scholarly journals The ARF protein in tumor suppression: lessons from mouse models and human tumors

2004 ◽  
Vol 6 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Ignacio Palmero Rodríguez
Keyword(s):  
Mouse Models ◽  
Tumor Suppression ◽  
Human Tumors ◽  
Arf Protein

scholarly journals Integrative genomic analysis of mouse and human hepatocellular carcinoma

2018 ◽  
Vol 115 (42) ◽  
pp. E9879-E9888 ◽  
Author(s):  
Michelle Dow ◽  
Rachel M. Pyke ◽  
Brian Y. Tsui ◽  
Ludmil B. Alexandrov ◽  
Hayato Nakagawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mouse Models ◽  
Cancer Genomics ◽  
Genomic Analysis ◽  
Human Tumors ◽  
Low Grade ◽  
Mhc I ◽  
Molecular Features ◽  
Frequent Mutations

Cancer genomics has enabled the exhaustive molecular characterization of tumors and exposed hepatocellular carcinoma (HCC) as among the most complex cancers. This complexity is paralleled by dozens of mouse models that generate histologically similar tumors but have not been systematically validated at the molecular level. Accurate models of the molecular pathogenesis of HCC are essential for biomedical progress; therefore we compared genomic and transcriptomic profiles of four separate mouse models [MUP transgenic, TAK1-knockout, carcinogen-driven diethylnitrosamine (DEN), and Stelic Animal Model (STAM)] with those of 987 HCC patients with distinct etiologies. These four models differed substantially in their mutational load, mutational signatures, affected genes and pathways, and transcriptomes. STAM tumors were most molecularly similar to human HCC, with frequent mutations in Ctnnb1, similar pathway alterations, and high transcriptomic similarity to high-grade, proliferative human tumors with poor prognosis. In contrast, TAK1 tumors better reflected the mutational signature of human HCC and were transcriptionally similar to low-grade human tumors. DEN tumors were least similar to human disease and almost universally carried the Braf V637E mutation, which is rarely found in human HCC. Immune analysis revealed that strain-specific MHC-I genotype can influence the molecular makeup of murine tumors. Thus, different mouse models of HCC recapitulate distinct aspects of HCC biology, and their use should be adapted to specific questions based on the molecular features provided here.

Pharmacologic Inhibitor of DNA-PK, M3814, Potentiates Radiotherapy and Regresses Human Tumors in Mouse Models

2020 ◽  
Vol 19 (5) ◽  
pp. 1091-1101 ◽  
Author(s):  
Frank T. Zenke ◽  
Astrid Zimmermann ◽  
Christian Sirrenberg ◽  
Heike Dahmen ◽  
Vladimir Kirkin ◽  
...  
Keyword(s):  
Mouse Models ◽  
Human Tumors

scholarly journals Neuroendocrine Lung Cancer Mouse Models: An Overview

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 14
Author(s):  
Corina Lorz ◽  
Marta Oteo ◽  
Mirentxu Santos
Keyword(s):  
Lung Cancer ◽  
Molecular Imaging ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Somatostatin Receptors ◽  
Unmet Need ◽  
Human Tumors ◽  
Low Grade ◽  
Cell Lung Carcinoma

Neuroendocrine lung tumors comprise a range of malignancies that extend from benign tumorlets to the most prevalent and aggressive Small Cell Lung Carcinoma (SCLC). They also include low-grade Typical Carcinoids (TC), intermediate-grade Atypical Carcinoids (AC) and high-grade Large Cell Neuroendocrine Carcinoma (LCNEC). Optimal treatment options have not been adequately established: surgical resection when possible is the choice for AC and TC, and for SCLC chemotherapy and very recently, immune checkpoint inhibitors. Some mouse models have been generated based on the molecular alterations identified in genomic analyses of human tumors. With the exception of SCLC, there is a limited availability of (preclinical) models making their development an unmet need for the understanding of the molecular mechanisms underlying these diseases. For SCLC, these models are crucial for translational research and novel drug testing, given the paucity of human material from surgery. The lack of early detection systems for lung cancer point them out as suitable frameworks for the identification of biomarkers at the initial stages of tumor development and for testing molecular imaging methods based on somatostatin receptors. Here, we review the relevant models reported to date, their impact on the understanding of the biology of the tumor subtypes and their relationships, as well as the effect of the analyses of the genetic landscape of the human tumors and molecular imaging tools in their development.

Reversible Tumor Suppression By Ikzf1/Ikaros in Mouse Models of BCR-ABL1+ B-ALL

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 288-288
Author(s):  
Matthew T Witkowski ◽  
Yifang Hu ◽  
Luisa Cimmino ◽  
Mark D McKenzie ◽  
Grace J Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Mouse Models ◽  
Tumor Suppression ◽  
Genetic Interaction ◽  
Lymphoblastic Leukemia ◽  
Differentially Expressed ◽  
Sustained Remission ◽  
Loss Of Function ◽  
Regulated Gene Expression

Abstract Background: Loss-of-function mutations in the transcription factor IKZF1 (IKAROS) correlate with poor prognosis in B-progenitor acute lymphoblastic leukemia (B-ALL), and are particularly prevalent in the high-risk BCR-ABL1+ and BCR-ABL1-like disease subtypes. While recent studies using mouse models of Ikaros-deficient B-ALL have uncovered Ikaros-regulated genes, the mechanisms by which IKAROS loss promotes leukemogenesis and confers treatment resistance remain unclear. Results: We have generated a novel transgenic mouse model that allows tet-regulated, shRNA-mediated Ikaros knockdown or restoration in normal lymphocytes and leukemias in vivo. Ikaros knockdown significantly decreases disease latency in mouse models of B-ALL driven by transgenic or retroviral expression of the BCR-ABL1 fusion oncogene, recapitulating a common genetic interaction in high-risk pediatric B-ALL. Remarkably, we find that restoring endogenous Ikaros expression in established BCR-ABL1+ ALL causes rapid disease regression and sustained remission despite ongoing expression of BCR-ABL1, indicating that disabled Ikaros remains a critical disease driver in this context. Using integrated in vivo RNA-seq analysis we have identified a novel set of genes that are (1) differentially expressed in Ikaros-low versus Ikaros-wildtype leukemias and (2) concordantly differentially expressed upon acute Ikaros restoration in established Ikaros-low leukemias. We are now performing in vitro and in vivo loss-of-function genetic screens to interrogate these high confidence Ikaros-regulated genes, focusing on potential roles for Ikaros-activated genes in tumor suppression and Ikaros-repressed genes in promoting BCR-ABL1+ ALL self-renewal. Conclusions: Our results demonstrate that B-ALL driven by expression of BCR-ABL1 and Ikaros loss remains dependent on ongoing Ikaros suppression, suggesting that re-engaging or inhibiting critical components of the Ikaros-regulated gene expression program may provide new therapeutic avenues in this high-risk B-ALL subtype. Disclosures No relevant conflicts of interest to declare.

Studies of p53 Tumor Suppression Activity in Mouse Models

2002 ◽  
Vol 3 (4) ◽  
pp. 265-283 ◽  
Author(s):  
Dionisio Martin-Zanca
Keyword(s):  
Mouse Models ◽  
Tumor Suppression

scholarly journals Mouse models in tumor suppression

Oncogene ◽  
1998 ◽  
Vol 17 (25) ◽  
pp. 3385-3400 ◽  
Author(s):  
Nader Ghebranious ◽  
Lawrence A Donehower
Keyword(s):  
Mouse Models ◽  
Tumor Suppression
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