scholarly journals A History of Cancer Research: Tumor Suppressor Genes

2020 ◽  
Vol 12 (2) ◽  
pp. a035907 ◽  
Author(s):  
Joseph Lipsick
Keyword(s):  
Cancer Research ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
History Of ◽  
History Of Cancer

No Reversal of Demethylation after Azacitidine Treatment in Concordance with Poor Clinical Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4629-4629
Author(s):  
Huong Thi Thanh Tran ◽  
Hee Nam Kim ◽  
JaeSook Ahn ◽  
Il-Kwon Lee ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Clinical Response ◽  
Methylation Level ◽  
Tumor Suppressor Genes ◽  
Gene Mutations ◽  
Molecular Monitoring ◽  
Suppressor Genes ◽  
Promoter Dna Methylation ◽  
History Of ◽  
Promoter Dna

Abstract The epigenetic gene silencing associated with promoter DNA methylation is as powerful as gene mutations in functionally inactivating tumor suppressor genes. Thus, a non-intensive treatment may be changed the natural history of MDS for the first time by the demethylating agent, 5-aza-deoxycytidine (Decitabine) with silenced gene expression by reversal of p15 hypermethylation and protein expression in the bone marrow in MDS. The MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification) ME-001B probemix (MRC-Holland) containing 25 tumor suppressor genes has been used to detect the methylation level in the peripheral blood samples of 29 MDS before azacitidine (Vidaza) and only 6 MDS after 3–5 courses of therapy. Patients that hypermethylated at least 1 gene were 7 of 29, either the common hypermethylating genes as p15, ESR1 or the previously known FHIT in MDS also have occurred. Only two patients except one patient related to either methylation level-reducing gene or removal methylated gene (putative demethylation reversal) have in concordance with clinical response in hematological evidence. Interestingly, three other patients were high methylation level persistently or additional methylated gene after treatment (putative demethylation no reversal or more severe), two patients of these are correspond with no clinical response and one is propensity to progressing leukemia. With IGSF4 gene hypermethylation, to the best of our knowledge, there was no report in MDS. Our results suggest that methylation level possibly contributes to the dignosistic, prognosistic and a molecular monitoring marker after treatment of Azacitidine.

Drosophila in cancer research: the first fifty tumor suppressor genes

1994 ◽  
Vol 1994 (Supplement 18) ◽  
pp. 19-33 ◽  
Author(s):  
K. L. Watson ◽  
R. W. Justice ◽  
P. J. Bryant
Keyword(s):  
Cancer Research ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes

scholarly journals TMOD-18. TARGETING THE PI3K/AKT PATHWAY IN MYCN AMPLIFIED HIGH GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii231-ii232
Author(s):  
Katharine Halligan ◽  
Ann-Catherine Stanton ◽  
Matthew Halbert ◽  
Brian Golbourn ◽  
Stephen Mack ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Suppressor ◽  
Mouse Model ◽  
Protein Expression ◽  
Neural Stem Cells ◽  
Tumor Suppressor Genes ◽  
Akt Pathway ◽  
High Grade ◽  
Suppressor Genes ◽  
High Grade Gliomas

Abstract Pediatric glioblastoma (pGBM) are incurable brain tumors with overall poor prognosis and response to treatments due to molecular and epigenetic heterogeneity. In particular, the MYCN subtype of pGBM are a highly aggressive form of GBM with a dismal median survival of only 14 months. Furthermore, this subtype is enriched with loss of the tumor suppressor genes TP53 and PTEN, leading to aberrantly active PI3K-AKT signaling pathway and DNA-checkpoint abnormalities. Here, we report the generation of a novel syngeneic mouse model that recapitulates the features of the MYCN subtype of pGBM. We isolated Sox2-Cre neural stem cells from C57BL/6 mice and transduced inverted retroviral-cassettes of the murine Mycn oncogene simultaneously with shRNA targeting tumor suppressor genes p53 and Pten. Retroviral-cassettes are flanked by tandem LoxP sites arranged so that Cre recombinase expression inverts the cassettes in frame allowing for MYCN protein expression and loss of the P53/PTEN proteins. Transgene activation is accompanied with selectable cell surface markers and fluorescent tags enabling for fluorescent activated cell sorting (FACS) of the desired cell populations. Neural stem cells with MYCN protein expression and concurrent silencing of P53 and PTEN protein (NPP cells) result in significantly increased proliferation and activation of PI3K-AKT pathway as compared to control neural stem cells and have. Injection of NPP cells into the forebrain of immune competent C57BL/6 mice result in the formation of invasive high-grade gliomas with a lethal phenotype at ~50 days post injection. Using several next generation brain penetrant small molecule inhibitors of the PI3K-AKT pathway, we show inhibition of tumorigenesis in vitro. Moreover, we have identified several novel mechanisms of PI3KAKT treatment resistance and are currently identifying therapies that may overcome this resistance through RNA seq analysis. In summary, well defined genetic drivers of GBM can lead to informed mouse model generation to test promising therapies.

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