MedWorm: Eye Cancers

Population‐based survival for childhood cancer patients diagnosed during 2002–2005 in Shanghai, China

Pediatric Blood and Cancer — Sun, 05 Feb 2012 12:57:12 +0100

ConclusionsThe survival rate for children aged 0–14 diagnosed with cancer in Shanghai during 2002–2005 was at the medium level. There was a substantial survival difference from childhood cancers between Shanghai and specific developed countries. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

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Differential Expression of Folate Receptor-Alpha, Sodium-Dependent Multivitamin Transporter, and Amino Acid Transporter (B (0, +)) in Human Retinoblastoma (Y-79) and Retinal Pigment Epithelial (ARPE-19) Cell Lines

Journal of Ocular Pharmacology and Therapeutics — Fri, 03 Feb 2012 14:50:57 +0100

Journal of Ocular Pharmacology and Therapeutics , Vol. 0, No. 0. (Source: Journal of Ocular Pharmacology and Therapeutics)

Arabidopsis E2FA stimulates proliferation and endocycle separately through RBR-bound and RBR-free complexes

The EMBO Journal AOP — Fri, 03 Feb 2012 05:00:00 +0100

Authors: Zoltán Magyar, Beatrix Horváth, Safina Khan, Binish Mohammed, Rossana Henriques, Lieven De Veylder, László Bakó, Ben Scheres & László Bögre (Source: The EMBO Journal AOP)

Predictors of long‐term visual outcome after chemoreduction for management of intraocular retinoblastoma

Clinical and Experimental Ophthalmology — Thu, 02 Feb 2012 05:00:00 +0100

Conclusions: Long‐term ambulatory vision (> 20/200) was achieved in the majority (71%) of retinoblastoma containing eyes not requiring enucleation after treatment with chemoreduction and adjunctive therapy. Absence of foveolar involvement and greater number of tumors were the predictor of long‐ term visual outcome of 20/40 or better.© 2012 The Authors. Journal compilation © 2012 Royal Australian and New Zealand College of Ophthalmologists (Source: Clinical and Experimental Ophthalmology)

PP1 and PP2A phosphatases: cooperating partners in modulating retinoblastoma protein activation

FEBS Journal — Wed, 01 Feb 2012 05:00:00 +0100

Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

In this study, we investigated gene copy number and CpG methylation status in CRPC to gain insight into specific pathophysiologic pathways that are active in this advanced form of prostate cancer. Our analysis defined and validated 495 genes exhibiting significant differences in CRPC in gene copy number, including gains in androgen receptor (AR) and losses of PTEN and retinoblastoma 1 (RB1). Significant copy number differences existed between tumors with or without AR gene amplification, including a common loss of AR repressors in AR-unamplified tumors. Simultaneous gene methylation and allelic deletion occurred frequently in RB1 and HSD17B2, the latter of which is involved in testosterone metabolism. Lastly, genomic DNA from most CRPC was hypermethylated compared with benign prostate tiss...

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Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses [Microbiology]

Proceedings of the National Academy of Sciences — Tue, 31 Jan 2012 05:00:00 +0100

More than 120 human papillomaviruses (HPVs) have now been identified and have been associated with a variety of clinical lesions. To understand the molecular differences among these viruses that result in lesions with distinct pathologies, we have begun a MS-based proteomic analysis of HPV–host cellular protein interactions and have created the plasmid and cell line libraries required for these studies. To validate our system, we have characterized the host cellular proteins that bind to the E7 proteins expressed from 17 different HPV types. These studies reveal a number of interactions, some of which are conserved across HPV types and others that are unique to a single HPV species or HPV genus. Binding of E7 to UBR4/p600 is conserved across all virus types, whereas the cellular protein ...

Sulforaphane Inhibits Mitotic Clonal Expansion During Adipogenesis Through Cell Cycle Arrest.

Obesity — Thu, 26 Jan 2012 05:00:00 +0100

In this study, the inhibitory effect of sulforaphane, an isothiocyanate, on adipogenesis in 3T3-L1 cells was investigated. Sulforaphane decreased the accumulation of lipid droplets stained with Oil Red O and inhibited the elevation of triglycerides in the adipocytes (half-maximal inhibitory concentration = 7.3 µmol/l). The expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), major transcription factors for adipocyte differentiation, was significantly reduced by sulforaphane. The major effects of sulforaphane on the inhibition of adipocyte differentiation occurred during the early stage of adipogenesis. Thus, the expression of C/EBPβ, an early-stage biomarker of adipogenesis, decreased in a concentration-dependent manner whe...

Epigenetic and Copy Number Variation Analysis in Retinoblastoma by MS-MLPA.

Pathology Oncology Research — Thu, 26 Jan 2012 05:00:00 +0100

This study also confirms the presence of copy number variations in retinoblastoma, expecially in unilateral cases (mean 3 ±1.3) where these changes were found more frequently respect to bilateral cases (mean 1.4 ± 1.1). PMID: 22278416 [PubMed - as supplied by publisher] (Source: Pathology Oncology Research)

Retinoblastoma: Epigenetic outcome

Nature Reviews Cancer — Tue, 24 Jan 2012 05:00:00 +0100

Nature Reviews Cancer 12, 80 (2012). doi:10.1038/nrc3222 Author: Nicola McCarthy Whole-genome sequencing indicates few genetic changes in retinoblastoma and hints at epigenetic changes instead. (Source: Nature Reviews Cancer)

The genetics of uveal melanoma: an emerging framework for targeted therapy

Pigment Cell Research — Mon, 23 Jan 2012 05:00:00 +0100

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The genetics of uveal melanoma: an emerging framework for targeted therapy.

Pigment Cell and Melanoma Research — Mon, 23 Jan 2012 05:00:00 +0100

This article will review the genetic findings in uveal melanoma over the past two decades and suggest important areas for future work. © 2012 John Wiley & Sons A/S. PMID: 22268848 [PubMed - as supplied by publisher] (Source: Pigment Cell and Melanoma Research)

Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments

Acta Ophthalmologica — Mon, 23 Jan 2012 05:00:00 +0100

Conclusion: Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents. (Source: Acta Ophthalmologica)

Comparison of Clinical Outcomes for Patients with Large Choroidal Melanoma after Primary Treatment with Enucleation or Proton Beam Radiotherapy

Ophthalmologica — Thu, 19 Jan 2012 23:00:00 +0100

Ophthalmologica (DOI:10.1159/000334401) (Source: Ophthalmologica)

Molecular study of retinoblastoma in the Algerian population. Screening of Rb gene in constitutional and tumoral level.

Bulletin du Cancer — Thu, 19 Jan 2012 05:00:00 +0100

In this report, we present the results of a constitutionnal and tumoral RB1 analysis in Algerian population. The detection of RB1 gene deletion or mutation was performed by high performance liquid chromatography (HPLC) and sequence analyses in 21 patients. Germline abnormalities were found in 2/21 patients of sporadic unilateral retinoblastoma. The spectrum of germline and tumoral alterations included: three nonsense mutations; one mutation affecting splice site; one deletion and two polymorphisms. In general, for the 21 patients with no family history of the disease, we have identified mutations in germinal level in two of them showing that it is a transmissible form of retinoblastoma in these two cases known to be sporadic. A total of two mutations have not been previously reported. ...

ID2: A negative transcription factor regulating oligodendroglia differentiation

Journal of Neuroscience Research — Wed, 18 Jan 2012 05:00:00 +0100

AbstractRemyelination of the central nervous system in multiple sclerosis patients is often incomplete. Remyelination depends on normal oligodendrogenesis and the differentiation of oligodendrocyte precursor cells (OPC) into mature oligodendrocytes (OL). Inhibitor of DNA binding (ID), a transcription factor, is thought to inhibit oligodendrogenesis and the differentiation of OPC. This Mini‐Review aims to reveal the roles of and mechanisms used by IDs (mainly ID2) in this process. An interaction between ID2 and retinoblastoma tumor suppressor is responsible for the cell cycle transition from G1 to S. The translocation of ID2 between the nucleus and cytoplasm is regulated by E47 and OLIG. An interaction between ID2 and OLIG mediates the inhibitory effects of bone morphogenic proteins and G...

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Genomics: The path to retinoblastoma

Nature — Wed, 18 Jan 2012 05:00:00 +0100

Authors: Julien Sage & Michael L. Cleary Genomic analyses of tumours of the childhood cancer retinoblastoma reveal a low mutation rate, challenging the view that genomic instability is crucial for its progression. The work also identifies a new therapeutic target. See Article p.329 (Source: Nature)

Regulation of Matrix Metalloproteinase Genes by E2F Transcription Factors: Rb-Raf-1 Interaction as a Novel Target for Metastatic Disease

Cancer Research — Mon, 16 Jan 2012 05:00:00 +0100

The retinoblastoma (Rb)–E2F transcriptional regulatory pathway plays a major role in cell-cycle regulation, but its role in invasion and metastasis is less well understood. We find that many genes involved in the invasion of cancer cells, such as matrix metalloproteinases (MMP), have potential E2F-binding sites in their promoters. E2F-binding sites were predicted on all 23 human MMP gene promoters, many of which harbored multiple E2F-binding sites. Studies presented here show that MMP genes such as MMP9, MMP14, and MMP15 which are overexpressed in non–small cell lung cancer, have multiple E2F-binding sites and are regulated by the Rb–E2F pathway. Chromatin immunoprecipitation assays showed the association of E2F1 with the MMP9, MMP14, and MMP15 promoters, and transient transfection e...

Inducible Deletion of Rb in Enterocytes Enhances Adaptation After Small Bowel Resection

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:04 +0100

Conclusions: Deletion of Rb after SBR, but not prior results in amplified intestinal adaptation. These findings implicate an important regulatory role for Rb in the genesis of this important response and underscore the significance of postoperative timing for interventions intended to enhance resection-induced adaptation in patients suffering from short gut syndrome. (Source: Journal of Surgical Research)

Simulation and dosimetric analysis of proton and carbon ion therapy in the treatment of uveal melanoma

Radiologia Brasileira — Sat, 14 Jan 2012 19:42:51 +0100

CONCLUSION: The described benefits together with the presented results contribute to the development of clinical applications and researches on carbon ion and proton therapy. (Source: Radiologia Brasileira)

Gene identified as a new target for treatment of aggressive childhood eye tumor

ScienceDaily Headlines — Sat, 14 Jan 2012 01:54:54 +0100

New findings help solve mystery of retinoblastoma's rapid growth in work that also yields a new treatment target and possible therapy. (Source: ScienceDaily Headlines)

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Potential New Treatment Target for RetinoblastomaPotential New Treatment Target for Retinoblastoma

Medscape Today Headlines — Fri, 13 Jan 2012 14:39:05 +0100

Genetic sequencing has identified an unexpected target for which experimental drugs are already being tested. Medscape Medical News (Source: Medscape Today Headlines)

Gene Identified As A New Target For Treatment Of Aggressive Childhood Eye Tumor

Health News from Medical News Today — Fri, 13 Jan 2012 08:00:00 +0100

St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project findings help solve mystery of retinoblastoma's rapid growth in work that also yields a new treatment target and possible therapy New findings from the St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project (PCGP) have helped identify the mechanism that makes the childhood eye tumor retinoblastoma so aggressive. The discovery explains why the tumor develops so rapidly while other cancers can take years or even decades to form... (Source: Health News from Medical News Today)

Single-Shot Turbo Spin-Echo Diffusion-Weighted Imaging for Retinoblastoma: Initial Experience [HEAD AND NECK]

American Journal of Neuroradiology — Thu, 12 Jan 2012 05:00:00 +0100

CONCLUSIONS: HASTE DWI allowed adequate characterization of retinoblastoma, and ADC is a helpful tool to differentiate viable and necrotic tumor tissue and might be valuable in monitoring the response to eye-preserving therapies. (Source: American Journal of Neuroradiology)

Genetic and Molecular Characterization of Uveal Melanoma Cell Lines

Pigment Cell Research — Wed, 11 Jan 2012 05:00:00 +0100

We report the mutation status of relevant melanoma genes, expression levels of proteins of interest and DNA fingerprinting of a panel of uveal melanoma cell lines used in the research community. (Source: Pigment Cell Research)

Gene identified as a new target for treatment of aggressive childhood eye tumor

EurekAlert! - Cancer — Wed, 11 Jan 2012 05:00:00 +0100

(St. Jude Children's Research Hospital) New findings from the St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project have helped identify the mechanism that makes the childhood eye tumor retinoblastoma so aggressive. (Source: EurekAlert! - Cancer)

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A novel retinoblastoma therapy from genomic and epigenetic analyses

Nature AOP — Wed, 11 Jan 2012 05:00:00 +0100

Authors: Jinghui Zhang, Claudia A. Benavente, Justina McEvoy, Jacqueline Flores-Otero, Li Ding, Xiang Chen, Anatoly Ulyanov, Gang Wu, Matthew Wilson, Jianmin Wang, Rachel Brennan, Michael Rusch, Amity L. Manning, Jing Ma, John Easton, Sheila Shurtleff, Charles Mullighan, Stanley Pounds, Suraj Mukatira, Pankaj Gupta, Geoff Neale, David Zhao, Charles Lu, Robert S. Fulton, Lucinda L. Fulton, Xin Hong, David J. Dooling, Kerri Ochoa, Clayton Naeve, Nicholas J. Dyson, Elaine R. Mardis, Armita Bahrami, David Ellison, Richard K. Wilson, James R. Downing & Michael A. Dyer (Source: Nature AOP)

Current status of molecular markers for prognostication and outcome in invasive bladder cancer

BJU International — Wed, 11 Jan 2012 05:00:00 +0100

CONCLUSIONS• Different molecular markers have the potential to improve prognostication of patients with invasive BC and provide improved evidence for targeted therapy in the neoadjuvant, adjuvant and metastatic setting.• However, in order to advocate their routine clinical use on a sound scientific basis prospective data are still necessary. (Source: BJU International)

Genetic and Molecular Characterization of Uveal Melanoma Cell Lines.

Pigment Cell and Melanoma Research — Wed, 11 Jan 2012 05:00:00 +0100

A novel retinoblastoma therapy from genomic and epigenetic analyses

Nature — Wed, 11 Jan 2012 05:00:00 +0100

The PPARδ ligand L‐165041 inhibits VEGF‐induced angiogenesis, but the antiangiogenic effect is not related to PPARδ

Journal of Cellular Biochemistry — Tue, 10 Jan 2012 05:00:00 +0100

This study highlights the therapeutic potential of L‐165041 in the treatment of many disorders related to pathological angiogenesis. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc. (Source: Journal of Cellular Biochemistry)

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Malignant melanoma as second malignant neoplasm in long‐term childhood cancer survivors: A systematic review

Pediatric Blood and Cancer — Mon, 09 Jan 2012 05:00:00 +0100

AbstractThis systematic review provides information on malignant melanoma as second malignant neoplasm (SMN) after childhood cancer and evaluates its risk factors. Study reports describing incidences of SMN and malignant melanoma as SMN in a population of childhood cancer survivors (CCS) were included. Of 151,575 CCS, 4,010 (2.6%) children developed an SMN, 212 of which were melanoma (5.3% or 0.14% of all CCS). The following risk factors for malignant melanoma as SMN were identified: radiotherapy, or the combination alkylating agents and anti‐mitotic drugs. Melanomas are most frequently observed after Hodgkin disease, hereditary retinoblastoma, soft tissue sarcoma, and gonadal tumors. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Clinical and Pathologic Characteristics of Biopsy-Proven Iris Melanoma: A Multicenter International Study [Clinical Sciences]

Archives of Opthalmology — Mon, 09 Jan 2012 05:00:00 +0100

Conclusions Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris. (Source: Archives of Opthalmology)

Chromosome instability and deregulated proliferation: an unavoidable duo.

Cellular and Molecular Life Sciences : CMLS — Fri, 06 Jan 2012 05:00:00 +0100

Authors: Coschi CH, Dick FA Abstract The concept that aneuploidy is a characteristic of malignant cells has long been known; however, the idea that aneuploidy is an active contributor to tumorigenesis, as opposed to being an associated phenotype, is more recent in its evolution. At the same time, we are seeing the emergence of novel roles for tumor suppressor genes and oncogenes in genome stability. These include the adenomatous polyposis coli gene (APC), p53, the retinoblastoma susceptibility gene (RB1), and Ras. Originally, many of these genes were thought to be tumor suppressive or oncogenic solely because of their role in proliferative control. Because of the frequency with which they are disrupted in cancer, chromosome instability caused by their dysfunction may be more centra...

Notch signaling promotes growth and invasion in uveal melanoma.

Clinical Cancer Research — Fri, 06 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our findings suggest that Notch plays an important role in inducing proliferation and invasion in uveal melanoma, and that inhibiting this pathway may be effective in preventing tumor growth and metastasis. PMID: 22228632 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Intra-ophthalmic artery melphalan effective for refractory retinoblastoma

Modern Medicine — Thu, 05 Jan 2012 05:00:00 +0100

NEW YORK (Reuters Health) - Super-selective intra-ophthalmic artery melphalan (IAM) treatment achieves a high level of remission in children with refractory retinoblastoma, UK researchers report in a paper online December 22 in Ophthalmology. (Source: Modern Medicine)

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Serum DJ-1/PARK 7 Is a Potential Biomarker of Choroidal Nevi Transformation [Anatomy and Pathology]

Investigative Ophthalmology — Thu, 05 Jan 2012 05:00:00 +0100

Conclusions. Elevated serum levels of DJ-1 are associated with choroidal nevi transformation risk factors. Therefore, DJ-1 appears to be a promising factor for predicting the growth of choroidal nevi and may be a potential biomarker of malignancy. (Source: Investigative Ophthalmology)

A Novel Method of Transcriptional Response Analysis to Facilitate Drug Repositioning for Cancer Therapy

Cancer Research — Mon, 02 Jan 2012 05:00:00 +0100

In this study, we addressed this critical gap by developing an OTE-based method to repurpose drugs for cancer therapeutics, based on transcriptional responses made in cells before and after drug treatment. Specifically, we defined a new network component called cancer-signaling bridges (CSB) and integrated it with a Bayesian factor regression model (BFRM) to form a new hybrid method termed CSB-BFRM. Proof-of-concept studies were conducted in breast and prostate cancer cells and in promyelocytic leukemia cells. In each system, CSB-BFRM analysis could accurately predict clinical responses to more than 90% of drugs approved by the U.S. Food and Drug Administration and more than 75% of experimental clinical drugs that were tested. Mechanistic investigation of OTEs for several high-ranking drug...

Contrasting Behavior of the p18INK4c and p16INK4a Tumor Suppressors in Both Replicative and Oncogene-Induced Senescence

Cancer Research — Mon, 02 Jan 2012 05:00:00 +0100

The cyclin-dependent kinase (CDK) inhibitors, p18INK4c and p16INK4a, both have the credentials of tumor suppressors in human cancers and mouse models. For p16INK4a, the underlying rationale is its role in senescence, but the selective force for inactivation of p18INK4c in incipient cancer cells is less clear. Here, we show that in human fibroblasts undergoing replicative or oncogene-induced senescence, there is a marked decline in the levels of p18INK4c protein and RNA, which mirrors the accumulation of p16INK4a. Downregulation of INK4c is not dependent on p16INK4a, and RAS can promote the loss of INK4c without cell-cycle arrest. Downregulation of p18INK4c correlates with reduced expression of menin and E2F1 but is unaffected by acute cell-cycle arrest or inactivation of the retinoblastoma...

[Effects of extracts from Panax ginseng, Panax notoginseng and Ligusticum chuanxiong on expression of β-galactosidase and signal pathway p16-cyclin D/CDK-Rb in vascular smooth muscle cells].

Zhong xi yi jie he xue bao : Journal of Chinese Integrative Medicine. — Sun, 01 Jan 2012 05:00:00 +0100

CONCLUSION: The extracts from Panax ginseng, Panax notoginseng (Burk.) and Ligusticum chuanxiong can delay vascular aging of SHRs, which works by p16-cyclin D/CDK-RB pathways to inhibit VSMC proliferation. PMID: 22237278 [PubMed - in process] (Source: Zhong xi yi jie he xue bao : Journal of Chinese Integrative Medicine.)

Altered methylation at microRNA-associated CpG islands in hereditary and sporadic carcinomas: a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)-based approach.

Molecular Medicine — Thu, 29 Dec 2011 07:24:03 +0100

Authors: Pavicic W, Perkiö E, Kaur S, Peltomäki P Abstract MicroRNAs (miRNAs) are small noncoding RNAs that contribute to tumorigenesis by acting as oncogenes or tumor suppressor genes and may be important in the diagnosis, prognosis and treatment of cancer. Many miRNA genes have associated CpG islands, suggesting epigenetic regulation of their expression. Compared with sporadic cancers, the role of miRNAs in hereditary or familial cancer is poorly understood. We investigated 96 colorectal carcinomas, 58 gastric carcinomas and 41 endometrial carcinomas, occurring as part of inherited DNA mismatch repair (MMR) deficiency (Lynch syndrome), familial colorectal carcinoma without MMR gene mutations or sporadically. Methylation-specific multiplex ligation-dependent probe amplification ...

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Indoxyl Sulfate Induces Nephrovascular Senescence

Journal of Renal Nutrition — Thu, 29 Dec 2011 05:37:04 +0100

Indoxyl sulfate is markedly accumulated in the serum of chronic kidney disease (CKD) patients. The oral sorbent AST-120 reduces serum levels of indoxyl sulfate in CKD patients by adsorbing indole, a precursor of indoxyl sulfate, in the intestine. Indoxyl sulfate is taken up by proximal tubular cells through organic anion transporters (OAT1, OAT3), and it induces reactive oxygen species (ROS) with impairment of cellular antioxidative system. Indoxyl sulfate stimulates progression of CKD by increasing renal expression of profibrotic cytokines such as transforming growth factor beta 1. Further, it promotes the expression of p53 by ROS-induced activation of nuclear factor kappa B, thereby accelerating senescence of proximal tubular cells with progression of CKD. Administration of indoxyl sulfa...

Neferine, an alkaloid ingredient in lotus seed embryo, inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization.

European Journal of Pharmacology — Thu, 29 Dec 2011 05:00:00 +0100

In this report we studied the effects of neferine, a major alkaloid component in lotus embryos, on human osteosarcoma cells and the underlying mechanisms. We found that neferine possessed a potent growth-inhibitory effect on human osteosarcoma cells, but not on non-neoplastic human osteoblast cells. The inhibitory effect of neferine on human osteosarcoma cells was largely attributed to cell cycle arrest at G1. The induction of G1 arrest was p21(WAF1/CIP1)-dependent, but was independent of p53 or RB (retinoblastoma-associated protein). The up-regulation of p21 by neferine was due to an increase in the half-life of p21 protein. We examined four kinases that are known to affect the stabilization of p21, and found that p38 MAPK and JNK were activated by neferine. However, only SB203580 (an inh...

Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen.

Archives of Biochemistry and Biophysics — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Williams CK, Vathiyalingam S, Hammel M, Pipas J, Chazin WJ Abstract Simian Virus 40 uses the large T antigen (Tag) to bind and inactivate retinoblastoma tumor suppressor proteins (Rb), which can result in cellular transformation. Tag is a modular protein with four domains connected by flexible linkers. The N-terminal J domain of Tag is necessary for Rb inactivation. Binding of Rb is mediated by an LXCXE consensus motif immediately C-terminal to the J domain. Nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) were used to study the structural dynamics and interaction of Rb with the LXCXE motif, the J domain and a construct (N(260)) extending from the J domain through the origin binding domain (OBD). NMR and SAXS data revealed substantial flexibility be...

RB1 mutations and second primary malignancies after hereditary retinoblastoma

Familial Cancer — Wed, 28 Dec 2011 16:52:19 +0100

Abstract Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199 survivors of hereditary retinoblastoma with a documented RB1 germline mutation diagnosed between 1905 and 2005. In total, 44 hereditary retinoblastoma survivors developed a second primary malignancy after a median follow-up of 30.2 years (range 1.33–76.0). A significantly increased risk of second primary malignancy was observed among carriers of one of the 11 recurrent CGA>TGA nonsense RB1 mutations (hazard ratio (HR) = 3.53; [95% confidence interval (CI)&nbs...

Influence of retinoblastoma-related gene silencing on the initiation of DNA replication by African cassava mosaic virus Rep in cells of mature leaves in Nicotiana benthamiana plants

BioMed Central — Wed, 28 Dec 2011 05:00:00 +0100

Conclusions: These results suggest that the cellular machinery for DNA replication in differentiated tissues of older leaves cannot be reprogrammed by Rep alone but may need other uncharacterised viral and plant factors. (Source: BioMed Central)

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Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors

Human Genetics — Tue, 27 Dec 2011 17:04:34 +0100

Abstract Autosomal dominant conditions are known to be associated with advanced paternal age, and it has been suggested that retinoblastoma (Rb) also exhibits a paternal age effect due to the paternal origin of most new germline RB1 mutations. To further our understanding of the association of parental age and risk of de novo germline RB1 mutations, we evaluated the effect of parental age in a cohort of Rb survivors in the United States. A cohort of 262 Rb patients was retrospectively identified at one institution, and telephone interviews were conducted with parents of 160 survivors (65.3%). We classified Rb survivors into three groups: those with unilateral Rb were classified as sporadic if they had no or unknown family history of Rb, those with bilateral Rb were classifie...

ORNL Image Analysis Prowess Advances Retina Research

Health News from Medical News Today — Tue, 27 Dec 2011 08:00:00 +0100

Armed with a new ability to find retinal anomalies at the cellular level, neurobiologists at St. Jude Children's Research Hospital have made a discovery they hope will ultimately lead to a treatment for cancer of the retina. While much work remains, Oak Ridge National Laboratory's specialized tracing algorithm allows researchers to analyze thousands of cells instead of just a few dozen. This tool has helped reveal a previously undiscovered role of Rb, the retinoblastoma tumor suppressor gene in the developing retina... (Source: Health News from Medical News Today)

Retinoblastoma (Rb) regulates laminar dendritic arbor reorganization in retinal horizontal neurons [Developmental Biology]

Proceedings of the National Academy of Sciences — Tue, 27 Dec 2011 05:00:00 +0100

Neuronal differentiation with respect to the acquisition of synaptic competence needs to be regulated precisely during neurogenesis to ensure proper formation of circuits at the right place and time in development. This regulation is particularly important for synaptic triads among photoreceptors, horizontal cells (HCs), and bipolar cells in the retina, because HCs are among the first cell types produced during development, and bipolar cells are among the last. HCs undergo a dramatic transition from vertically oriented neurites that form columnar arbors to overlapping laminar dendritic arbors with differentiation. However, how this process is regulated and coordinated with differentiation of photoreceptors and bipolar cells remains unknown. Previous studies have suggested that the retinobl...

ORNL Image Analysis Prowess Advances Retina Research

Health News from Medical News Today — Sat, 24 Dec 2011 08:00:00 +0100

Dosimetric Study of Current Treatment Options for Radiotherapy in Retinoblastoma

International Journal of Radiation Oncology * Biology * Physics — Fri, 23 Dec 2011 05:00:00 +0100

Conclusions: Inverse planned image-guided radiotherapy delivered using HT or VMAT gives better conformity index, improved orbital bone and brain sparing, and a lower integral dose than other techniques. (Source: International Journal of Radiation Oncology * Biology * Physics)

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The role of nuclear lamin B1 in cell proliferation and senescence [Research Papers]

Genes and Development — Wed, 21 Dec 2011 05:00:00 +0100

Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (RO...

Bilateral Diffuse Uveal Melanocytic Proliferation Presenting as Small Choroidal Melanoma

Computational Intelligence and Neuroscience — Tue, 20 Dec 2011 23:48:40 +0100

Conclusion. BDUMP should always be considered in the differential diagnosis of patients with pigmented fundus lesions and a history of nonocular tumors. (Source: Computational Intelligence and Neuroscience)

Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations

Familial Cancer — Tue, 20 Dec 2011 16:43:50 +0100

Abstract The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of “other cancers” in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1–6.0) and stomach at 2.4 (95% CI 1.2–4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9–7.8)...

Retinoblastoma with coats' response.

Tue, 20 Dec 2011 14:06:02 +0100

Authors: Silva RA, Dubovy SR, Fernandes CE, Hess DJ, Murray TG Abstract Although it is well known that a variety of pediatric ocular diseases may clinically resemble retinoblastoma, perhaps of more concern is when the actual tumor mimics seemingly benign ocular lesions. The authors present two cases of retinoblastoma with a Coats' response as evidence of the challenge often encountered in evaluating intraocular malignancies. The cases further emphasize the need for retaining a high level of clinical suspicion for more malicious diseases, often using repeated fundus evaluations when a diagnosis remains ambiguous. PMID: 22165951 [PubMed - in process] (Source: Ophthalmic Surgery, Lasers and Imaging : the Official Journal of the International Society for Imaging in the Eye)

Costimulatory molecule expression on human uveal melanoma cells: Functional analysis of CD40 and B7-H1.

Experimental Eye Research — Tue, 20 Dec 2011 05:00:00 +0100

In this study, we investigated costimulatory molecule expression on human uveal melanoma cells (a primary culture, and OCM-1, OMM-1 and 92-1 cell lines) and assessed the functional roles of selected costimulatory molecules. Uveal melanoma cells were incubated in the presence or absence of IFN-γ and expression of costimulatory molecules on the cells was measured by flow cytometry. The costimulatory effect of B7-H1-expressing uveal melanoma cells on cytokine production by purified T cells was studied in uveal melanoma/T cell co-culture experiments using a blocking anti-B7-H1 monoclonal antibody (mAb). The functional role of CD40-mediated interactions in modifying immune responses to uveal melanoma cells was assessed in vitro using recombinant human CD40 ligand (rhCD40L). MHC class I and B7...

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Researchers Discover Hereditary Predisposition Of Melanoma Of The Eye

Health News from Medical News Today — Mon, 19 Dec 2011 08:00:00 +0100

Ohio State University researchers have discovered a hereditary cancer syndrome that predisposes certain people to a melanoma of the eye, along with lung cancer, brain cancer and possibly other types of cancer. The hereditary cancer syndrome is caused by an inherited mutation in a gene called BAP1, researchers say. The findings suggest that BAP1 mutations cause the disease in a small subset of patients with hereditary uveal melanoma and other cancers. Uveal melanoma is a cancer of the eye involving the iris, ciliary body, or choroid, which are collectively known as the uvea... (Source: Health News from Medical News Today)

Occupational exposure to endocrine-disrupting chemicals and the risk of uveal melanoma.

Scandinavian Journal of Work, Environment and Health — Sat, 17 Dec 2011 05:00:00 +0100

CONCLUSION: Occupational exposure to EDC was not associated with an increased risk for uveal melanoma. PMID: 22179223 [PubMed - as supplied by publisher] (Source: Scandinavian Journal of Work, Environment and Health)

Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma

Pediatric Blood and Cancer — Fri, 16 Dec 2011 05:00:00 +0100

ConclusionOur results indicate that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Therapeutic and Toxicological Evaluation of Anti‐Lipogenic Agents in Cancer Cells Compared with Non‐Neoplastic Cells

Basic and Clinical Pharmacology and Toxicology — Tue, 13 Dec 2011 07:08:29 +0100

AbstractFatty acid synthase (FASN), a multi‐enzyme complex, is involved in lipid biosynthesis. FASN is over‐expressed in different types of cancers and is being widely investigated for its role in cancer progression, diagnosis and therapy. Here, three inhibitors targeting different domains of FASN — cerulenin, triclosan and orlistat — were evaluated for their anti‐proliferative efficacy in ocular cancer, retinoblastoma (RB) cells and their toxicity (if any) in normal cells. FASN inhibitors were tested in cultured retinoblastoma Y79 cells, normal fibroblast (3T3) and Müller glial (MIOM1) cells. Cell viability was determined by MTT‐based assay, and IC50 (50% inhibitory concentration) of the FASN inhibitors was calculated in neoplastic and non‐neoplastic cells. The IC50 after 4...

Mitotic checkpoints and chromosome instability are strong predictors of clinical outcome in gastrointestinal stromal tumors.

Clinical Cancer Research — Tue, 13 Dec 2011 05:00:00 +0100

CONCLUSIONS: We propose that a high Genomic Index determined by Comparative Genomic Hybridisation (CGH) from formalin-fixed paraffin-embedded samples could be used to identify AFIP intermediate-risk patients who would benefit from imatinib therapy. PMID: 22167411 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Massive choroidal effusion and painful secondary glaucoma from underlying uveal melanoma

Graefe's Archive for Clinical and Experimental Ophthalmology — Mon, 12 Dec 2011 06:33:10 +0100

Content Type Journal ArticleCategory Case ReportPages 1-4DOI 10.1007/s00417-011-1881-8Authors Juan C. Iturralde, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USACarlos Bianciotto, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USASara E. Lally, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USAMichael Krasnow, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USACarol L. Shields, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, USA Journal Graefe's Archive for Clinical and Experimental OphthalmologyOnline ISSN 1435-702XPrint ISSN 0721-832X (Source: Graefe's Archive for Clinic...

Erratum to: Access to the ophthalmic artery by retrograde approach through the posterior communicating artery for intra-arterial chemotherapy of retinoblastoma

Neuroradiology — Mon, 12 Dec 2011 06:32:49 +0100

Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s00234-011-0991-7Authors Chi-Tuan Pham, Department of Interventional Neuroradiology, Fondation, Rothschild Hospital, 25 rue Manin, Paris, FranceRaphaël Blanc, Department of Interventional Neuroradiology, Fondation, Rothschild Hospital, 25 rue Manin, Paris, FranceLivia Lumbroso-Le Rouic, Department of Ocular Oncology, Institut Curie, 26 rue d’Ulm, Paris, FranceSilvia Pistocchi, Department of Interventional Neuroradiology, Fondation, Rothschild Hospital, 25 rue Manin, Paris, FranceBruno Bartolini, Department of Interventional Neuroradiology, Fondation, Rothschild Hospital, 25 rue Manin, Paris, FranceMichel Piotin, Department of Interventional Neuroradiology, Fondation, Rothschild Hospital, 25 rue Manin, Paris, France ...

Characterization of Computed Tomography Scan Abnormalities in Patients With Biopsy-Proven Hepatic Metastases From Uveal Melanoma [Clinical Sciences]

Archives of Opthalmology — Mon, 12 Dec 2011 05:00:00 +0100

Conclusions Radiographic evidence of predominant lesion size larger than 100 cm2, hepatomegaly, and ascites—but not radiographic evidence of extrahepatic metastases—correlate with a lower survival rate in patients with biopsy-proven hepatic metastases of uveal melanoma. (Source: Archives of Opthalmology)

The incidence and distribution of retinoblastoma in Kenya

British Journal of Ophthalmology — Mon, 12 Dec 2011 05:00:00 +0100

We estimated the Kenyan retinoblastoma incidence, and distribution by age, sex, family history, ethnicity and province. A nationwide chart-review identified retinoblastoma cases between 1 January 2006 and 31 December 2007 (supplementary methods). We observed 206 cases in 46 Kenyan healthcare facilities, of which 58 (28%) were lost after referral, and 148 (72%) were traceable (figure 1). We excluded 16 cases, comprising 3 missing files and 13 with histology inconsistent with retinoblastoma (figure 2), leaving 132 cases. The concordance of 91% of available histological reports with the initial clinical diagnosis indicates that initial clinical diagnosis of retinoblastoma is performed adequately. We estimated a total of 84 new retinoblastoma cases in 2007, based on 57 confirmed cases and 27 p...

Modeling Lethal Prostate Cancer Variant with Small Cell Carcinoma Features.

Clinical Cancer Research — Mon, 12 Dec 2011 05:00:00 +0100

CONCLUSION: Modeling human prostate carcinoma with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. PMID: 22156612 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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HPV E7 viral oncoprotein disrupts transcriptional regulation of L1Md retrotransposon

FEBS Letters — Mon, 12 Dec 2011 05:00:00 +0100

Highlights: ► HPV E7 viral oncoprotein ablates L1MdA5 reactivation following genotoxic stress. ► HPV E7 disrupts retinoblastoma-mediated L1MdA5 promoter transactivation. ► The basal and carcinogen-induced activities of L1MdA5 promoter are independent of Rb repressor function. ► HPV E7 disrupts assembly of protein complexes regulating L1MdA5.Abstract: Murine L1Md-A5 retrotransposon is a redox-inducible element regulated by Nrf-2/JunD and E2F/Rb-binding sites within its promoter (5′-UTR). Because the human papillomavirus (HPV) oncoprotein E7 interacts with retinoblastoma (pRb) and members of the AP1 family, studies were conducted to examine functional interactions between HPV E7, pRb, and histone deacetylase 2 (HDAC2) in the regulation of L1Md-A5. Using a transient heterologous tra...

Therapeutic and Toxicologic Evaluation of Anti‐Lipogenic Agents in Cancer Cells Compared with Non‐Neoplastic Cells

Basic and Clinical Pharmacology and Toxicology — Mon, 12 Dec 2011 05:00:00 +0100

Abstract: Fatty acid synthase (FASN), a multi‐enzyme complex, is involved in lipid biosynthesis. FASN is over‐expressed in different types of cancers and is being widely investigated for its role in cancer progression, diagnosis and therapy. Here, three inhibitors targeting different domains of FASN – cerulenin, triclosan and orlistat – were evaluated for their anti‐proliferative efficacy in ocular cancer, retinoblastoma (RB) cells and their toxicity (if any) in normal cells. FASN inhibitors were tested in cultured retinoblastoma Y79 cells, normal fibroblast (3T3) and Müller glial (MIOM1) cells. Cell viability was determined by MTT‐based assay, and IC50 (50% inhibitory concentration) of the FASN inhibitors was calculated in neoplastic and non‐neoplastic cells. The IC50 af...

Altered calcium regulation by thermosensitive transient receptor potential channels in etoposide-resistant WERI-Rb1 retinoblastoma cells.

Experimental Eye Research — Sun, 11 Dec 2011 05:00:00 +0100

Authors: Mergler S, Cheng Y, Skosyrski S, Garreis F, Pietrzak P, Kociok N, Dwarakanath A, Reinach PS, Kakkassery V Abstract Differences in transient receptor potential (TRP) and cannabinoid receptor type 1 (CB1) expression levels can serve as prognostic factors for retinoblastoma (RB) tumor progression. We hypothesized in RB tissue that such differences are also indicators of whether or not they are sensitive to etoposide. Accordingly, we compared in malignant etoposide-sensitive and etoposide-resistant WERI-Rb1 cells TRPV1, TRPM8 and TRPA1 subtype and CB1 gene expression pattern levels and accompanying functional activity using quantitative real-time RT-PCR, immunohistochemistry, immunofluorescence microscopy, calcium imaging as well as patch-clamp technology. Gene expression patt...

Loss Of RB In Triple Negative Breast Cancer Associated With Favorable Clinical Outcome

Health News from Medical News Today — Sat, 10 Dec 2011 08:00:00 +0100

Researchers at the Thomas Jefferson University Hospital and Kimmel Cancer Center at Jefferson have shown that loss of the retinoblastoma tumor suppressor gene (RB) in triple negative breast cancer patients is associated with better clinical outcomes. This is a new marker to identify the subset of these patients who may respond positively to chemotherapy. Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same. Agnieszka Witkiewicz, M.D... (Source: Health News from Medical News Today)

SABCS: Loss of RB in triple negative breast cancer associated with favorable clinical outcome

EurekAlert! - Medicine and Health — Fri, 09 Dec 2011 05:00:00 +0100

(Thomas Jefferson University) Researchers at the Thomas Jefferson University Hospital and Kimmel Cancer Center at Jefferson have shown that loss of the retinoblastoma tumor suppressor gene in triple negative breast cancer patients is associated with better clinical outcomes. This is a new marker to identify the subset of these patients who may respond positively to chemotherapy. (Source: EurekAlert! - Medicine and Health)

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Carcinoembryonic Antigen Cell Adhesion Molecule-1 (CEACAM1) in Posterior Uveal Melanoma: Correlation with Clinical and Histological Survival Markers [Anatomy and Pathology]

Investigative Ophthalmology — Fri, 09 Dec 2011 05:00:00 +0100

Conclusions. This report describes CEACAM1 expression in uveal melanoma. Correlation with poor prognostic factors such as epithelioid cell type and networks of extracellular matrix pattern was found, but definitive prognostic conclusions still cannot be deduced. Additional validation studies on the use of CEACAM1 expression as a prognostic marker are warranted. (Source: Investigative Ophthalmology)

Does the Time of Inactivation of pRb Determine the Cell of Origin of Retinoblastoma? [Letters]

Investigative Ophthalmology — Fri, 09 Dec 2011 05:00:00 +0100

(Source: Investigative Ophthalmology)

De-regulation of the RBBP6 isoform 3/DWNN in human cancers.

Molecular and Cellular Biochemistry — Sat, 03 Dec 2011 05:00:00 +0100

In conclusion, these findings suggest that RBBP6 isoform 3 is a cell cycle regulator and may be de-regulated in carcinogenesis. PMID: 22139301 [PubMed - as supplied by publisher] (Source: Molecular and Cellular Biochemistry)

The BAP1tism of a Tumor Suppressor.

Clinical Cancer Research — Fri, 02 Dec 2011 05:00:00 +0100

Authors: Woodman SE Abstract Driving cancer cells into a more differentiated state is a rational therapeutic approach. Primary uveal melanoma cells with a propensity to metastasize have less differentiated features than their less aggressive counterparts. Treatment of uveal melanoma cells with histone deacetylase inhibitors induces a more differentiated phenotype with resultant lower growth capacity. PMID: 22140212 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Uveal melanoma in a 19-month-old child

Journal of AAPOS — Thu, 01 Dec 2011 05:00:00 +0100

We report a 19-month-old boy with a choroidal melanoma presenting as hemorrhagic retinal detachment and buphthalmos. The eye was enucleated, but the child subsequently died from systemic metastases. (Source: Journal of AAPOS)

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Spread Of Aggressive Uveal Melanoma Cells May Be Slowed By Seizure Drug

Health News from Medical News Today — Wed, 30 Nov 2011 08:00:00 +0100

A drug commonly used to treat seizures appears to make eye tumors less likely to grow if they spread to other parts of the body, according to researchers at Washington University School of Medicine in St. Louis. Their findings are available online in the journal Clinical Cancer Research. Uveal melanoma, the second most common form of melanoma, can be very aggressive and spread, or metastasize, from the eye to other organs, especially the liver... (Source: Health News from Medical News Today)

Ano1 as a regulator of proliferation

AJP: Gastrointestinal and Liver Physiology — Wed, 30 Nov 2011 05:00:00 +0100

Ano1 is a recently discovered Ca2+-activated Cl– channel expressed on interstitial cells of Cajal (ICC) that has been implicated in slow-wave activity in the gut. However, Ano1 is expressed on all classes of ICC, even those that do not contribute to generation of the slow wave, suggesting that Ano1 may have an alternate function in these cells. Ano1 is also highly expressed in gastrointestinal stromal tumors. Mice lacking Ano1 had fewer proliferating ICC in whole mount preparations and in culture, raising the possibility that Ano1 is involved in proliferation. Cl– channel blockers decreased proliferation in cells expressing Ano1, including primary cultures of ICC and in the pancreatic cancer-derived cell line, CFPAC-1. Cl– channel blockers had a reduced effect on Ano1(&nd...

A Five-Year Study of Slotted Eye Plaque Radiation Therapy for Choroidal Melanoma: Near, Touching, or Surrounding the Optic Nerve

Ophthalmology — Wed, 30 Nov 2011 05:00:00 +0100

Conclusions: Slotted plaque radiation therapy allows peripapillary, juxtapapilary, and circumpapillary choroidal melanomas (and a safety margin) to be included in the radiation targeted zone. Normalization of the plaque position beneath the tumor appears to increase RON and improve local control. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. (Source: Ophthalmology)

Uveal Melanoma and BRCA1/BRCA2 Genes: A Relationship That Needs Further Investigation [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Tue, 29 Nov 2011 05:00:00 +0100

(Source: Journal of Clinical Oncology)

Sclerosis drug could slow eye cancer growth

Pharmaceutical Technology — Tue, 29 Nov 2011 00:00:00 +0100

A drug used to treat amyotrophic lateral sclerosis, a form of motor neurone disease, has been shown to make eye tumours less likely to grow if they spread to other parts of the body, a study conducted at the Washington University School of Medicine i… (Source: Pharmaceutical Technology)

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Drug may slow spread of deadly eye cancer

ScienceDaily Headlines — Mon, 28 Nov 2011 22:12:12 +0100

A drug commonly used to treat seizures appears to make eye tumors less likely to grow if they spread to other parts of the body, according to researchers. (Source: ScienceDaily Headlines)

The switch from pRb/p105 to Rb2/p130 in DNA damage and cellular senescence

Journal of Cellular Physiology — Thu, 24 Nov 2011 01:41:28 +0100

AbstractCellular senescence is a response to genotoxic stress that results in an irreversible cell cycle arrest. Activation of this pathway relies on the activity of the retinoblastoma proteins and proteins of the DNA damage response cascade. Here, we discuss the functional relevance of the switch from pRb/p105 to Rb2/p130 that becomes apparent when cells enter senescent arrest. J. Cell. Physiol. 227: 508–513, 2012. © 2011 Wiley Periodicals, Inc. (Source: Journal of Cellular Physiology)

IVF and retinoblastoma revisited

Fertility and Sterility — Wed, 23 Nov 2011 05:00:00 +0100

Conclusion(s): Examination of retinoblastoma tumors of seven children conceived by IVF or ICSI did not show hypermethylation of the RB1 promoter. This demonstrates that an association between IVF or ICSI and retinoblastoma through this epigenetic mechanism is unlikely. (Source: Fertility and Sterility)

Adjuvant Chemo Prevents Retinoblastoma SpreadAdjuvant Chemo Prevents Retinoblastoma Spread

Medscape Hematology-Oncology Headlines — Mon, 21 Nov 2011 23:17:13 +0100

After enucleation for high-risk retinoblastoma, VEC chemotherapy (vincristine, etoposide, carboplatin) very effectively prevents metastasis, according to a report from the Wills Eye Institute in Philadelphia. Reuters Health Information (Source: Medscape Hematology-Oncology Headlines)

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Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers

Journal of Medical Genetics — Mon, 21 Nov 2011 05:00:00 +0100

Conclusion This study reports a novel hereditary cancer syndrome caused by a germline BAP1 mutation that predisposes patients to UM, lung carcinoma, meningioma, and possibly other cancers. The results indicate that BAP1 is the candidate gene in only a small subset of hereditary UM, suggesting the contribution of other candidate genes. (Source: Journal of Medical Genetics)

Genetic Testing for Eye Tumor Cuts Surveillance Costs (CME/CE)

MedPage Today Ophthalmology — Sat, 19 Nov 2011 15:43:14 +0100

(MedPage Today) -- Genetic testing of children with retinoblastoma and their families greatly reduced unnecessary and expensive clinical surveillance among potentially at-risk family members, a study suggested. (Source: MedPage Today Ophthalmology)

Adjuvant chemo prevents retinoblastoma spread

Modern Medicine — Fri, 18 Nov 2011 05:00:00 +0100

NEW YORK (Reuters Health) - After enucleation for high-risk retinoblastoma, VEC chemotherapy (vincristine, etoposide, carboplatin) very effectively prevents metastasis, according to a report from the Wills Eye Institute in Philadelphia. (Source: Modern Medicine)

Access to the ophthalmic artery by retrograde approach through the posterior communicating artery for intra-arterial chemotherapy of retinoblastoma

Neuroradiology — Thu, 17 Nov 2011 07:00:02 +0100

We report our experience of using a retrograde approach through the posterior communicating artery that allows a more direct angle of access to the origin of the ophthalmic artery. Content Type Journal ArticleCategory Interventional NeuroradiologyPages 1-4DOI 10.1007/s00234-011-0978-4Authors Chi-Tuan Pham, Department of Interventional Neuroradiology, Fondation Rothschild Hospital, 25 rue Manin, Paris, FranceRaphaël Blanc, Department of Interventional Neuroradiology, Fondation Rothschild Hospital, 25 rue Manin, Paris, FranceLivia Lumbroso-Le Rouic, Department of Ocular Oncology, Institut Curie, 26 rue d’Ulm, Paris, FranceSilvia Pistocchi, Department of Interventional Neuroradiology, Fondation Rothschild Hospital, 25 rue Manin, Paris, FranceBruno Bartolini, Department of Intervent...

VEGF expression in residual tumor cells in orbital retinoblastoma (IRSS stage III) treated with NACT: A prospective study

Pediatric Blood and Cancer — Wed, 16 Nov 2011 16:39:46 +0100

AbstractWe prospectively evaluated vascular endothelial growth factor (VEGF) expression by immunohistochemistry in 22 consecutive IRSS stage III retinoblastoma patients who underwent enucleation after neoadjuvant chemotherapy (NACT). Positive VEGF expression was observed in 6/22 (27.3%) patients. VEGF expression was associated with local progression on MRI prior to enucleation (P = 0.004), pathological scleral (P = 0.023), and extra‐scleral tumor extension (P = 0.009). EFS for VEGF positive and negative patients was 0% and 56.25%, respectively (P = 0.0002). OS for VEGF positive patients was 33.33% and 54.69% for VEGF negative patients (P = 0.207). Thus, VEGF in residual tumor cells post‐NACT may represent poor response to NACT, potential for local invasion, and infe...

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Retinoblastoma Care Should Include Genetic Evaluation

Health News from Medical News Today — Wed, 16 Nov 2011 08:00:00 +0100

Results of a study by Baylor College of Medicine physicians underscore the important role that clinical genetic evaluation can have in the management plan of patients with retinoblastoma, a childhood cancer of the eye. The report documents the success of using a multi-disciplinary team approach to achieving the goal of providing genetic evaluation and testing of all retinoblastoma patients at Texas Children's Cancer Center over an eight-year period. Results were published in the Archives of Ophthalmology... (Source: Health News from Medical News Today)

Phase 1, Dose-escalation Trial of the Oral Cyclin-dependent Kinase 4/6 Inhibitor PD 0332991, Administered Using a 21-day Schedule in Patients with Advanced Cancer.

Clinical Cancer Research — Wed, 16 Nov 2011 05:00:00 +0100

CONCLUSIONS: PD 0332991 warrants phase 2 testing at 125 mg QD, at which dose neutropenia was the sole significant toxicity. PMID: 22090362 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Proton beam therapy for the treatment of uveal melanoma in Scotland

British Journal of Ophthalmology — Wed, 16 Nov 2011 05:00:00 +0100

Conclusion PBT is reserved for the treatment of mainly medium-sized and large-sized uveal melanomas in Scotland. The eye retention and disease-specific survival rates confirm its suitability as an eye-preserving primary treatment in these patients. It is evident that PBT is a conservative treatment option for uveal melanoma, including those of larger size. (Source: British Journal of Ophthalmology)

Intra-arterial Chemotherapy for Retinoblastoma: Report No. 1, Control of Retinal Tumors, Subretinal Seeds, and Vitreous Seeds [Clinical Sciences]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

Conclusions Of 12 eyes managed with IAC as primary treatment, globe salvage was achieved in 67%. Eyes classified as group C or D showed 100% globe salvage, whereas group E had 33% salvage. Of 4 eyes managed with IAC as secondary treatment, globe salvage was achieved in 50%. (Source: Archives of Opthalmology)

Intra-arterial Chemotherapy for Retinoblastoma: Report No. 2, Treatment Complications [Clinical Sciences]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

Conclusions Treatment with IAC for retinoblastoma can lead to mild and severe short-term ocular complications, including eyelid edema as well as potentially blinding vascular obstruction. This procedure should be used with caution. (Source: Archives of Opthalmology)

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Histopathologic Observations After Intra-arterial Chemotherapy for Retinoblastoma [Clinical Sciences]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

Conclusion Retinoblastoma can be controlled with IAC, but histopathology of enucleated eyes reveals that ocular complications including thromboembolic events can occur. (Source: Archives of Opthalmology)

Postenucleation Adjuvant Chemotherapy With Vincristine, Etoposide, and Carboplatin for the Treatment of High-Risk Retinoblastoma [Clinical Sciences]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

Conclusions Retinoblastoma with invasion into the postlaminar optic nerve and/or posterior uvea is at high risk for metastasis and death. In this study, postenucleation chemotherapy using vincristine, etoposide, and carboplatin was effective in preventing metastasis in every case (100%). (Source: Archives of Opthalmology)

Outcomes of Integrating Genetics in Management of Patients With Retinoblastoma [Clinical Sciences]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

Conclusions Our study emphasizes that genetics can be incorporated into the management plan of all retinoblastoma patients using a team approach to ensure timely evaluations and appropriate counseling. Genetic evaluations improved risk prediction for patients and family members as well as prevented overutilization of clinical screening tests, which had potential morbidity for relatives documented to not carry an RB1 mutation. (Source: Archives of Opthalmology)

Intra-arterial Chemotherapy for Advanced Retinoblastoma: Is the Time Right for a Prospective Clinical Trial? [Editorial]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

(Source: Archives of Opthalmology)

Chemosurgery for Retinoblastoma: What We Know After 5 Years [Editorial]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

(Source: Archives of Opthalmology)

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Vitelliform Retinopathy in Metastatic Cutaneous Melanoma With Choroidal Involvement [Research Letters]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

(Source: Archives of Opthalmology)

Cutaneous Halo Nevi Following Plaque Radiotherapy for Uveal Melanoma [Research Letters]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

(Source: Archives of Opthalmology)

Histopathologic, Immunohistochemical, Ultrastructural, and Cytogenetic Analysis of Oncocytic Uveal Melanoma [Research Letters]

Archives of Opthalmology — Mon, 14 Nov 2011 05:00:00 +0100

(Source: Archives of Opthalmology)

Genetic evaluation should be part of retinoblastoma care

Baylor College of Medicine News — Mon, 14 Nov 2011 05:00:00 +0100

(Source: Baylor College of Medicine News)

How Good Are Hearing and Vision Screening Tests in Children?

PediatricEducation.org — Mon, 14 Nov 2011 00:28:22 +0100

Discussion Sensory problems in children like any problem should try to be identified as early as possible so effective treatment plans can be carried out. Hearing About 1-4 children/1000 newborn infants have hearing loss or about 8-16,000 infants/year in the US. Before universal hearing screening the average age for detection was 2 1/2 -3 years of age. In 2010, an evaluation of the universal newborn hearing screening programs found that about 92% of infants were screened before discharge with 4% failing the before discharge screening. Unfortanately only 2% were referred for a diagnostic evaluation. The authors cite multiple barriers to universal screening and followup. Types of hearing testing for screening includes evolked otoacoustic emission testing, auditory brainstem response or bo...

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Differences in uveal melanomas between men and women from the British Isles

Eye — Fri, 11 Nov 2011 08:00:00 +0100

Authors: B E Damato & S E Coupland (Source: Eye)

Retrobulbar primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus)

Journal of Medical Primatology — Thu, 10 Nov 2011 05:00:00 +0100

Conclusions This is the first reported case for the retrobulbar location of primitive neuroectodermal tumor in non‐human primates. (Source: Journal of Medical Primatology)

Arabidopsis Homologs of Retinoblastoma-Associated Protein 46/48 Associate with a Histone Deacetylase to Act Redundantly in Chromatin Silencing

PLoS Genetics — Thu, 10 Nov 2011 05:00:00 +0100

by Xiaofeng Gu, Danhua Jiang, Wannian Yang, Yannick Jacob, Scott D. Michaels, Yuehui He RNA molecules such as small-interfering RNAs (siRNAs) and antisense RNAs (asRNAs) trigger chromatin silencing of target loci. In the model plant Arabidopsis, RNA–triggered chromatin silencing involves repressive histone modifications such as histone deacetylation, histone H3 lysine-9 methylation, and H3 lysine-27 monomethylation. Here, we report that two Arabidopsis homologs of the human histone-binding proteins Retinoblastoma-Associated Protein 46/48 (RbAp46/48), known as MSI4 (or FVE) and MSI5, function in partial redundancy in chromatin silencing of various loci targeted by siRNAs or asRNAs. We show that MSI5 acts in partial redundancy with FVE to silence FLOWERING LOCUS C (FLC), which is a cr...

How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

The British Journal of Nutrition — Wed, 09 Nov 2011 05:00:00 +0100

In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation. PMID: 22067725 [PubMed - as supplied by publisher] (Source: The British Journal of Nutrition)

Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma.

Clinical Cancer Research — Mon, 07 Nov 2011 05:00:00 +0100

Authors: Carbone M, Yang H Abstract Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and NF-kB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. PI3K, AKT and the downstream mTOR are involved in cell growth and survival and are often found to be activated in mesothelioma. p16INK4a and p14ARF are frequently inactivated in human mesothelioma, and approximately 50% of mesotheliomas contain NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except, possibly, for a small subset of patients that have benefit from certain therapies such as ra...

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Working without kinase activity: phosphotransfer-independent functions of extracellular signal-regulated kinases.

Science Signaling — Sat, 05 Nov 2011 01:35:15 +0100

Authors: Rodríguez J, Crespo P Abstract The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1 (ERK1) and ERK2 play well-characterized roles in the regulation of key cellular processes, such as proliferation, differentiation, and survival, by acting as serine and threonine kinases in the phosphorylation of ~200 substrates that are distributed in different subcellular localizations. However, over the past few years, evidence has mounted that indicates that the mechanism of action of ERK1 and ERK2 may extend beyond their role as canonical kinases. For example, proteins such as poly(ADP-ribose) polymerase 1, topoisomerase II, and MAPK phosphatase 3 (MKP-3) are activated by a direct interaction with ERK2 that does not involve any phosphotransfer activity...

Collaborative Ocular Melanoma Study randomized trial of I-125 brachytherapy.

Clinical Trials — Thu, 03 Nov 2011 22:10:03 +0100

CONCLUSIONS: The multidisciplinary COMS Group not only successfully conducted a randomized trial that answered the primary study questions but also has contributed to clinical and epidemiologic knowledge of choroidal melanoma through numerous publications. As a consequence of the COMS, a standard approach to I-125 brachytherapy for treatment of choroidal melanoma became widely available to affected patients. PMID: 22013172 [PubMed - in process] (Source: Clinical Trials)

Pesticide exposure in farming and forestry and the risk of uveal melanoma

Cancer Causes and Control — Thu, 03 Nov 2011 16:54:38 +0100

Conclusions Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures. Content Type Journal ArticleCategory Original paperPages 1-11DOI 10.1007/s10552-011-9863-zAuthors Thomas Behrens, Bremen Institute for Prevention Research and Social Medicine, Achterstraße 30, 28359 Bremen, GermanyElsebeth Lynge, Institute of Public Health, University of Copenhagen, Copenhagen, DenmarkIan Cree, Institute of Ophthalmology, University College London, London, UKJean-Michel Lutz, National Institute for Cancer Epidemiology and Registration (NICER), University of Zurich, Zurich, SwitzerlandMikael Eriksson, Department of Oncology, University Hospital, Lund, SwedenPasc...

Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results.

The British Journal of Ophthalmology — Thu, 03 Nov 2011 04:00:00 +0100

ConclusionUnlike radiation or systemic chemotherapy, intra-arterial chemotherapy can usually prevent the need for enucleation in naive eyes with advanced intraocular retinoblastoma with seeding-especially if the seeding is subretinal. Treatment appears to be less effective in previously treated eyes when subretinal seeding is present (50% at 2 years), but may be more effective in eyes that failed to respond to previous systemic chemotherapy and have only vitreous seeding. PMID: 22053101 [PubMed - as supplied by publisher] (Source: The British Journal of Ophthalmology)

Regulation of Retinoblastoma Protein (Rb) by p21 Is Critical for Adaptation to Massive Small Bowel Resection

Journal of Gastrointestinal Surgery — Tue, 01 Nov 2011 05:53:23 +0100

Conclusion Rb is specifically required for resection-induced adaptation. Restoration of adaptation in p21-null mice by lowering Rb expression suggests a crucial mechanistic role for Rb in the regulation of intestinal adaptation by p21. Content Type Journal ArticleCategory 2011 SSAT Plenary PresentationPages 1-8DOI 10.1007/s11605-011-1747-8Authors Jennifer A. Leinicke, Division of Pediatric Surgery, St. Louis Children’s Hospital, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USAShannon Longshore, Division of Pediatric Surgery, St. Louis Children’s Hospital, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, USADerek Wakeman, Division of Pediatric Surgery, St. Louis Children’...

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Uveal melanoma: diagnostic features.

Monographs in Clinical Cytology — Tue, 01 Nov 2011 04:56:06 +0100

Authors: Biscotti CV, Singh AD PMID: 22024583 [PubMed - in process] (Source: Monographs in Clinical Cytology)

Uveal melanoma: prognostication.

Monographs in Clinical Cytology — Tue, 01 Nov 2011 04:55:56 +0100

Authors: Turell ME, Tubbs RR, Biscotti CV, Singh AD PMID: 22024584 [PubMed - in process] (Source: Monographs in Clinical Cytology)

Cyclooxygenase‐2 expression in the normal human eye and its expression pattern in selected eye tumours

Acta Ophthalmologica — Tue, 01 Nov 2011 04:00:00 +0100

Conclusion: Cyclooxygenase‐2 is constitutively expressed in normal human eyes. The expression of COX‐2 is much lower in selected eye tumours involving COX‐2 expressing cells. (Source: Acta Ophthalmologica)

Retinoblastoma in a Child After Normal Autorefraction and Traditional Vision Screening

PEDIATRICS — Tue, 01 Nov 2011 04:00:00 +0100

Retinoblastoma is an ocular malignancy that can put a patient's sight and, in some instances, life at risk. Here we report the case of a 2-year-old child who presented to her pediatrician with a 2-week history of left-sided leukocoria caused by retinoblastoma. Results of traditional office-based vision screening and automated vision screening, which often identify but are not specifically designed to detect rare diseases such as retinoblastoma, had been normal in the antecedent 7 months. She underwent enucleation of the left eye and has done well postoperatively. This case highlights the importance of assessing ocular media clarity by using red-reflex testing at multiple intervals during the preschool years, particularly in light of the recently published US Preventive Services Task Force ...

Erratum.

Archives of Pathology and Laboratory Medicine — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Abstract An article by Suryawanshi et al that appears in the August 2011 issue of the Archives (Suryawanshi P, Ramadwar M, Dikshit R, et al. A Study of Pathologic Risk Factors in Postchemoreduced, Enucleated Specimens of Advanced Retinoblastomas in a Developing Country. Arch Pathol Lab Med. 2011;135[8]:1017-1023 ) lists an incorrect e-mail address for the corresponding author. The correct e-mail address for Dr. Viswanathan is drseetha.v@gmail.com . PMID: 22032558 [PubMed - in process] (Source: Archives of Pathology and Laboratory Medicine)

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KIF20A and Its Gene Product MKlp2 Are Increased During Hepatocyte Proliferation and Hepatocarcinogenesis.

The American Journal of Pathology — Tue, 01 Nov 2011 04:00:00 +0100

We report herein that MKlp2 transiently accumulates in vivo during mouse liver regeneration after partial hepatectomy and is strongly overexpressed in preneoplastic and neoplastic mouse liver. In vitro in mitogen-stimulated primary hepatocytes, MKlp2 accumulated in the nucleus during the G2 phase of the cell cycle coincident with the mitotic kinase Aurora B. Human hepatoma cell lines exhibited high levels of MKlp2; however, it was undetectable in normal human hepatocytes. RNAi-mediated MKlp2 knockdown in hepatoma cells induced polyploidization consistent with its essential function in promoting cytokinesis and inhibited cell proliferation without inducing apoptosis. KIF20A mRNA was strongly accumulated in a large series of human hepatocellular carcinomas, with the highest expression observ...

Right Atrial B‐Cell Lymphoma in a Patient with Ocular Melanoma

Journal of Cardiac Surgery — Tue, 01 Nov 2011 04:00:00 +0100

We report the case of a healthy 53‐year‐old male who originally presented with blurred vision secondary to a right intraocular mass. Enucleation of the eye confirmed a ciliary body melanoma and, upon further investigation, the patient was discovered to have a mass in the right atrium suspicious for a myxoma. However, resection of the atrial mass revealed a low‐grade B‐cell PCL. The occurrence of PCL in an immunocompetent patient being investigated for a visceral malignancy makes this a highly unusual presentation of a rare neoplasm. (J Card Surg 2011;26:625‐628) (Source: Journal of Cardiac Surgery)

Gene Expression Reveals Metastatic Risk in Uveal MelanomaGene Expression Reveals Metastatic Risk in Uveal Melanoma

Medscape Today Headlines — Mon, 31 Oct 2011 20:47:31 +0100

Medscape Medical News (Source: Medscape Today Headlines)

Uveal Melanoma Cell Lines Contain Stem-Like Cells That Self-Renew, Produce Differentiated Progeny, and Survive Chemotherapy [Biochemistry and Molecular Biology]

Investigative Ophthalmology — Mon, 31 Oct 2011 04:00:00 +0100

Conclusions. These data suggest the presence in UM cell lines, of a CSC-like subpopulation with enhanced self-renewal and proliferative capabilities that could more appropriately model therapeutic efficacy. (Source: Investigative Ophthalmology)

Clinical Survey of 3680 Iris Tumors Based on Patient Age at Presentation

Ophthalmology — Mon, 31 Oct 2011 04:00:00 +0100

Objective: To report the spectrum of iris lesions based on patient age at presentation. Design: Retrospective, nonrandomized, single-center case series. Participants: We included 3680 iris tumors in 3451 patients. Methods: Chart review. Main Outcome Measures: Diagnostic category based on age. Results: The mean age at presentation was 48 years and there were 449 (12%) tumors in children (≤20 years), 788 (21%) in young adults (21–40 years), 1308 (36%) in mid adults (41–60 years), and 1135 (31%) in senior adults (>60 years). Of 3680 tumors, the diagnostic category was cystic (n = 768; 21%) or solid (n = 2912; 79%). The cystic tumors originated from iris pigment epithelium (IPE; n = 672; 18%) or iris stroma (n = 96; 3%). The solid tumors included melanocytic (n = 2510; 68%) an...

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A Novel MLL5 Isoform That Is Essential to Activate E6 and E7 Transcription in HPV16/18-Associated Cervical Cancers

Cancer Research — Sun, 30 Oct 2011 04:00:00 +0100

In this study, we defined a novel isoform of the mixed lineage leukemia 5 gene (MLL5β) as a specific and critical regulator of E6 and E7 transcription in cervical carcinoma cells. MLL5β is present in HPV16/18-positive cells including human primary cervical carcinoma specimens. Interaction of MLL5β with the AP-1–binding site at the distal region of the HPV18 long control region led to activation of E6/E7 transcription. Conversely, RNA interference–mediated knockdown of MLL5β downregulated both E6 and E7 expression. MLL5β downregulation was sufficient to restore p53 protein levels and reduce Rb phosphorylation, thereby reactivating apoptosis and cell-cycle checkpoints. By defining this novel MLL5β isoform and its specific critical role in activating E6/E7 gene transcription in HPV1...

Lentiviral Vector-Mediated PAX6 Overexpression Promotes Growth and Inhibits Apoptosis of Human Retinoblastoma Cells [Retinal Cell Biology]

Investigative Ophthalmology — Fri, 28 Oct 2011 04:00:00 +0100

Conclusions. Lentiviral vector-mediated overexpression of PAX6 in human retinoblastoma cells was associated with increased cell proliferation parallel to a reduced caspase-3–dependent apoptotic rate and a change in the p53 regulated cell cycle. PAX6 may be further explored for the diagnosis of and therapy for retinoblastomas. (Source: Investigative Ophthalmology)

Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma.

Clinical Cancer Research — Fri, 28 Oct 2011 04:00:00 +0100

CONCLUSIONS: These findings suggest that HDAC inhibitors may have therapeutic potential for inducing differentiation and prolonged dormancy of micrometastatic disease in UM. PMID: 22038994 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Neoplasm Mimics of Rheumatologic Presentations: Sialadenitis, Ocular Masquerade Syndromes, Retroperitoneal Fibrosis, and Regional Pain Syndromes

Rheumatic Disease Clinics of North America — Fri, 28 Oct 2011 04:00:00 +0100

This article reviews a group of miscellaneous malignant conditions that may mimic rheumatologic diseases. Primary salivary gland cancer as well as lymphoproliferative conditions such as lymphoma and IgG4 related syndromes should be considered when evaluating a patient with sialadenosis. Primary intraocular lymphoma and melanoma in adults as well as leukemia and retinoblastoma in children may present as idiopathic ocular inflammation and require a high index of suspicion. Retroperitoneal fibrosis may mimic lymphoma or a solid malignancy and poses diagnostic challenges. Regional pain syndromes, such as complex regional pain and carpal tunnel syndromes, may be a manifestation of cancer and amyloidosis respectively. Awareness of these rare mimics may serve in guiding diagnostic investigations....

Intense Protocol With High-Dose Chemotherapy Saves EyesIntense Protocol With High-Dose Chemotherapy Saves Eyes

Medscape Today Headlines — Thu, 27 Oct 2011 23:09:49 +0100

Intensive high-dose chemotherapy and periocular carboplatin achieved high rates of vision salvage and complete regression in children with retinoblastoma with vitreous seeds. Medscape Medical News (Source: Medscape Today Headlines)

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Current Concepts in Uveal Melanoma

Karger Publishers — Wed, 26 Oct 2011 10:18:58 +0100

ISBN: 978-3-8055-9790-6 (Source: Karger Publishers)

Caveolin-2 is a negative regulator of anti-proliferative function and signaling of transforming growth factor-{beta} in endothelial cells

AJP: Cell Physiology — Wed, 26 Oct 2011 04:00:00 +0100

Using a combination of wild-type (WT) and caveolin-2 (Cav-2) knockout along with retroviral reexpression approaches, we provide the evidence for the negative role of Cav-2 in regulating anti-proliferative function and signaling of transforming growth factor β (TGF-β) in endothelial cells (ECs). Although, TGF-β had a modest inhibitory effect on WT ECs, it profoundly inhibited proliferation of Cav-2 knockout ECs. To confirm the specificity of the observed difference in response to TGF-β, we have stably reexpressed Cav-2 in Cav-2 knockout ECs using a retroviral approach. Similar to WT ECs, the anti-proliferative effect of TGF-β was dramatically reduced in the Cav-2 reexpressing ECs. The reduced anti-proliferative effect of TGF-β in Cav-2-positive cells was eviden...

Cellular senescence and tumor suppressor gene p16

International Journal of Cancer — Tue, 25 Oct 2011 04:00:00 +0100

AbstractCellular senescence is an irreversible arrest of cell growth. Biochemical and morphological changes occur during cellular senescence, including the formation of a unique cellular morphology such as flattened cytoplasm. Function of mitochondria, endoplasmic reticulum and lysosomes are affected resulting in the inhibition of lysosomal and proteosomal pathways. Cellular senescence can be triggered by a number of factors including, aging, DNA damage, oncogene activation and oxidative stress. While the molecular mechanism of senescence involves p16 and p53 tumor suppressor genes and telomere shortening, this review is focused on the mechanism of p16 control. The p16 mediated senescence acts through the retinoblastoma (Rb) pathway inhibiting the action of the cyclin dependant kinases lea...

The incidence and distribution of retinoblastoma in Kenya.

The British Journal of Ophthalmology — Tue, 25 Oct 2011 04:00:00 +0100

Authors: Nyamori JM, Kimani K, Njuguna MW, Dimaras H PMID: 22028473 [PubMed - as supplied by publisher] (Source: The British Journal of Ophthalmology)

Sector (Partial) Oculo(dermal) Melanocytosis in 89 Eyes

Ophthalmology — Mon, 24 Oct 2011 04:00:00 +0100

Conclusions: Ocular melanocytosis can be sectoral (partial), affecting only a mean of 5 to 6 clock hours of the uvea and can manifest melanoma within the melanocytosis region. There were no specific features of melanocytosis statistically related to the presence of melanoma.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. (Source: Ophthalmology)

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MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts

Journal of Molecular and Cellular Cardiology — Mon, 24 Oct 2011 04:00:00 +0100

In conclusion, we demonstrate a differentially regulated cohort of microRNAs that predicts differences in cellular proliferation in CPCs during postnatal development and target microRNAs that are involved in this transition. Our study provides new insights that may enhance the utilization of adult CPCs for regenerative therapy of the injured myocardium.Highlights: ► MicroRNA profiles in cardiac progenitor cells (CPCs) are distinct developmentally. ► The predicted protein targets are predominantly involved in cellular proliferation. ► The proliferative capacity of neonatal CPCs is higher than adult CPCs. ► Over-expression of miR-17-92 increases the proliferation in adult CPCs. ► A cohort of microRNAs may predict differences in cellular proliferation in CPCs. (Source: Journal of Mo...

Evidence for the presence of high risk human papillomavirus in retinoblastoma tissue from nonfamilial retinoblastoma in developing countries

Pediatric Blood and Cancer — Sat, 22 Oct 2011 00:35:27 +0100

ConclusionsOur study lends support to the hypothesis that infection of HPV‐16/‐18 may play an important role in the development of nonfamilial form of RB in children in India. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Prevalence of ocular and oculodermal melanocytosis in Spanish population with uveal melanoma

Eye — Fri, 21 Oct 2011 07:00:00 +0100

Authors: E Carreño, M A Saornil, C Garcia-Alvarez, F Lopez-Lara, J M De Frutos-Baraja & A Almaraz (Source: Eye)

Lack of evidence for a link between latanoprost use and malignant melanoma: an analysis of safety databases and a review of the literature

British Journal of Ophthalmology — Fri, 21 Oct 2011 04:00:00 +0100

Conclusion There is no evidence at present that establishes a link between latanoprost use and either ocular or cutaneous melanoma. (Source: British Journal of Ophthalmology)

Association of high metabolic activity measured by positron emission tomography imaging with poor prognosis of choroidal melanoma

British Journal of Ophthalmology — Fri, 21 Oct 2011 04:00:00 +0100

Conclusion Metabolic activity by PET imaging significantly predicted the survival of patients with choroidal melanoma. (Source: British Journal of Ophthalmology)

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Retinoblastoma in patients with regressed retinopathy of prematurity

Indian Journal of Ophthalmology — Wed, 19 Oct 2011 04:00:00 +0100

We report two patients (1 and 2) with regressed ROP who later presented with retinoblastoma (RB). To the best of our knowledge, there is only one such report in the literature so far. Two unrelated patients 1 and 2, born at 32 weeks gestation were screened for ROP at 34 weeks gestation. This showed Zone II Stage II ROP which regressed by 38 weeks of gestation on follow-up. Both patients were lost to follow-up by 40 weeks of gestation. They presented at four years of age with white reflex in the eye. Patient 1 was found to have unilateral and patient 2 bilateral RB. The occurrence of RB in these patients with regressed ROP is probably coincidental. (Source: Indian Journal of Ophthalmology)

Genome-Wide Analyses Identify Recurrent Amplifications of Receptor Tyrosine Kinases and Cell-Cycle Regulatory Genes in Diffuse Intrinsic Pontine Glioma [Pediatric Oncology]

Journal of Clinical Oncology — Tue, 18 Oct 2011 04:00:00 +0100

Conclusion DIPGs comprise a molecularly related but distinct subgroup of pediatric gliomas. Genomic studies suggest that targeted inhibition of receptor tyrosine kinases and RB regulatory proteins may be useful therapies for DIPG. (Source: Journal of Clinical Oncology)

Early satellite Metastatic Uveal Melanoma to The Lower Eyelid - The First Report.

Orbit — Tue, 18 Oct 2011 04:00:00 +0100

Conclusion: The paper is, according to our knowledge, the first documented case of an early satellite metastatic uveal melanoma to the lower eyelid in the patient with no evidence of further metastases. PMID: 22007917 [PubMed - as supplied by publisher] (Source: Orbit)

High‐throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide‐3‐kinase and other oncogenes

Cancer — Mon, 17 Oct 2011 04:00:00 +0100

CONCLUSIONS:In this largest mutational profiling of osteosarcoma to date, the authors identified for the first time several mutations involving the PI3K pathway, adding osteosarcoma to the growing list of malignancies with PI3K mutations. In addition, they initiated a mutational map detailing DNA sequence changes across a variety of osteosarcoma subtypes and offered new candidates for therapeutic targeting. Cancer 2011. © 2011 American Cancer Society. (Source: Cancer)

Analysis of aqueous humor proteins in patients with retinoblastoma

Clinical and Experimental Ophthalmology — Mon, 17 Oct 2011 04:00:00 +0100

Conclusion: This study represents a preliminary step towards a more accurate 2DE pattern, which will be combined with mass spectrometry analysis to clarify the potential role of specific proteins in tumor development and progression; although this results suggest that aqueous humor protein pattern in retinoblastoma is characteristic, several aspects of the study are still under investigation. (Source: Clinical and Experimental Ophthalmology)

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Analysis of aqueous humour proteins in patients with retinoblastoma

Clinical and Experimental Ophthalmology — Mon, 17 Oct 2011 04:00:00 +0100

Conclusion: This study represents a preliminary step towards a more accurate two dimensional electrophoresis (2DE) pattern, which will be combined with mass spectrometry analysis to clarify the potential role of specific proteins in tumour development and progression; although these results suggest that aqueous humour protein pattern in retinoblastoma is characteristic, several aspects of the study are still under investigation. (Source: Clinical and Experimental Ophthalmology)

Proliferation versus Elastogenesis [Glycobiology and Extracellular Matrices]

Journal of Biological Chemistry — Fri, 14 Oct 2011 04:00:00 +0100

The mechanism that leads to the inverse relationship between heightened cellular proliferation and the cessation of elastic fibers production, observed during formation of the arterial occlusions and dermal scars, is not fully understood. Because the retinoblastoma protein (Rb), responsible for cell cycle initiation, has also been implicated in insulin-like growth factor-I-mediated signaling stimulating elastin gene activation, we explored whether differential phosphorylation of Rb by various cyclin·cyclin-dependent kinase complexes would be responsible for promoting either elastogenic or pro-proliferative signals. We first tested cultures of dermal fibroblasts derived from Costello syndrome patients, in which heightened proliferation driven by mutated oncogenic H-Ras coincides with inhib...

Oral contraceptive and progestin-only use correlates to tissue tumor marker expression in women with cervical intraepithelial neoplasia

Contraception — Thu, 13 Oct 2011 04:00:00 +0100

Conclusion: The study showed molecular alterations, which, in general, have not been studied previously in COC users and have never been studied in progestogen-only users. These biological events might be involved in epidemiological correlations found between hormonal contraceptive use and cervical neoplasms. (Source: Contraception)

Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival

Clinical and Experimental Metastasis — Sat, 08 Oct 2011 15:44:20 +0100