, and Viviane Gnemmi
- Subjects
Cancer Research ,Tissue microarray ,Mesenchymal stem cell ,Cancer ,Biology ,medicine.disease ,digestive system diseases ,Chromatin ,Oncology ,SNAI1 ,Cancer research ,medicine ,Epithelial–mesenchymal transition ,Sarcomatoid carcinoma ,neoplasms ,MUC1 - Abstract
Accumulating data suggest that epithelial mesenchymal transition (EMT) is involved in cancer progression. Sarcomatoid carcinoma represents a high-grade transformation and an EMT-like pattern. Up to 8% of conventional renal cells cancers (cRCC) present with sarcomatoid carcinoma component that portends a worse prognosis. MUC1, a membrane-bound glycoprotein is known to be over-expressed in cRCC with correlation to prognosis. Indeed, we showed that MUC1 overexpression is correlated with a metastatic phenotype using tissue microarray sampling 27 cRCC of same TNM stage. Also, we demonstrated in a series of 15 RCC with sarcomatoid component, the loss of epithelial markers and the acquisition of mesenchymal markers compared to conventional carcinomatous areas. MUC1 was significantly overexpressed along with Snai1, a major actor of EMT, in sarcomatoid component. So, we hypothesized that MUC1 could be regulated by Snai1. Bioinformatic analyses revealed two Snai1 E-boxes at -84/-72 on MUC1 promoter. Cotransfection studies of MUC1 promoter and Snai1 expression vectors in renal cells lines showed an induction of MUC1 transcriptional activity by luciferase assays. Mutagenesis site-directed of both Snai1 E-boxes in renal cells lines induced loss MUC1 transcriptional activity. By chromatin immunoprecipation assay and gel shift analysis we will demonstrate a direct interaction between Snai1 and MUC1 promoter. In conclusion, all these data revealed that MUC1, usually considered as an epithelial marker, is overexpressed during cancer linked EMT process with a direct regulation by Snai1 suggesting that MUC1 plays a role in renal cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5250. doi:10.1158/1538-7445.AM2011-5250
- Published
- 2011
76. Abstract 2457: The MUC1 membrane-bound mucin is an actor in renal clear-cell carcinoma
- Author
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Brigitte Hémon, Laurent Zini, Viviane Gnemmi, Michael Perrais, Audrey Bouillez, Xavier Leroy, Sébastien Aubert, and Isabelle Van Seuningen
- Subjects
Cancer Research ,Matrigel ,Pathology ,medicine.medical_specialty ,Cell growth ,business.industry ,Cancer ,Transfection ,medicine.disease ,Oncology ,Cell culture ,Apoptosis ,Cancer cell ,medicine ,Cancer research ,business ,MUC1 - Abstract
MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in renal clear-cell carcinomas (CRCC) with correlation to two major prognostic factors, Tumor-Node-Metastasis stage and nuclear Fürhman grade. Previously (Aubert et al., Cancer Res 2009), we have shown that (i) MUC1 was significantly overexpressed in metastatic CRCC vs non-metastatic CRCC and (ii) MUC1 is a target gene of HIF-1 transcription factor which is a part of the hypoxia pathway, the main renal carcinogenetic pathway. To better understand the roles of MUC1 in CRCC, we used two renal cell lines expressing MUC1 (Caki-2 cells) or not (ACHN cells). Caki-2 cells were stably transfected with shRNA targeting MUC1 and ACHN cells with an expressing vector containing MUC1 cDNA. Proliferation, migration and invasion properties were studied in vitro in the different cellular clones using Boyden chambers coated with Matrigel, wound healing assay and MTS cell proliferation assay, respectively. Our results showed that (i) MUC1 expression was associated with an increase of invasion and migration properties of renal carcinoma cells whereas no effect on proliferation and apoptotic rate was observed and (ii) levels of phospho-JNK were higher in MUC1 expressing cells. Results of (i) transcriptomic analysis on 44K Agilent microarrays, (ii) signaling pathway screening and (iii) subcutaneous xenografts will be presented. Our results show that MUC1 plays a role in biological properties of renal cancer cells suggesting important function for this mucin in tumour progression and confirms its potential as a therapeutic target in this type of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2457.
- Published
- 2010
77. MUC1-C ACTIVATES BMI1 IN HUMAN CANCER CELLS
- Author
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Hiraki, Masayuki, Maeda, Takahiro, Bouillez, Audrey, Alam, Maroof, Tagde, Ashujit, Hinohara, Kunihiko, Suzuki, Yozo, Markert, Tahireh, Miyo, Masaaki, Komura, Kazumasa, Ahmad, Rehan, Rajabi, Hasan, and Kufe, Donald
- Subjects
MUC1-C ,BMI1 ,PRC1 ,H2A ,HOXC5 ,HOXC13 ,p16 - Abstract
BMI1 is a component of the PRC1 complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells. In addition, we show that MUC1-C blocks miR-200c-mediated downregulation of BMI1 expression. The functional significance of this MUC1-C→BMI1 pathway is supported by the demonstration that targeting MUC1-C suppresses BMI1-induced ubiquitylation of H2A and thereby derepresses homeobox HOXC5 and HOXC13 gene expression. Notably, our results further show that MUC1-C binds directly to BMI1 and promotes occupancy of BMI1 on the CDKN2A promoter. In concert with BMI1-induced repression of the p16INK4a tumor suppressor, we found that targeting MUC1-C is associated with induction of p16INK4a expression. In support of these results, analysis of three gene expresssion datasets demonstrated highly significant correlations between MUC1-C and BMI1 in breast cancers. These findings uncover a previously unrecognized role for MUC1-C in driving BMI1 expression and in directly interacting with this stem cell factor, linking MUC1-C with function of the PRC1 in epigenetic gene silencing.
- Published
- 2016
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78. Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance.
- Author
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Singh D and Siddique HR
- Subjects
- Humans, Epithelial-Mesenchymal Transition genetics, Cell Transformation, Neoplastic, Phenotype, Tumor Microenvironment, Neoplasms pathology
- Abstract
Cancer cells undergo phenotypic switching (cancer cell plasticity) in response to microenvironmental cues, including exposure to therapy/treatment. Phenotypic plasticity enables the cancer cells to acquire more mesenchymal traits promoting cancer cells' growth, survival, therapy resistance, and disease recurrence. A significant program in cancer cell plasticity is epithelial-to-mesenchymal transition (EMT), wherein a comprehensive reprogramming of gene expression occurs to facilitate the translational shift from epithelial-to-mesenchymal phenotypes resulting in increased invasiveness and metastasis. In addition, EMT plays a pivotal role in facilitating cancer cells' escape from the body's immune system using several mechanisms, such as the downregulation of major histocompatibility complex-mediated antigen presentation, upregulation of immune checkpoint molecules, and recruitment of immune-suppressive cells. Cancer cells' ability to undergo phenotypic switching and EMT-driven immune escape presents a formidable obstacle in cancer management, highlighting the need to unravel the intricate mechanisms underlying these processes and develop novel therapeutic strategies. This article discusses the role of EMT in promoting immune evasion and therapy resistance. We also discuss the ongoing research on developing therapeutic approaches targeting intrinsic and induced cell plasticity within the immune suppressive microenvironment. We believe this review article will update the current research status and equip researchers, clinicians, and other healthcare professionals with valuable insights enhancing their existing knowledge and shedding light on promising directions for future cancer research. This will facilitate the development of innovative strategies for managing therapy-resistant cancers and improving patient outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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79. Toward a novel metal based chemotherapy against tropical diseases 4. Synthesis and characterization of new metal-clotrimazole complexes and evaluation of their activity against Trypanosoma cruzi
- Author
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Sánchez-Delgado, Roberto A., primary, Navarro, Maribel, additional, Lazardi, Keyla, additional, Atencio, Reinaldo, additional, Capparelli, Mario, additional, Vargas, Franklin, additional, Urbina, Julio A., additional, Bouillez, André, additional, Noels, Alfred F., additional, and Masi, Dante, additional
- Published
- 1998
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- View/download PDF
80. Protected Silver Coating for NIF Flashlamp Reflectors*
- Author
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Thomas, Norman, primary, Wolfe, Jesse, additional, Farmer, Joseph, additional, Erlandson, Al, additional, Marshall, Chris, additional, Woodruff, Dan, additional, Bouillez, Dan, additional, Glenn, Darin, additional, and Bjornard, Erik, additional
- Published
- 1997
- Full Text
- View/download PDF
81. Monocyte subsets in breast cancer patients under treatment with aromatase inhibitor and mucin-1 cancer vaccine.
- Author
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Knöbl, Viktoria, Maier, Lukas, Grasl, Stefan, Kratzer, Carmen, Winkler, Felix, Eder, Vanessa, Hayden, Hubert, Sahagun Cortez, Maria Amparo, Sachet, Monika, Oehler, Rudolf, Frantal, Sophie, Fesl, Christian, Zehetner, Karin, Pfeiler, Georg, Bartsch, Rupert, Fitzal, Florian, Singer, Christian F., Filipits, Martin, Gnant, Michael, and Brostjan, Christine
- Subjects
CANCER vaccines ,HORMONE therapy ,AROMATASE inhibitors ,ESTROGEN receptors ,NEOADJUVANT chemotherapy - Abstract
Background: Monocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models. Methods: To elucidate whether changes in monocyte subsets are associated with treatment and response, we investigated peripheral blood samples of 73 postmenopausal women with estrogen receptor (ER) positive BC, who received aromatase inhibitor therapy with or without the mucin-1 vaccine tecemotide in the ABCSG34 trial. Blood was retrieved at baseline, midterm and end of therapy, and was analyzed for the distribution and ER expression of monocyte subsets by flow cytometry. Results: When 40 healthy, age-matched women were compared with BC patients before treatment start, ER levels of monocytes did not differ, yet patients presented with a higher frequency of classical and fewer non-classical monocytes. Endocrine therapy triggered a significant increase in ER levels in all monocyte subsets, without affecting subset distribution. Vaccination had no overall impact on subset frequency and ER expression. Yet, a shift from intermediate to classical monocytes during therapy correlated with changes in plasma cytokines and chemokines and was significantly associated with low residual cancer burden in vaccinated patients. Without tecemotide, baseline ER levels in classical monocytes were significantly higher in women with good response to endocrine therapy. Conclusions: This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
82. Biosynthesis of multifunctional transformable peptides for downregulation of PD-L1.
- Author
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Di, Yufei, Yang, Zhiwen, Song, Gang, Shen, Qi, Bai, Haotian, Huang, Yiming, Lv, Fengting, and Wang, Shu
- Subjects
IMMUNE checkpoint proteins ,CATHEPSIN B ,BIOSYNTHESIS ,PEPTIDES ,PROGRAMMED death-ligand 1 - Abstract
Here, we present a biosynthesized material M1 for immune checkpoint blocking therapy. M1 could realize a morphological transformation from globular to fibrous in situ in the presence of cathepsin B (CtsB) after entering tumor cells. The GO203 peptides of M1 are exposed, which could bind to mucin 1 (MUC1) to suppress the homodimerization process of MUC1, thereby downregulating PD-L1 expression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
83. Advances in MUC1 resistance to chemotherapy in pancreatic cancer.
- Author
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Yao, Youhao and Fan, Daguang
- Published
- 2024
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84. RUNX1-MUC13 Interaction Activates Wnt/β-Catenin Signaling Implications for Colorectal Cancer Metastasis.
- Author
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Xinyi Chen, Jingyao Tu, Mu Yang, Yuan Wang, Bo Liu, Hong Qiu, and Xianglin Yuan
- Published
- 2024
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- View/download PDF
85. Inhibition of α4β1 Integrin Activity by Small Tellurium Compounds Regulates PD-L1 Expression and Enhances Antitumor Effects.
- Author
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Chaouat, Abigael, Kalechman, Yona, Hay, Ophir, Manoim, Julia E., Lantner, Tal, Niderberg, Eitan, Hauschner, Hagit, Sredni, Dvora Kenigsbuch, Cohen, Tal, Schlesinger, Agata, Nadler, Ronia, Barda-Saad, Mira, Noy, Elad, Albeck, Michael, Longo, Dan L., and Sredni, Benjamin
- Published
- 2024
- Full Text
- View/download PDF
86. The multifaceted role of MUC1 in tumor therapy resistance.
- Author
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Jin W, Zhang M, Dong C, Huang L, and Luo Q
- Subjects
- Humans, Cell Line, Tumor, Mucin-1 genetics
- Abstract
Tumor therapeutic resistances are frequently linked to the recurrence and poor prognosis of cancers and have been a key bottleneck in clinical tumor treatment. Mucin1 (MUC1), a heterodimeric transmembrane glycoprotein, exhibits abnormally overexpression in a variety of human tumors and has been confirmed to be related to the formation of therapeutic resistance. In this review, the multifaceted roles of MUC1 in tumor therapy resistance are summarized from aspects of pan-cancer principles shared among therapies and individual mechanisms dependent on different therapies. Concretely, the common mechanisms of therapy resistance across cancers include interfering with gene expression, promoting genome instability, modifying tumor microenvironment, enhancing cancer heterogeneity and stemness, and activating evasion and metastasis. Moreover, the individual mechanisms of therapy resistance in chemotherapy, radiotherapy, and biotherapy are introduced. Last but not least, MUC1-involved therapy resistance in different types of cancers and MUC1-related clinical trials are summarized., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Published
- 2023
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87. Structural basis of Pseudomonas aeruginosa penicillin binding protein 3 inhibition by the siderophore-antibiotic cefiderocol.
- Author
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Smith, Helen G., Basak, Shyam, Aniebok, Victor, Beech, Matthew J., Alshref, Faisal M., Allen, Mark D., Farley, Alistair J. M., and Schofield, Christopher J.
- Published
- 2024
- Full Text
- View/download PDF
88. The Rhône Parade.
- Author
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Cristaldi, Jonathan
- Published
- 2019
89. Cross-Talks between Raf Kinase Inhibitor Protein and Programmed Cell Death Ligand 1 Expressions in Cancer: Role in Immune Evasion and Therapeutic Implications.
- Author
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Ho, Mai and Bonavida, Benjamin
- Subjects
PROTEIN kinase inhibitors ,TUMOR suppressor genes ,CYTOTOXIC T cells ,LIGANDS (Biochemistry) ,IMMUNE checkpoint inhibitors ,TRANSCRIPTION factors - Abstract
Innovations in cancer immunotherapy have resulted in the development of several novel immunotherapeutic strategies that can disrupt immunosuppression. One key advancement lies in immune checkpoint inhibitors (ICIs), which have shown significant clinical efficacy and increased survival rates in patients with various therapy-resistant cancers. This immune intervention consists of monoclonal antibodies directed against inhibitory receptors (e.g., PD-1) on cytotoxic CD8 T cells or against corresponding ligands (e.g., PD-L1/PD-L2) overexpressed on cancer cells and other cells in the tumor microenvironment (TME). However, not all cancer cells respond—there are still poor clinical responses, immune-related adverse effects, adaptive resistance, and vulnerability to ICIs in a subset of patients with cancer. This challenge showcases the heterogeneity of cancer, emphasizing the existence of additional immunoregulatory mechanisms in many patients. Therefore, it is essential to investigate PD-L1's interaction with other oncogenic genes and pathways to further advance targeted therapies and address resistance mechanisms. Accordingly, our aim was to investigate the mechanisms governing PD-L1 expression in tumor cells, given its correlation with immune evasion, to uncover novel mechanisms for decreasing PD-L1 expression and restoring anti-tumor immune responses. Numerous studies have demonstrated that the upregulation of Raf Kinase Inhibitor Protein (RKIP) in many cancers contributes to the suppression of key hyperactive pathways observed in malignant cells, alongside its broadening involvement in immune responses and the modulation of the TME. We, therefore, hypothesized that the role of PD-L1 in cancer immune surveillance may be inversely correlated with the low expression level of the tumor suppressor Raf Kinase Inhibitor Protein (RKIP) expression in cancer cells. This hypothesis was investigated and we found several signaling cross-talk pathways between the regulations of both RKIP and PD-L1 expressions. These pathways and regulatory factors include the MAPK and JAK/STAT pathways, GSK3β, cytokines IFN-γ and IL-1β, Sox2, and transcription factors YY1 and NFκB. The pathways that upregulated PD-L1 were inhibitory for RKIP expression and vice versa. Bioinformatic analyses in various human cancers demonstrated the inverse relationship between PD-L1 and RKIP expressions and their prognostic roles. Therefore, we suspect that the direct upregulation of RKIP and/or the use of targeted RKIP inducers in combination with ICIs could result in a more targeted anti-tumor immune response—addressing the therapeutic challenges related to PD-1/PD-L1 monotherapy alone. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
90. MUC1 promotes cervical squamous cell carcinoma through ERK phosphorylation-mediated regulation of ITGA2/ITGA3.
- Author
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Zhao, Aiqin, Pan, Yunzhi, Gao, Yingyin, Zhi, Zheng, Lu, Haiying, Dong, Bei, Zhang, Xuan, Wu, Meiying, Zhu, Fenxia, Zhou, Sufang, and Ma, Sai
- Subjects
SQUAMOUS cell carcinoma ,DRUG target ,OVERALL survival ,CERVICAL cancer ,DEVELOPED countries - Abstract
In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA
2/3 , in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future. Summary: MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
91. XIST and MUC1-C form an auto-regulatory pathway in driving cancer progression.
- Author
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Wang, Keyi, Bhattacharya, Atrayee, Haratake, Naoki, Daimon, Tatsuaki, Nakashoji, Ayako, Ozawa, Hiroki, Peng, Bo, Li, Wei, and Kufe, Donald
- Published
- 2024
- Full Text
- View/download PDF
92. Toward a novel metal based chemotherapy against tropical diseases 4. Synthesis and characterization of new metal-clotrimazole complexes and evaluation of their activity against Trypanosoma cruzi
- Author
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Dante Masi, Franklin Vargas, André Bouillez, Maribel Navarro, M. V. Capparelli, Reinaldo Atencio, Keyla Lazardi, Julio A. Urbina, Alfred F. Noels, and Roberto A. Sánchez-Delgado
- Subjects
biology ,Clotrimazole ,Chemistry ,Stereochemistry ,Ligand ,Triclinic crystal system ,biology.organism_classification ,Inorganic Chemistry ,Metal ,Crystallography ,chemistry.chemical_compound ,visual_art ,Materials Chemistry ,visual_art.visual_art_medium ,medicine ,Imidazole ,Orthorhombic crystal system ,Physical and Theoretical Chemistry ,Trypanosoma cruzi ,medicine.drug ,Monoclinic crystal system - Abstract
The syntheses and characterization of metal imidazole complexes showing activity against Trypanosoma cruzi, the causative agent of Chagas disease, are presented, RuCl2(CTZ)2 (2) and RuCl2(BTZ)2 (4) were prepared by reaction of RuCl2(NCCH3)4 (1) with the appropriate ligand (CTZ, clotrimazole = 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole; BTZ = 1-[(2-bromophenyl)diphenylmethyl]-1H-imidazole) [Ru(bipy)(CTZ)2](PF6)2 (3) (bipy=2,2′-bipyridyl) was obtained by reaction of 2 with bipy and NH4PF6 in MeCN. Reaction of [RhCl(COD)]2 with CTZ yielded RhCl(COD)(CTZ) (5) (COD=1,5-cyclooctadiene), while AuCl1CTZ (6), K2[PtCl4(CTZ)2] (7) and [Cu(CTZ)2]PF6 (8) were obtained by interaction of CTZ with AuCl1·HCl, K2PtCl4 and [Cu(CH3CN)4]PF6, respectively. All the new complexes were characterized by NMR and other appropriate techniques, X-ray diffraction studies of 4·3H2O, 5 and 6 were also carried out. The structure of 4·3H2O consists of a distorted tetrahedral arrangement of two N atoms from the BTZ ligands and two Cl atoms around the Ru(II) ion; 4·3H2O crystallizes in the orthorhombic space group Puma (No. 62) with a=12.818(5), b=29.115(5), c=12.040(5) A , V=4493.2(8) A and Z=4. Complex 5 displayed a square planar structure typical for Rh(1) bound to N from CTZ, Cl, and the two CC bonds of COD; 5 crystallized in the triclinic space group (P(= l) (No. 2) with a=12.407(3), b=12.876(4), c=10.069(3) A , α=111.59(2)°, β=107.80(2)°, γ=103.28(2)°, V=1313.4(8) A 3 and Z=2. Complex 6 also displayed a square arrangement of N from CTZ, plus three Cl atoms around the Au(III) ion; 6 crystallized in the monoclinic space group P21/n (No. 14) with a=9.507(1), b=18.280(4), c=12.877(1) A , β=100.59(1)°, V=2199.7(5) A 3 and Z=4. All the new compounds were found to be active against in vitro cultures of Trypanosoma cruzi, following the trend 3 = 7
93. Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors.
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Chen, Tong, Wang, Mingzhao, Chen, Yanchao, and Liu, Yutao
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CELLULAR therapy ,CHIMERIC antigen receptors - Abstract
The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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94. Changes in the Expression of DNMTs Before and After Treatment with Methotrexate (MTX)/Mercaptopurine (6-MP) in B-Cell ALL Children.
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Imanei-Avaz, Mahmoud, Hashemi, Azam Sadat, Ghasemi, Nasrin, Hekmati Moghaddam, Seyed Hossein, Pourrajab, Fatemeh, Barzegar, Kazem, and Vakili, Mahmood
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DNA methyltransferases ,METHOTREXATE ,TUMOR suppressor genes ,STEM cell treatment ,CHILD patients ,PRELEUKEMIA ,ECTOPIC pregnancy - Abstract
Background: DNA methylation is catalyzed by DNA methyltransferases (DNMTs) which are encoded by DNMT1, DNMT3A, and DNMT3B. DNMTs play a major role in the abnormal methylation of tumor suppressors and cancer-related genes. Herein, this study explored the expression profile of DNMTs in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), before and after methotrexate (MTX)/mercaptopurine (6-MP) treatment. Materials and Methods: This before-after prospective study included 30 matched children in sex and age (20 children with B-cell ALL and 10 healthy children used as a control or calibrator group). The expression profile of DNMTs was assessed at two-time points; at the diagnosis time and after MTX/6-MP treatment in the consolidation-maintenance phase of therapy. Notable, all pediatric patients included in this study continued the therapy without adverse events, except two children who were excluded from the study. Results: The average age of the patient group was 7.1 ± 1.3 years (in the range of 4-9 years), and the average age of the control group was 8.3 ± 1.7 years (6-10 years). The expression profile of DNMTs in B-cell ALL children was obtained completely different from that in the healthy group. After MTX/6-MP treatment of B-cell ALL children, the expression levels of DNMT1 and 3A were increased (p <0.01 & 0.04, respectively), and the expression level of DNMT3B was decreased (p <0.01), significantly. Conclusions: In ALL, the expression profile of DNMTs would be changed whereby contribute to abnormal growth and maturation capacity of leukemic stem cells and MTX/6-MP treatment could reverse this profile from a cancerous phenotype to the normal one. [ABSTRACT FROM AUTHOR]
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- 2024
95. Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.
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Jiang, Yuan-Hong, Liu, Yu-Shu, Wei, Yu-Chung, Jhang, Jia-Fong, Kuo, Hann-Chorng, Huang, Hsin-Hui, Chan, Michael W. Y., Lin, Guan-Ling, Cheng, Wen-Chi, Lin, Shu-Chuan, and Wang, Hung-Jung
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BLADDER cancer ,TUMOR markers ,MACHINE learning ,DNA methylation ,RECEIVER operating characteristic curves - Abstract
Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings. [ABSTRACT FROM AUTHOR]
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- 2024
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96. The Role of MUC1 in Renal Cell Carcinoma.
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Milella, Martina, Rutigliano, Monica, Lasorsa, Francesco, Ferro, Matteo, Bianchi, Roberto, Fallara, Giuseppe, Crocetto, Felice, Pandolfo, Savio Domenico, Barone, Biagio, d'Amati, Antonio, Spilotros, Marco, Battaglia, Michele, Ditonno, Pasquale, and Lucarelli, Giuseppe
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RENAL cell carcinoma ,CANCER cell proliferation ,METABOLIC reprogramming ,CYTOLOGY ,RENAL cancer - Abstract
Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC. [ABSTRACT FROM AUTHOR]
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- 2024
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97. Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance.
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Singh, Deepti and Siddique, Hifzur R.
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Cancer cells undergo phenotypic switching (cancer cell plasticity) in response to microenvironmental cues, including exposure to therapy/treatment. Phenotypic plasticity enables the cancer cells to acquire more mesenchymal traits promoting cancer cells' growth, survival, therapy resistance, and disease recurrence. A significant program in cancer cell plasticity is epithelial-to-mesenchymal transition (EMT), wherein a comprehensive reprogramming of gene expression occurs to facilitate the translational shift from epithelial-to-mesenchymal phenotypes resulting in increased invasiveness and metastasis. In addition, EMT plays a pivotal role in facilitating cancer cells' escape from the body's immune system using several mechanisms, such as the downregulation of major histocompatibility complex–mediated antigen presentation, upregulation of immune checkpoint molecules, and recruitment of immune-suppressive cells. Cancer cells' ability to undergo phenotypic switching and EMT-driven immune escape presents a formidable obstacle in cancer management, highlighting the need to unravel the intricate mechanisms underlying these processes and develop novel therapeutic strategies. This article discusses the role of EMT in promoting immune evasion and therapy resistance. We also discuss the ongoing research on developing therapeutic approaches targeting intrinsic and induced cell plasticity within the immune suppressive microenvironment. We believe this review article will update the current research status and equip researchers, clinicians, and other healthcare professionals with valuable insights enhancing their existing knowledge and shedding light on promising directions for future cancer research. This will facilitate the development of innovative strategies for managing therapy-resistant cancers and improving patient outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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98. From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.
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Yibin Zhou, Fenglan Wang, Guangda Li, Jing Xu, Jingjing Zhang, Gullen, Elizabeth, Jie Yang, and Jing Wang
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IMMUNE checkpoint proteins ,NATURAL products ,TRADITIONAL medicine ,LUNG cancer ,IMMUNE checkpoint inhibitors - Abstract
Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy's effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy. [ABSTRACT FROM AUTHOR]
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- 2024
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99. Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis.
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Medina-Dols, Aina, Cañellas, Guillem, Capó, Toni, Solé, Montse, Mola-Caminal, Marina, Cullell, Natalia, Jaume, Marina, Nadal-Salas, Laura, Llinàs, Jaume, Gómez, Lluis, Tur, Silvia, Jiménez, Carmen, Díaz, Rosa M., Carrera, Caty, Muiño, Elena, Gallego-Fabrega, Cristina, Soriano-Tárraga, Carolina, Ruiz-Guerra, Laura, Pol-Fuster, Josep, and Asensio, Víctor
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- 2024
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100. MUC1 and MUC16: critical for immune modulation in cancer therapeutics.
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Xinyi Chen, Sandrine, Ineza Karambizi, Mu Yang, Jingyao Tu, and Xianglin Yuan
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IMMUNOREGULATION ,CELLULAR signal transduction ,TUMOR markers ,TUMOR microenvironment ,CANCER treatment - Abstract
The Mucin (MUC) family, a range of highly glycosylated macromolecules, is ubiquitously expressed in mammalian epithelial cells. Such molecules are pivotal in establishing protective mucosal barriers, serving as defenses against pathogenic assaults. Intriguingly, the aberrant expression of specific MUC proteins, notably Mucin 1 (MUC1) and Mucin 16 (MUC16), within tumor cells, is intimately associated with oncogenesis, proliferation, and metastasis. This association involves various mechanisms, including cellular proliferation, viability, apoptosis resistance, chemotherapeutic resilience, metabolic shifts, and immune surveillance evasion. Due to their distinctive biological roles and structural features in oncology, MUC proteins have attracted considerable attention as prospective targets and biomarkers in cancer therapy. The current review offers an exhaustive exploration of the roles of MUC1 and MUC16 in the context of cancer biomarkers, elucidating their critical contributions to the mechanisms of cellular signal transduction, regulation of immune responses, and the modulation of the tumor microenvironment. Additionally, the article evaluates the latest advances in therapeutic strategies targeting these mucins, focusing on innovations in immunotherapies and targeted drugs, aiming to enhance customization and accuracy in cancer treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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