A5032163349- Colorectal Cancer Treatments and Studies
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Radiopharmaceutical Chemistry and Applications
- Systemic Lupus Erythematosus Research
- Nanoplatforms for cancer theranostics
- T-cell and B-cell Immunology
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Radiomics and Machine Learning in Medical Imaging
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- Photodynamic Therapy Research Studies
- 3D Printing in Biomedical Research
- Lung Cancer Research Studies
Cancer Genetics (United States)
2006-2014
National Cancer Institute
2003-2014
Center for Cancer Research
2007-2014
Université Paris Cité
2012
Sorbonne Paris Cité
2012
Inserm
1996-2012
Hôpital Saint-Louis
2012
Assistance Publique – Hôpitaux de Paris
2012
Institut Curie
2012
Servier (France)
2012
Abstract Purpose: Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and advanced preclinical models. Our consortium joins efforts extensively develop characterize a new collection patient-derived colorectal cancer (CRC) Experimental Design: From 85 unsupervised surgical samples collection, 54 tumors were successfully xenografted in immunodeficient mice rats, representing 35 primary tumors, 5 peritoneal carcinoses 14 metastases. Histologic...
In humans, the molecular mechanisms underlying ovarian follicle endowment and activation, which are closely related to control of female reproduction, occurrence menopause, diseases such as premature failure, poorly understood. current study, we provide several lines genetic evidence that cyclin-dependent kinase (Cdk) inhibitor 1B (commonly known p27(kip1) or p27) controls development in mice by suppressing promoting death. p27-deficient (p27(-/-)) mice, postnatal assembly was accelerated,...
Ceramide transfer protein (CERT) functions in the of ceramide from endoplasmic reticulum (ER) to Golgi. In this study, we show that CERT is an essential gene for mouse development and embryonic survival and, quite strikingly, critical mitochondrial integrity. mutant embryos accumulate ER but also mislocalize mitochondria, compromising their function. Cells abnormal dilation degenerating mitochondria. These subcellular changes manifest as heart defects cause severely compromised cardiac...
Both BTG1 and BTG2 are involved in cell-growth control. expression is regulated by p53, its inactivation embryonic stem cells leads to the disruption of DNA damage-induced G2/M cell-cycle arrest. In order investigate mechanism underlying Btg-mediated functions, we looked for possible functional partners Btg1 Btg2. Using yeast two-hybrid screening, protein-binding assays, transient transfection assays HeLa cells, demonstrated physicalin vitro vivo interaction both Btg2 with mouse protein...
We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)–expressing subventricular zone (SVZ) show no significant difference density and proliferation between Cdk2−/− wild-type mice at perinatal ages are reduced only adult mice. Adult SVZ culture display decreased self-renewal capacity enhanced differentiation. Compensatory mechanisms cells, which persist until day 15, involve increased...
The CCR4-associated protein CAF1 has been demonstrated to play several roles in the control of transcription and mRNA decay. To gain further insight into its physiological function, we generated CAF1-deficient mice. They are viable, healthy, normal appearance; however, mCAF1(-/-) male mice sterile. crossing mCAF1(+/-) gave a Mendelian ratio mCAF1(+/+), mCAF1(+/-), pups, indicating that haploid mCAF1-deficient germ cells differentiate normally. onset defect occurs during first wave...
Abstract Background: Several recent reports have connected protein methylation with differentiation. Furthermore, the BTG/TOB proteins also been implicated in such control. BTG1 and 2 shown to interact PRMT1 (predominant cellular arginine N‐methyltransferase of type I). Results: First, we studied interaction between family. We show that boxC, a sequence present only BTG2, is essential for this association. Using boxC peptide, investigated importance PRMT1/BTG association during I reactions....
It was believed that Cdk2-cyclin E complexes are essential to drive cells through the G1-S phase transition. However, it discovered recently mitotic kinase Cdk1 (Cdc2a) compensates for loss of Cdk2. In present study, we tested whether Cdk2 can compensate Cdk1. We generated a knockin mouse in which cDNA knocked into locus (Cdk1Cdk2KI). Substitution both copies by led early embryonic lethality, even though expressed from locus. addition, Cdk2-/- Cdk1+/Cdk2KI mice one copy and were gene deleted...
Abstract We generated a transgenic mouse strain (LSL‐TβRI CA ) containing latent constitutively active TGFβ type I receptor (TβRI/ALK5) by using knock‐in strategy into the X chromosome‐linked hypoxanthine phosphoribosyl‐transferase ( Hprt locus. Transgene expression, under control of ubiquitous CAG (human cytomegalovirus enhancer and chicken β‐actin) promoter, is repressed floxed transcriptional “Stop” (LSL, Lox‐Stop‐Lox). In presence cre‐recombinase, excised to allow TβRI transgene...
Cdk2 was once believed to play an essential role in cell cycle progression, but cdk2-/- mice have minimal phenotypic abnormalities. In this study, we examined the of cdk2 hepatocyte proliferation, centrosome duplication, and survival. Cdk2-/- hepatocytes underwent mitosis had normal content after mitogen stimulation. Unlike wild-type cells, liver cells failed undergo overduplication response ectopic cyclin D1 expression. After stimulation culture or partial hepatectomy vivo, demonstrated...
Progression through the mammalian cell cycle is associated with activity of four cyclin dependent kinases (Cdc2/Cdk1, Cdk2, Cdk4, and Cdk6). Knockout mouse models have provided insight into interplay these Cdks. Most do not exhibit major defects revealing redundancies, suggesting that a single Cdk might be sufficient to drive cycle, similar as in yeast. Recent work on Cdk2/Cdk4 double knockouts has indicated two Cdks are required phosphorylate Rb during late embryogenesis. The lack...
The G(1)/S-phase transition is a well-toned switch in the mammalian cell cycle. Cdk2, Cdk4, and rate-limiting tumor suppressor retinoblastoma protein (Rb) have been studied separate animal models, but interactions between kinases Rb vivo yet to be investigated. To further dissect regulation of G(1) S-phase progression, we generated Cdk2(-/-)Cdk4(-/-)Rb(-/-) (TKO) mutant mice. TKO mice died at midgestation with major defects circulatory systems displayed combined phenotypes Rb(-/-)...
The loss of p53 induces spontaneous tumors in mice, and mutations are found approximately 50% human tumors. These generally caused by a number events, including genomic instability, checkpoint defects, mitotic deregulation transcriptional targets, impaired apoptosis, G1 or combination these effects. In order to determine the role proteins involved control tumorigenesis, we focused on Cdk2 Cdk4, two cyclin-dependent kinases that association with cyclin E D promote G1/S phase transition. We...
It has long been believed that Cdk2 and its activator cyclin E play essential roles in the progression of mitotic cell cycle. However, recent studies using knockout mouse models revealed neither nor are vivo. The purpose this Perspective is to compare both mice discuss potential mechanisms driving cycle absence or E. Particular emphasis placed on possible non-catalytic E, expression activity second binding partner Cdk2, A, as well degradation inhibitor p27Kip1 Cdk2.
AbstractCell cycle regulation is essential for proper homeostasis of hematopoietic cells. Cdk2 a major regulator S phase entry, activated by mitogenic cytokines, and has been suggested to be involved in antigen-induced apoptosis T lymphocytes. The role cells vivo not yet addressed. To determine whether plays these cells, we performed multiple analyses bone marrow thymocytes, splenocytes from knockout mice. We found that required induce lymphocytes, result differs previous pharmacological...
AbstractGranule neurons of the dentate gyrus (DG) hippocampus undergo continuous renewal throughout life. Among cell-cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator S-phase entry. We used Cdk2-deficient mice to decipher requirement Cdk2 for generation new in adult hippocampus. The quantification cell cycle markers first revealed that lack activity does not influence spontaneous or seizure-induced proliferation neural progenitor cells (NPC) DG. Using...