High-Level Amplified Proficient Retinoblastoma Tumors Retain Distinct Molecular Signatures.

Purpose: Retinoblastomas are malignant eye tumors diagnosed in young children. Most retinoblastomas are genetically characterized by biallelic inactivation of the gene. However, 1.

At What Age Could Screening for Familial Retinoblastoma Be Discontinued? A Systematic Review.

The aim of this systematic review is to assess the latest age at diagnosis for detection of familial retinoblastoma in order to evaluate at what age screening of at-risk children could be discontinued. Extended screening beyond this age would result in unnecessary patient burden and costs. However, discontinuing screening prematurely would have the adverse effect of missing tumors.

Benign Tumors in Long-Term Survivors of Retinoblastoma.

Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.

Subsequent Malignant Neoplasms in Retinoblastoma Survivors.

Retinoblastoma (Rb) is a pediatric malignant eye tumor. Subsequent malignant neoplasms (SMNs) and trilateral Rb (TRb) are the leading cause of death in heritable Rb patients in developed countries. The high rate of SMNs in heritable Rb patients is attributed to the presence of a mutation in the tumor suppressor gene.

Recommendations for Long-Term Follow-up of Adults with Heritable Retinoblastoma.

Purpose: To generate recommendations for long-term follow-up of adult survivors of heritable retinoblastoma.

Design: We convened a meeting of providers from retinoblastoma centers around the world to review the state of the science and to evaluate the published evidence.

Participants: Retinoblastoma is a rare childhood cancer of the retina.

Optical coherence tomography (OCT) to image active and inactive retinoblastomas as well as retinomas.

Purpose: To illustrate Optical Coherence Tomography (OCT) images of active and inactive retinoblastoma (Rb) tumours.

Methods: Current observational study included patients diagnosed with retinoblastoma and retinoma who were presented at Amsterdam UMC and Jules-Gonin Eye Hospital, between November 2010 and October 2017. Patients aged between 0 and 4 years were imaged under general anaesthesia with handheld OCT in supine position.

Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.

Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming.

Feasibility of RetinoQuest: e-health application to facilitate and improve additional care for retinoblastoma survivors.

Purpose: The current study aimed to evaluate the feasibility of RetinoQuest in clinical practice, from survivors and healthcare professionals' (HCPs) point of view.

Methods: RetinoQuest is a touch screen computer program to monitor health-related quality of life (HRQoL) of retinoblastoma survivors via patient-reported outcome measures (PROMs) targeting children (4-10 years) as evaluated by their parents (proxy measures), adolescents (11-18 years), and adults. Feasibility was evaluated by the actual time taken to complete the PROMs, acceptability of the time as perceived by the users, the content of PROMs in RetinoQuest, and overall satisfaction with RetinoQuest.

Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years.

Background/aims: Survivors of retinoblastoma carry a lifetime risk of secondary malignancies. It is well established that external beam radiation increases this risk; however, the risk with ophthalmic artery chemosurgery (OAC) remains unknown. We report on 10 years of experience with OAC and the rate of second primary malignancy (SPM) development.

Ophthalmic artery chemosurgery for eyes with advanced retinoblastoma.

Background: Surgical removal of one or both eyes has been the most common way to treat children with retinoblastoma worldwide for more than 100 years. Ophthalmic artery chemosurgery (OAC) was introduced 10 years ago and it has been used as an alternative to enucleation for eyes with advanced retinoblastoma. The purpose of this report is to analyze our 9-year experience treating advanced retinoblastoma eyes with OAC.

OCULAR PHARMACOLOGY OF CHEMOTHERAPY FOR RETINOBLASTOMA.

Purpose: To review preclinical and clinical pharmacokinetic studies of the three most important chemotherapy drugs used for intraocular retinoblastoma and the contribution of the reported results to optimize treatment.

Methods: Systemic review of pharmacokinetic studies identified by a literature search at Pubmed using the keywords carboplatin, melphalan, topotecan, intravitreal, ophthalmic artery chemosurgery, pharmacokinetics, and retinoblastoma.

Results: A total of 21 studies were reviewed for assessing the preclinical and clinical pharmacokinetics of carboplatin, topotecan, and melphalan delivered by intravenous, periocular, ophthalmic artery, and intravitreal routes.

Simultaneous Bilateral Ophthalmic Artery Chemosurgery for Bilateral Retinoblastoma (Tandem Therapy).

Objective: Report on the 7-year experience with bilateral ophthalmic artery chemosurgery (OAC-Tandem therapy) for bilateral retinoblastoma.

Design: Retrospective, single institution study.

Subjects: 120 eyes of 60 children with bilateral retinoblastoma treated since March 2008.

Advanced Unilateral Retinoblastoma: The Impact of Ophthalmic Artery Chemosurgery on Enucleation Rate and Patient Survival at MSKCC.

Purpose: To report on the influence of ophthalmic artery chemosurgery (OAC) on enucleation rates, ocular and patient survival from metastasis and impact on practice patterns at Memorial Sloan Kettering for children with advanced intraocular unilateral retinoblastoma.

Patients And Methods: Single-center retrospective review of all unilateral retinoblastoma patients with advanced intraocular retinoblastoma treated at MSKCC between our introduction of OAC (May 2006) and December 2014. End points were ocular survival, patient survival from metastases and enucleation rates.

Loss of the tyrosine phosphatase PTPRD leads to aberrant STAT3 activation and promotes gliomagenesis.

PTPRD, which encodes the protein tyrosine phosphatase receptor-δ, is one of the most frequently inactivated genes across human cancers, including glioblastoma multiforme (GBM). PTPRD undergoes both deletion and mutation in cancers, with copy number loss comprising the primary mode of inactivation in GBM. However, it is unknown whether loss of PTPRD promotes tumorigenesis in vivo, and the mechanistic basis of PTPRD function in tumors is unclear.

Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine.

Mutation in the IDH1 or IDH2 genes occurs frequently in gliomas and other human malignancies. In intermediate grade gliomas, IDH1 mutation is found in over 70% of tumors. These mutations impart the mutant IDH enzyme with a neomorphic activity - the ability to synthesize 2-hydroxyglutarate (2-HG).

5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft.

Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from α-ketoglutarate by the mutant enzyme. 2-HG is an "oncometabolite" that competitively inhibits α-KG dependent dioxygenases resulting in various widespread cellular changes including abnormal hypermethylation of genomic DNA and suppression of cellular differentiation. Despite the growing understanding of IDH mutant gliomas, the development of effective therapies has proved challenging in part due to the scarcity of endogenous mutant in vivo models.

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.

Both genome-wide genetic and epigenetic alterations are fundamentally important for the development of cancers, but the interdependence of these aberrations is poorly understood. Glioblastomas and other cancers with the CpG island methylator phenotype (CIMP) constitute a subset of tumours with extensive epigenomic aberrations and a distinct biology. Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathogenicity, but the molecular basis of G-CIMP remains unresolved.

Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase A oncogene.

Background: Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown.

Interleukin-1R-associated kinase 2 is a novel modulator of the transforming growth factor beta signaling cascade.

The transforming growth factor beta (TGFbeta) pathway orchestrates an extensive transcriptional program that is important for many processes in the cell. For example, TGFbeta regulates cell cycle, migration, and epithelial-to-mesenchymal transition. The TGFbeta pathway has a dual role in cancer: it is involved in early-stage tumor suppression but also contributes to tumor progression by promoting invasion.

A large scale shRNA barcode screen identifies the circadian clock component ARNTL as putative regulator of the p53 tumor suppressor pathway.

Background: The p53 tumor suppressor gene is mutated in about half of human cancers, but the p53 pathway is thought to be functionally inactivated in the vast majority of cancer. Understanding how tumor cells can become insensitive to p53 activation is therefore of major importance. Using an RNAi-based genetic screen, we have identified three novel genes that regulate p53 function.

An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors.

The identification of the cellular targets of small molecules with anticancer activity is crucial to their further development as drug candidates. Here, we present the application of a large-scale RNA interference-based short hairpin RNA (shRNA) barcode screen to gain insight in the mechanism of action of nutlin-3 (1). Nutlin-3 is a small-molecule inhibitor of MDM2, which can activate the p53 pathway.

Direct-to-consumer communication on prescription only medicines via the internet in the Netherlands, a pilot study. Opinion of the pharmaceutical industry, patient associations and support groups.

Objective: Investigation of the current application of direct-to-consumer (DTC) communication on prescription only medicines via the Intemet in the Netherlands.

Method: Questionnaires were sent by e-mail to 43 Dutch innovative pharmaceutical industries and 130 Patient Association and Support Groups (PASGs).

Results: In this pilot study, the response of the pharmaceutical industry was rather low but the impression is that they were willing to invest in DTC communication.