Expression of p53 and Mdm2 in Human Retinoblastoma

Saxena, Pravin

doi:10.4172/2155-9570.1000236

Cited by 3 publications

(5 citation statements)

References 21 publications

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“…The data on HDM2 overexpression in RB tumors from different studies are inconsistent. 13 , 28 , 29 Hence, we attempted to study HDM2 expression in a clinically well-defined cohort ( Tables S1 A and S1B) by gene and protein expression, to rationalize its potential for targeted therapy in RB. The gene expression analysis of RB tumors revealed that HDM2 was significantly overexpressed in RB cells compared to normal cells ( Figures 1 A and 1B).…”

Section: Resultsmentioning

confidence: 99%

Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma

Kalmodia

Parameswaran

Ganapathy

et al. 2017

Molecular Therapy - Nucleic Acids

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Inhibition of the interaction between p53 and HDM2 is an effective therapeutic strategy in cancers that harbor a wild-type p53 protein such as retinoblastoma (RB). Nanoparticle-based delivery of therapeutic molecules has been shown to be advantageous in localized delivery, including to the eye, by overcoming ocular barriers. In this study, we utilized biocompatible gold nanoparticles (GNPs) to deliver anti-HDM2 peptide to RB cells. Characterization studies suggested that GNP-HDM2 was stable in biologically relevant solvents and had optimal cellular internalization capability, the primary requirement of any therapeutic molecule. GNP-HDM2 treatment in RB cells in vitro suggested that they function by arresting RB cells at the G2M phase of the cell cycle and initiating apoptosis. Analysis of molecular changes in GNP-HDM2-treated cells by qRT-PCR and western blotting revealed that the p53 protein was upregulated; however, transactivation of its downstream targets was minimal, except for the PUMA-BCl2 and Bax axis. Global gene expression and in silico bioinformatic analysis of GNP-HDM2-treated cells suggested that upregulation of p53 might presumptively mediate apoptosis through the induction of p53-inducible miRNAs.

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Section: Resultsmentioning

confidence: 99%

Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma

Kalmodia

Parameswaran

Ganapathy

et al. 2017

Molecular Therapy - Nucleic Acids

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“…[ 6 ] Incidence of HRF is reported to be higher in India and other developing countries. [ 8 9 10 11 12 16 ] Possible explanation being, patients coming to seek treatment at a more advanced stage of the disease, or probably a different biological behavior of the malignancy in different geographic locations. [ 9 ] In a study by Chantada et al .,[ 11 ] poor parental education, socioeconomic factors, and access to health care correlated significantly with late consultation, delayed diagnosis, and increased risk of extraocular disease.…”

Section: Discussionmentioning

confidence: 99%

“…p53 expression was observed in 21 (35%) of the tumors, however, there was no correlation in p53 and HRF statistically. [ 16 ]…”

Section: Discussionmentioning

confidence: 99%

High-risk histomorphological features in retinoblastoma and their association with p53 expression: An Indian experience

Rao

Sobti

Khurana

et al. 2014

Indian J Ophthalmol

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Introduction:Histopathological features in retinoblastoma are considered high-risk factors (HRF) for tumor progression and metastasis, thus their presence becomes an indication for adjuvant chemotherapy. Present study was undertaken to evaluate the incidence of HRF in retinoblastoma and to correlate them with p53 expression.Materials and Methods:This was a retrospective study where 17 diagnosed cases of retinoblastoma were included. Cases were re-evaluated for various histomorphological parameters. Immuno-histochemical analysis was done with p53 antibody by Streptavidin biotin method.Results:The patients were in the age range of 1.5-50 years. Common histological features included necrosis (70.5%), calcification (64.7%), and retinal detachment (58.8%). Incidence of various morphological parameters was anterior chamber seeding (47.2%), ciliary body involvement (29.4%), iris involvement (29.4%), choroid involvement (58.8%), scleral invasion (29.4%), extrascleral invasion (11.8%), and optic nerve infiltration (23.5%). p53 expression was present in four cases out of 13 cases (30.7%) and showed a significant association with choroid invasion (P = 0.02).Discussion:The presence of HRF should alert the physician for a possible metastasis, and such patients should be kept on regular follow-up to detect an early recurrence. p53 expression, a known poor prognostic indicator, showed significant association with choroid invasion, however, no association was seen with other HRF.Conclusion:Histopathological HRF have significant therapeutic and prognostic implications. The incidence of HRF is higher in developing countries as patients present with a more advanced stage of disease. p53 expression is significantly associated with choroid invasion out of all HRF.

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“… 13–15 Other tumour markers such as p53 have been found to correlate significantly with the HHRFs including massive choroidal invasion and positive surgical margin of the optic nerve. 16 …”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that increased expression of cell proliferation biomarkers such as Ki67 is associated with advanced tumour stage and poor clinical outcomes 13–15. Other tumour markers such as p53 have been found to correlate significantly with the HHRFs including massive choroidal invasion and positive surgical margin of the optic nerve 16…”

Section: Introductionmentioning

confidence: 99%

Expression of Ki67 as detected by MIB-1 and its association with histopathological high-risk factors among patients with retinoblastoma tumour: a cross-sectional study

2022

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ObjectivesThis study aims to investigate the expression of Ki67 in formalin-fixed paraffin-embedded tissue blocks from patients with a diagnosis of retinoblastoma tumour (RbT) as well as determining its association with histopathological high-risk factors (HHRFs).Methods and analysisRetrospectively, a total of 194 eyeball specimens from 163 children with RbT were reviewed at Muhimbili National Hospital between 2009 and 2013. Immunohistochemical expression of Ki67 using MIB-1 antibody (Abcam, batch ab93680, Cambridge, UK) was determined and correlated with the conventional HHRFs. The predictors of Ki67 expression were determined using binary logistic regression model in multivariate analysis. A two-tailed p<0.05 was considered statistically significant.ResultsMajority (67.5%) of the patients had leukocoria and extraocular disease was found in 20.9% of all the patients. High expression of Ki67 was present in 63.8% of the 80 eyeballs that were tested. Massive choroidal invasion (adjusted OR (AOR)=9.32, 95% CI=2.82 to 10.89), positive retrolaminar optic nerve invasion (AOR=3.01, 95% CI=4.43 to 9.11), positive surgical margin (AOR=7.10, 95% CI=1.63 to 11.40) and pT4 (AOR=7.49, 95% CI=0.12 to 0.89) were the potential HHRFs that were associated with Ki67 overexpression.ConclusionOverexpression of Ki67 may be of prognostic value for patients with RbT as it has been shown in the present study that high expression was common in tumours with massive choroidal invasion, positive retrolaminar optic nerve invasion, positive surgical margin and advanced tumour stage, which are the conventional HHRFs associated with prognosis of RbT.

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Expression of p53 and Mdm2 in Human Retinoblastoma

Cited by 3 publications

References 21 publications

Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma

Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma

High-risk histomorphological features in retinoblastoma and their association with p53 expression: An Indian experience

Expression of Ki67 as detected by MIB-1 and its association with histopathological high-risk factors among patients with retinoblastoma tumour: a cross-sectional study

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