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Poster Discussion 2 - Biology. Genome Transcriptome Proteome Metastasome. Genome. 39267: HDAC inhibitor/multidrug resistant cell lines PCI-24781 induces acetylation, inhibits growth, enhances chemosensitivity 39309: EXT /osteochondromas

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Poster Discussion 2 - Biology

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Poster discussion 2 biology l.jpg

Poster Discussion 2 - Biology

Genome

Transcriptome

Proteome

Metastasome


Genome l.jpg

Genome

  • 39267: HDAC inhibitor/multidrug resistant cell lines

    • PCI-24781 induces acetylation, inhibits growth, enhances chemosensitivity

  • 39309: EXT/osteochondromas

    • Biallelic inactivation of either EXT1 or EXT2 is less than expected for classic tumor suppressor model

  • 39356: DNA demethylation/synovial sarc

    • VPA and Zebularine (Zeb) are synergistic for suppression of growth of synovial sarcoma SYO-1 cells


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Genome

  • 39393: CNV (SNP)/osteosarcoma

    • Recurrent amplification: 1p36, 12q13-15, 17p11.2, 20p12

    • Recurrent deletion: 1q31, 6q16, 8q24.13, 10q23, 17p13

    • New targets to look for contribution to tumorigenesis

  • 39448*: Sleeping Beauty/osteosarcoma - forward genetic screen for new genomic loci


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Osteosarcoma Development and Metastasis Gene Discovery

B Moriartity and D Largaespada

Osteoblast precursor (Osx)-Cre

recombinase

p53R270H/+

T2/onc concatomer

Conditional sleeping beauty

osteosarcoma

Non-directed

Screen for

New Pathways

New gene

New loci that when interrupted by transposon (common insertion sites CIS) activates oncogene or inactivates tumor suppressor to contribute to osteosarcoma formation or metastasis.


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Transcriptome

  • 39218: DAXX mRNA/CASP8/p38 MAPK/sarcoma

    • 82 primary sarcomas, SW1353 chondrosarcoma line

    • FAS-mediated apoptosis via FADD/CASP8 or DAXX/ASK1

    • EGF-related association between CASP8 and DAXX may involve p38 MAPK pathway

  • 39338: GGAA/EWS-FLI regulation

    • NR0B1 (high in ES) promoter with ggaa repeats

    • Transcription by EWS/FLI requires dual binding of FLI

  • 39473: miRNA profiles/imatinib-treated GIST

    • GIST cell lines treated with imatinib

    • 10x upregulation of 23 microRNA

    • Check out a number of them from chromosome 14q32.31

  • 39354*: miRNA profiles/liposarcoma


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Identification of differentially expressed microRNAs in liposarcoma subtypes

Caroline Gits et al

12 liposarcomas

14 well-differenttiated

17 de-differentiated

9 myxoid

5 round cell

4 pleiomorphic

Lipomas, fat - 7/10

microRNAs

Hierarchal clustering

Differential

Expression

miRNAs

Myxoid

Round cell

De-differentiated

Discriminatory miRNAs

unsupervised - 585

supervised - 62

Which ones? - talk with Caroline


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Cell Biology

  • 38426: PRP-1/chondrosarcoma

    • PRP-1 isolated from neurosecretory cells of the hypothalamus; associated with myc expression leading to antiproliferation

    • Specific therapeutic window

  • 39388: Anti-CD99 antibody/Ewings

    • CD99 membrane glycocylated protein that when stimulated leads to reactivation of p53 pathway

    • Effective in sarcomas that have intact TP53


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Metastasome

  • 39270: expression profiles/osteosarcoma

    • 63 primary osteosarcoma patients (+/- mets)

    • Patterns predictive of metastatic tumors

    • RhoA pathway may be best discriminator

  • 39312: EMMPRIN/osteosarcoma


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Emmprin expression is associated with metastatic phenotype in osteosarcoma

H Han et al.

EMMPRIN - Extracellular matrix metalloproteinase inducer

- 16 osteosarcoma cell lines versus normal osteoblast - RT-PCR

- IHC in 52 prechemotherapy patient biopsies

- siRNA knockdown of Emmprin in HOS and SaOS-2

- Gelatin zymography, VEGF ELISA, Matrigel invasion assay (HOS)

- Co-culture SaOS-2 with osteoblast (hFOB) and fibroblast (MRC-5)

EMMPRIN

Knock down EMMPRIN?

MMPsVEGF

(Cancer cells and stroma)


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Emmprin expression is associated with metastatic phenotype in osteosarcoma

H Han et al.

EMMPRIN - Extracellular matrix metalloproteinase inducer

- 16 osteosarcoma cell lines versus normal osteoblast - RT-PCR

- IHC in 52 prechemotherapy patient biopsies

- siRNA knockdown of Emmprin in HOS and SaOS-2

- Gelatin zymography, VEGF ELISA, Matrigel invasion assay (HOS)

- Co-culture SaOS-2 with osteoblast (hFOB) and fibroblast (MRC-5)

EMMPRIN

Knock down EMMPRIN?

Make things better!

MMPsVEGF

(Cancer cells and stroma)


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