Lack of RAD51 nuclear foci identifies PARPi‐sensitive PDX tumors

Slides:

Advertisements

Similar presentations

Effects of inhibiting inflammatory cell recruitment on fracture healing Treatment with CCR2 antagonist, INCB3344, led to impaired fracture healing compared.

Advertisements

Role of TNF in fracture healing in vivo Addition of rhTNF at the fracture site on days 0 and 1 led to augmented healing, indicated by increased % callus.

Loss of Hdac3 impairs Ar signaling in mouse prostate tissues and has no effect on apoptosis Loss of Hdac3 impairs Ar signaling in mouse prostate tissues.

DNA damage foci in irradiated cells.

HDAC3 regulates AKT phosphorylation

The HDAC3 inhibitor suppresses SPOP‐mutated prostate cancer cell growth The HDAC3 inhibitor suppresses SPOP‐mutated prostate cancer cell growth A22Rv1.

AβOs bind to and impact hypothalamic neurons Representative immunocytochemistry images of mature hypothalamic neurons in culture exposed to vehicle (Veh)

The gene encoding TP53INP1 is expressed in pancreatic endocrine cells A, B(A, B) Immunocytofluorescent staining of TP53INP1 (red) and insulin (green) in.

PbA‐specific CD4 T‐cell responses are maximal at day 6 post‐pRBC infection PbA‐specific CD4 T‐cell responses are maximal at day 6 post‐pRBC infection Proportion.

[68Ga]Pentixafor PET imaging of MM xenografts Real‐time PCR analysis of cxcr4 transcript expression levels in HeLa (negative control) and in MM cell lines.

AAV8‐hAAT‐FGF21 treatment improves liver fibrosis

Mitochondrial targeting of ceramide induces lethal mitophagy in HPV(+) cells Mitochondrial targeting of ceramide induces lethal mitophagy in HPV(+) cells.

BRD4 is associated with poor patient survival and constitutes a promising target for NRASMut melanoma BRD4 is associated with poor patient survival and.

Dual LGR5 and KI67 knock‐in PDOs enable separation of quiescent and cycling LGR5+ CRC cells Dual LGR5 and KI67 knock‐in PDOs enable separation of quiescent.

Metabolic profile of Tfe3 KO mice

Phenogenetic networks of genes linked to Alzheimer's and Parkinson's disease reveal concordant phenotypes Phenogenetic networks of genes linked to Alzheimer's.

Dynamics and variability of SMAD2 signaling in single cells

Stat3 promotes lung fibrosis and collagen synthesis independent of Smad3.A.Masson's trichrome stained sections of lung from gp130wt (wt), Smad3−/− (Smad3−/−),

TFE3 prevents diet‐induced obesity and metabolic syndrome

Selective biodistribution and receptor‐dependent uptake of T22‐GFP‐H6‐FdU in CXCR4+ cells in vivo Selective biodistribution and receptor‐dependent uptake.

JNK signaling mediates mammary tumor growth and metastasis to lungs

HSPC and T‐cell transduction

HPV‐E7/RB axis regulates ceramide‐dependent mitophagy via E2F5 activation HPV‐E7/RB axis regulates ceramide‐dependent mitophagy via E2F5 activation AUM‐SCC‐47.

SPP1 and TNC promote chemoresistance

Expression of PD‐1 on PBMC and malignant exudate T cells

Expression and occupancy of a set of transcription factors corresponding to the identified motifs at FAIRE peaks Expression and occupancy of a set of transcription.

Integrated protein co‐expression and differential expression across the ALS‐FTD disease continuum Integrated protein co‐expression and differential expression.

Identification of miR‐499 targets

T22‐GFP‐H6‐FdU prevents metastasis in the M5 patient‐derived model in a CXCR4‐dependent manner T22‐GFP‐H6‐FdU prevents metastasis in the M5 patient‐derived.

Mitochondrial ceramide is involved in HPV‐E7‐mediated lethal mitophagy

Combination of OTX‐015 and PD does not induce overt toxicity

Stat3C/C mice are more prone to Th17 differentiation. A

SPRY2 deficiency‐induced SRB1 mediates CRPC

PERK activator treatment protects neurite network

BETi potentiate the efficacy of MEKi in NRAS‐mutant melanoma

Nec‐1 inhibits the phosphorylation and aggregation of tau

Effects of in vivo Nutlin‐3 treatment on CSC content of Numb− and Numb+ tumors Effects of in vivo Nutlin‐3 treatment on CSC content of Numb− and Numb+

SPP1 and TNC are induced by chemotherapy via JNK signaling

TGF‐β1 treatment induces the chromatin binding of Smad2/3/4 in 4T1 cells TGF‐β1 treatment induces the chromatin binding of Smad2/3/4 in 4T1 cells A, BWestern.

IL‐23‐induced psoriasis‐like skin disease is ameliorated in IL‐23−/− mice IL‐23‐induced psoriasis‐like skin disease is ameliorated in IL‐23−/− mice ARepresentative.

Hccs downregulation induces apoptosome‐independent caspase‐9 activation in mitochondria.A–C.TUNEL assays on st30 embryos co‐injected with hccs‐MO and Apaf1‐MO.

Inhibition of NAMPT using the potent inhibitor FK866 sensitizes additional tumour cells to olaparib.A‐E.Sensitivity of the cell lines MDAMB468 (A), SUM149.

Impact of ONX 0914 on abundance and dissemination of monocytes/macrophages during CVB3 infection Impact of ONX 0914 on abundance and dissemination of monocytes/macrophages.

MET inhibition promotes p21 nuclear translocation

Enhancement of receptor endocytosis, as well as cellular apoptosis, may explain the cooperative anti‐tumor actions of 3×mAbs and osimertinib Enhancement.

GPR120 deficiency alters the expression of genes involved in glucose and lipid metabolism in BAT GPR120 deficiency alters the expression of genes involved.

Distinct collagen structures in the upper and lower neonatal dermis (related to Fig 1)‏ Distinct collagen structures in the upper and lower neonatal dermis.

Assessment of proliferation status of PDGFRα+ cells in developing mouse lungs Assessment of proliferation status of PDGFRα+ cells in developing mouse lungs.

The HDAC3 inhibitor suppresses PTEN‐deficient prostate cancer growth

The antitumor activity of olaparib in PDXs identifies a subset of PARPi‐sensitive tumors The antitumor activity of olaparib in PDXs identifies a subset.

Drp1 knockdown prevents mitophagy

XBP1s and RIDD of mRNA signals in GBM

Growth of TKI‐resistant EGFR delE746‐A750 PC‐9 NSCLC cells is associated with elevated cellular free fatty acid and expression of FASN, and is suppressed.

Effect of RK‐33 on radiation‐induced DNA damage AImmunofluorescence images showing 53BP1 and γH2AX foci in A549 cells after 2‐Gy radiation and A549 cells.

T22‐GFP‐H6‐FdU‐induced depletion of CXCR4‐overexpressing cancer cells in tumor tissue T22‐GFP‐H6‐FdU‐induced depletion of CXCR4‐overexpressing cancer cells.

Activation of Drp1 by E2F5‐Drp1 complex enhances HPV‐E7/ceramide‐mediated lethal mitophagy Activation of Drp1 by E2F5‐Drp1 complex enhances HPV‐E7/ceramide‐mediated.

UCN‐01 inhibits FoxO3 inactivation in human lung fibroblasts stimulated with growth factors UCN‐01 inhibits FoxO3 inactivation in human lung fibroblasts.

The MEK inhibitor CI‐1040 reverses thickening, fibrosis, and angiogenesis in the parietal peritoneum of Cav1−/− mice upon exposure to PD fluidWT or Cav1−/−

Therapeutic activity of gal‐encapsulated cytotoxic drugs on tumor xenografts Therapeutic activity of gal‐encapsulated cytotoxic drugs on tumor xenografts.

PKAN human neurons show altered oxidative status

Tissue‐specific differences in the levels of CoQ9, CoQ10, and DMQ9, and in the DMQ9/CoQ9 ratio after β‐RA treatment in Coq9R239X mice Tissue‐specific differences.

Effect of rare SVs on cardiac transcription in DCM

P2X4R blockade increases pro‐inflammatory gene expression after EAE

CNP520 treatment of male C57/BL6 mice for 8 weeks did not cause hair depigmentation CNP520 treatment of male C57/BL6 mice for 8 weeks did not cause hair.

Bevacizumab therapy leads to reduced vessel density and increased Ang‐2 expression Bevacizumab therapy leads to reduced vessel density and increased Ang‐2.

UCN‐01 inhibits human IPF lung fibroblast pathological phenotypes and attenuates lung fibrosis induced by bleomycin injury UCN‐01 inhibits human IPF lung.

Limiting neutrophilic inflammation during active phase (ZT13) reduces MI damage Limiting neutrophilic inflammation during active phase (ZT13) reduces MI.

Niacin suppresses pro‐inflammatory cytokine expression in macrophages in DSS‐induced colitis in mice Niacin suppresses pro‐inflammatory cytokine expression.

Socs1 KD tumors exhibit a more T-cell–inflamed phenotype and increased T-cell activation. Socs1 KD tumors exhibit a more T-cell–inflamed phenotype and.

Interaction of NHEJ and HR pathways in PCO cultures.

Presentation transcript:

Lack of RAD51 nuclear foci identifies PARPi‐sensitive PDX tumors Lack of RAD51 nuclear foci identifies PARPi‐sensitive PDX tumors APercentage of geminin‐positive, RAD51 nuclear foci‐containing cells detected by immunofluorescence in FFPE samples from PDX tumors treated with vehicle or PARPi (larger views and separate channels are shown in Appendix Fig S2). Error bars indicate SEM from independent tumors (n ≥ 2). PARPi response is shown in the summary underneath: white box: PD; black box: PR/CR. Immunofluorescence staining of RAD51 foci in PARPi‐ and vehicle‐treated PDX tumors is shown. Alterations in HRR‐related genes are also summarized: hBRCA1: BRCA1 promoter hypermethylation and lack of BRCA1 expression and BRCA1 nuclear foci formation.BRestoration of RAD51 foci formation in PARPi acquired‐resistant PDXs. Immunofluorescence staining of BRCA1 and RAD51 foci in PARPi‐treated tumors from STG201, PDX302, and the corresponding PARPi acquired‐resistant models (STG201OR and PDX302OR). Scale bars: 10 μm.CQuantification of geminin‐positive cells that exhibit γ‐H2AX nuclear foci following treatment with vehicle and olaparib. Paired t‐test in PARPi‐sensitive (CR/PR) versus PARPi‐resistant (PD) PDXs. Marta Castroviejo‐Bermejo et al. EMBO Mol Med. 2018;emmm.201809172 © as stated in the article, figure or figure legend