Neovascular glaucoma caused by small-cell lung cancer iris metastasis: A case presentation.

Small-cell lung cancer may directly affect the eye by metastatic proliferation or indirectly by paraneoplastic syndromes. The choroid is the most common site for uveal metastasis (90%); however, the iris can be involved in a smaller proportion of cases (incidence <10%). Blurred vision, pain, redness, photophobia, glaucoma, hyphema and visual field defects can arise from this metastatic involvement. The median survival time for patients with iris metastasis is reported to be 4 months. Secondary glaucoma can be managed with topical and oral treatment, transscleral cyclophotocoagulation, laser trabeculoplasty, anti-VEGF, Minimally Invasive Glaucoma Surgery (MIGS), filtering surgery, shunting surgery or enucleation. A case of primary small-cell lung cancer with iris metastasis is presented. The metastases produced an angle-closure glaucoma, which was refractory to topical treatment. Local radiotherapy was administered, obtaining a good local response.

Association between maxillary sinus pathology and odontogenic lesions in patients evaluated by cone beam computed tomography. A systematic review and meta-analysis.

BACKGROUND: A study is made of the association between maxillary sinus pathology and odontogenic lesions in patients evaluated with cone beam computed tomography. MATERIAL AND METHODS: A literature search was made in five databases and OpenGrey. Methodological assessment was carried out using the Newcastle-Ottawa tool for observational studies. The random-effects model was used for the meta-analysis. RESULTS: Twenty-one studies were included in the qualitative review and 6 in the meta-analysis. Most presented moderate or low risk of bias. The periodontal disease showed to be associated with the thickening of the sinus membrane (TSM). Mucous retention cysts and opacities were reported in few studies. The presence of periapical lesions (PALs) was significantly associated to TSM (OR=2.43 (95%CI:1.71-3.46); I2=34.5%) and to odontogenic maxillary sinusitis (OMS) (OR=1.77 (95%CI: 1.20-2.61); I2=35.5%). CONCLUSIONS: The presence of PALs increases the probability of TSM and OMS up to 2.4-fold and 1.7-fold respectively. The risk differences suggests that about 58 and 37 of out every 100 maxillary sinuses having antral teeth with PALs are associated with an increased risk TSM and OMS respectively. The meta-evidence obtained in this study was of moderate certainty, and although the magnitude of the observed associations may vary, their direction in favor sinus disorders appearance, would not change as a result.

Li-Fraumeni syndrome heterogeneity.

Clinical variability is commonly seen in Li-Fraumeni syndrome. Phenotypic heterogeneity is present among different families affected by the same pathogenic variant in TP53 gene and among members of the same family. However, causes of this huge clinical spectrum have not been studied in depth. TP53 type mutation, polymorphic variants in TP53 gene or in TP53-related genes, copy number variations in particular regions, and/or epigenetic deregulation of TP53 expression might be responsible for clinical heterogeneity. In this review, recent advances in the understanding of genetic and epigenetic aspects influencing Li-Fraumeni phenotype are discussed.

Synthesis and biological evaluation as microtubule-active agents of several tetrahydrofuran and spiroacetal derivatives.

The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described. Their degree of cytotoxicity and their interactions with tubulin have been investigated. It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network. Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established.

Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of TMS1 gene hypermethylation in relapse risk in NB patients.

PURPOSE: Most neuroblastoma patients over 18 months of age at diagnosis present disseminated disease. The presence of neuroblastoma cells in bone marrow can be used to evaluate the response to treatment. It is possible that alterations in certain tumour cells might confer a selective advantage over tumour dissemination process, and probably be helpful in the clonal selection of tumour-specific cells that could originate metastasis. METHODS: We performed real-time quantitative PCR to identify the presence of disseminated tumour cells in bone marrow samples, and we used MSP to analyse the methylation profile of 20 genes putatively implied in dissemination. RESULTS: We described epigenetic alterations in the methylated status of certain genes in disseminated tumour cells from bone marrow. Those cases with high rate of hypermethylation showed an increased probability of relapse during or after treatment. We found significantly poor prognosis in event-free survival in cases with hypermethylation of TMS1, MGMT and RARbeta2 genes. CONCLUSION: We could not confirm the presence of a specific methylation profile in disseminated neuroblastoma tumour cells, but a high accumulation of epigenetic events in those cells is associated with a high risk of relapse, independently of MYCN amplification.

Subtelomeric analysis of pediatric astrocytoma: subchromosomal instability is a distinctive feature of pleomorphic xanthoastrocytoma.

Astrocytic neoplasms are genetically heterogeneous; however a low frequency of genomic changes has been found in juvenile pilocytic astrocytoma (PA) in molecular studies. Concerning pleomorphic xanthoastrocytomas (PXA), recent studies have given heterogeneous results for chromosomal alterations. We studied the subtelomeric regions of 19 primary astrocytoma tumors. Results were near normality for the PA group with relative scarcity of chromosomal imbalances, except for the duplication of 3pter in 4/15 and deletion of 21qter in 5/15 of them. In contrast, a specific profile was observed in the 4 PXA tumoral samples. This involved 3pter, 14qter and 19pter duplication and 4qter, 6qter, 9qter, 13cen, 17pter, 18qter and 21qter deletion. Our results indicate that the chromosomal and genetic aberrations in PXAs differed from those typically associated with the diffusely infiltrating astrocytic and oligodendroglial gliomas. These genetic differences would likely contribute to the more favorable behavior of PXAs and may be helpful for molecular differential diagnosis of pediatric cerebral tumors.

Tumour banks in pediatric oncology.

INTRODUCTION: The information offered by the new genomic and proteomic techniques will play a central role in our knowledge of cancer; but it is limited by the lack of available tissue samples. Cancer in children is a sum of infrequent diseases, so tumor banks are support tools for translational research, providing access to a sufficiently large series of samples, which would minimize the asymmetric effect of the diverse origin. MATERIAL AND METHODS: From 2003 a Molecular Pathology Network in Pediatric Solid Tumors Netwoks exists in Spain, and we are a part of it. Our aim was to create a pediatric tumor bank program and consensus documents about its use. RESULTS: Standard Operating Procedures for collection and transport of samples have been created. CONCLUSIONS: Thinking about the fast progress in Molecular Biology and the low frequency in pediatric tumors, it is vital to consider the importance of a bio bank.

Mutation profile of the MYO7A gene in Spanish patients with Usher syndrome type I.

Usher syndrome type I is the most severe form of Usher syndrome. It is an autosomal recessive disorder characterized by profound congenital sensorineural deafness, retinitis pigmentosa, and vestibular abnormalities. Mutations in the myosin VIIA gene (MYO7A) are responsible for Usher syndrome type 1B (USH1B). This gene is thought to bear greatest responsibility for USH1 and, depending on the study, has been reported to account for between 24% and 59% of USH1 cases. In this report a mutation screening of the MYO7A gene was carried out in a series of 48 unrelated USH1 families using single strand conformation polymorphism analysis (SSCP) and direct sequencing of those fragments showed an abnormal electrophoretic pattern. Twenty-five mutations were identified in 23 out of the 48 families studied (47.9%). Twelve of these mutations were novel, including five missense mutations, three premature stop codons, three frameshift, and one putative splice-site mutation. Based on our results we can conclude there is an absence of hot spot mutations in the MYO7A gene and that this gene plays a major role in Usher syndrome.

Minimal residual disease in neuroblastoma: to GAGE or not to GAGE.

We assessed the utility of GAGE gene expression as a marker of minimal residual disease (MRD) in neuroblastoma. The GAGE gene family shows a high degree of homology (>90%), clustering into two subgroups. GAGE-1, -2, and -8 form one subset, almost identical among themselves, while GAGE-3 to -7 constitute the other subset. The entire GAGE family (GAGE-1-8) was studied by RT-PCR followed by Southern blotting to increase both the sensitivity and specificity of the technique. Surprisingly, expression of GAGE was detected in 59% of peripheral blood samples from normal controls (20/35) as well as in a similar proportion from neuroblastoma patients with localized disease (stages 1 and 2). The study of GAGE-1, -2, and -8 with specific primers lowered this percentage to 28% (10/35), of which only two (6%) showed a high level of expression (directly visualized after RT-PCR). We conclude that GAGE genes can show a variable, usually low level of illegitimate expression in normal blood cells, and therefore their use as MRD markers should be taken with caution.

Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome.

Two novel mutations of the ribosomal S6 kinase 2 gene (also known as RSK2) have been identified in two unrelated patients with Coffin-Lowry syndrome. The first mutation consists of a de novo insertion of a 5'-truncated LINE-1 element at position -8 of intron 3, which leads to a skipping of exon 4, leading to a shift of the reading frame and a premature stop codon. The L1 fragment (2800 bp) showed a rearrangement with a small deletion, a partial inversion of the ORF 2, flanked by short direct repeats which duplicate the acceptor splice site. However, cDNA analysis of the patient shows that both sites are apparently not functional. The second family showed the nucleotide change 803T>C in exon 10, resulting in the F268S mutation. This mutation was detected in two monozygotic twin patients and in their mother, who was mildly affected. The patients fulfill the clinical criteria of the syndrome, and therefore the mutation provides further support for the importance of phenylalanine at position 268, which is highly conserved in the protein kinase domain of many serine-threonine protein kinases.