Results: 5

1.
Figure 1

Figure 1. From: Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification.

Different kinetics of retinoblastoma emergence in Rb/p107 versus Rb/p130 DKOs. Kaplan–Meier curve showing time to first observation of externally visible retinoblastoma. Inset: retinoblastoma visible in the anterior chamber of an Rb/p130 DKO mouse at 4 months of age.

David MacPherson, et al. EMBO J. 2007 February 7;26(3):784-794.
2.
Figure 3

Figure 3. From: Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification.

Proliferation and apoptosis in Rb/p130 DKOs at PND12. (A) BrdU incorporation in retinas from wild-type, Rblox/lox αCre (Rb KO) and Rb/p130 DKO animals. Ganglion (g), inner nuclear (i) and outer nuclear (o) layers are indicated. Scale bar=200 μm (low magnification) and 40 μm (high magnification). (B) Caspase3 immunostaining in retinas from wild-type, Rblox/loxαCre and Rb/p130 DKO animals. Scale bar=40 μm. (C) Quantification of Brdu and Caspase3 staining. Quantification was performed on horizontal sections at the optic nerve level in a region from the peripheral tip of the retina extending 1000 μm toward central retina. WT N=3; Rb KO N=4, Rb/p130 DKO N=8. Error bars represent standard deviation. P-values (Student's t-test) are shown.

David MacPherson, et al. EMBO J. 2007 February 7;26(3):784-794.
3.
Figure 4

Figure 4. From: Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification.

Tumor progression in murine Rb/p130 DKO retinoblastoma. Histology and immunostaining of late retinoblastoma and metastases in Rb/p130 DKOs from 5 to 7 months of age. Scale bar=200 μm for low power and 60 μm for high power (inset) images. (A) Bilateral retinoblastoma in a 5-month-old mouse (left). Fundus photograph of late-stage retinoblastoma that fills the vitreous at 5 months (right). (B) H+E stain of late retinoblastoma, with blood and tumor in the anterior chamber (AC) and invasion of the optic nerve (inset). (C) H+E stain of lymph node metastasis, adjacent to the salivary gland. Tumor rosettes are apparent on the high-magnification image (inset). (D) H+E stain of brain with retinoblastoma invading into brain parenchyma (inset). (E) Syntaxin immunohistochemistry of lymph node metastasis. (F) Calretinin immunohistochemistry of lymph node metastasis. (G) Calbindin immunohistochemistry of lymph node metastasis. (H) Glial fibrillary acidic protein (GFAP) immunohistochemistry of lymph node metastasis.

David MacPherson, et al. EMBO J. 2007 February 7;26(3):784-794.
4.
Figure 2

Figure 2. From: Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification.

Rb/p130 DKO tumors emerge from the extreme periphery of retina. Early retinoblastomas in Rb/p130 DKOs. (A–F) Histology and immunostaining of PND21 retinas from wild-type (left panel) and Rb/p130 DKO (middle, right panels) animals. The upper inset in the middle panel shows details of Rb/p130 DKO retina adjacent to tumor. The panel in the right shows details from Rb/p130 DKO early tumor. Scale bars in the left and middle low-power panels=200 μm, high-magnification insets and right panels, 40 μm. (A) Hematoxylin and eosin (H+E) stain with normal eye structures labeled. Distinct regional phenotypes and early retinoblastoma in the Rb/p130 DKO are noted. (B) BrdU labeling of proliferating cells. (C) Syntaxin immunostaining. Note the depletion of amacrine cells adjacent to tumor (inset, middle panel) and the positive staining of early retinoblastoma (right). (D) Calretinin immunostaining labeling an amacrine and ganglion subset. (E) Calbindin immunostaining. Arrows indicate calbindin-positive horizontal cells. (F) GLAST immunostaining labeling Müller glia. (G) Fundus photograph of a p130−/− control mouse at 6 weeks of age. The ciliary body, peripheral to the neural retina, is indicated (white arrow). (H) Fundus photograph of Rb/p130 DKO mouse at 6 weeks of age. Peripheral retina is shown and black arrows point to early retinoblastoma at the extreme periphery. Retinal pigment epithelial changes due to retinal degeneration are present. The ciliary body, adjacent to the neural retina, is indicated (white arrow).

David MacPherson, et al. EMBO J. 2007 February 7;26(3):784-794.
5.
Figure 5

Figure 5. From: Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification.

N-Myc amplification and overexpression in retinoblastomas. (A) ROMA moving median plot showing signal intensity plotted for the whole genome comparing tail (Cy3 labeled) and lymph node metastasis (Cy5 labeled) DNA from tumor 9806. Specific changes from this tumor detailed in Table I include gains of chromosomes 1 and 12, as well as two focal chromosome 12 amplicons. (B) Southern analysis of DNA from lymph node Rb/p130 DKO retinoblastoma metastases or normal tail DNA. DNA was digested with EcoR1 and probed with an N-myc cDNA fragment. Following N-myc detection, blot was rehybridized to an LR8 probe to control for loading. Fold amplification as assessed by phosphorimager analysis of the same blot is shown. Samples with amplification are highlighted in bold. (C) Southern analysis of Rb/p107 DKO primary (pri) or metastatic (met) retinoblastomas. Hybridization with LR8 probe was used as a loading control. Samples with amplification are highlighted in bold. (D) Northern analysis of N-myc expression in retinoblastomas. Samples with N-myc genomic amplification are highlighted in bold. N-myc levels were extremely high in Rb/p107 DKO tumor J643. A lower exposure of the right side of this blot containing J643 is shown (right). Quantification of N-myc relative to ARPP P0 loading control shows highest expression in N-myc-amplified samples. (E) A core amplified region of 136 kb in murine retinoblastomas. The 12qA1.1 amplified regions of three murine retinoblastomas (9806, 4836 and drb13) are shown. Shaded area (136 kb in size; 12 937 244–13 073 187 UCSC May/2004 build) indicates the genomic area that is amplified in all three tumors. N-myc is the only RefSeq gene inside the core amplicon.

David MacPherson, et al. EMBO J. 2007 February 7;26(3):784-794.

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