TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival.

Acquired chromosomal aberrations play an important role in tumour development and progression. Such genetic alterations occur in a significant proportion of non-small cell lung carcinomas (NSCLCs) and include amplification of 14q13.3, which contains the TTF1 gene. We asked whether TTF1 amplification is associated with increased TTF1 protein expression in NSCLCs, and whether TTF1 is associated with clinicopathological features, including patient survival. We used a FISH assay and quantitative immunohistochemical staining to interrogate a population-based cohort of 538 NSCLCs from Swiss patients for TTF1 amplification and protein expression. We found TTF1 amplification in approximately 13% of adenocarcinomas (ACs) and in approximately 9% of squamous cell carcinomas (SCCs) and TTF1 amplification was associated with increased TTF1 protein expression. High-level TTF1 expression was significantly associated with smaller tumour size, female gender and longer overall survival only among ACs (median survival 82 versus 28 months; p = 0.002). On multivariate analysis, high TTF1 expression was an independent predictor of favourable prognosis in patients with AC [hazard ratio, 0.56 (95% CI 0.38-0.83); p = 0.008]. We conclude that TTF1 amplification is a mechanism of high-level TTF1 expression in a subset of NSCLCs. When expressed at high levels, this routinely used diagnostic marker is also an independent biomarker of favourable prognosis in AC.

Short-term morbidity in transdiaphragmatic cardiophrenic lymph node resection for advanced stage gynecologic cancer.

Ovarian cancer is commonly diagnosed at an advanced stage, with disease involving the upper abdomen. The finding of enlarged cardiophrenic lymph nodes (CPLNs) on pre-operative imaging often indicates the presence of malignant spread to the mediastinum. Surgical resection of CPLN through a transdiaphragmatic approach can help to achieve cytoreduction to no gross residual. A retrospective chart review was conducted on all patients who underwent transdiaphragmatic cardiophrenic lymph node resection from 8/1/11 through 2/1/15. All relevant pre-, intra-, and post-operative characteristics and findings were recorded. A brief description of the surgical technique is included for reference. Eleven patients were identified who had undergone transdiaphragmatic resection of cardiophrenic lymph nodes. Malignancy was identified in 18/21 (86%) of total lymph nodes submitted. The median number of post-operative days was 7. The overall post-operative morbidity associated with CPLN resection was low, with the most common finding being a small pleural effusion present on chest x-ray between POD# 3-5 (55%). Transdiaphragmatic CPLN resection is a feasible procedure with relatively minor short-term post-operative morbidities that can be used to achieve cytoreduction to no gross residual disease.

No evidence for involvement of KCNN3 (hSKCa3) potassium channel gene in familial and isolated cases of schizophrenia.

Several studies have reported in schizophrenia a decrease of age of onset in successive family generations, and this observation is consistent with anticipation. Anticipation is known to result from expansion of CAG repeats in several neurodegenerative disorders. Longer alleles of the KCNN3 gene, which contains a highly polymorphic CAG repeat, and encodes a neuronal small conductance calcium-activated potassium channel, have recently been shown to be over-represented in sporadic cases of schizophrenia. In this report, we tested the hypothesis of an association between longer alleles of CAG repeat in the KCNN3 gene and schizophrenia in 20 families with clinical evidence for anticipation and in 151 unrelated schizophrenic cases. No significant difference in the distributions of allele frequencies was observed between familial cases of schizophrenia and controls, and between unrelated cases and controls. Furthermore, no intergenerational CAG repeat instability was detected in the 20 families. Our results do not support the involvement of the KCNN3 (hSKCa3) gene in the etiology of schizophrenia.

Detection of two new polymorphic sites in the human interleukin-1 beta gene: lack of association with schizophrenia in a French population.

The pathogenesis of schizophrenia might involve abnormal development of the human brain. Interleukin-1 beta is a cytokine implicated in the development of the central nervous system and therefore its gene is a candidate gene in schizophrenia. Polymorphisms within the coding sequence and the 3'UTR of the IL1 beta gene were searched for using PCR-SSCP. Two polymorphisms, 1B-175/1B-173 and 1B-1765/1B-1763 were found in addition to the previously published TaqI site. Furthermore, a mutant was found in codon 106 (exon 5) of the IL1 beta gene located next to the published polymorphism at the TaqI site and abolishing this site. This novel mutation encodes an Asp in place of an Asn and was only observed in one patient in our French population. Association studies were conducted with the polymorphisms 1B-175/1B-173 and TaqI. There was no allelic or genotypic association between either of the two polymorphisms and schizophrenia. In our population, there is no evidence that the IL1 beta gene is involved in schizophrenia.

Localized lasing modes of triangular organic microlasers.

We investigated experimentally the ray-wave correspondence in organic microlasers of various triangular shapes. Triangular billiards are of interest since they are the simplest cases of polygonal billiards and the existence and properties of periodic orbits in triangles are not yet fully understood. The microlasers with symmetric shapes that were investigated exhibited states localized on simple periodic orbits, and their lasing characteristics like spectra and far-field distributions could be well explained by the properties of the periodic orbits. Furthermore, asymmetric triangles that do not feature simple periodic orbits were studied. Their lasing properties were found to be more complicated and could not be explained by periodic orbits.

The human ATP binding cassette gene ABCA13, located on chromosome 7p12.3, encodes a 5058 amino acid protein with an extracellular domain encoded in part by a 4.8-kb conserved exon.

The ABCA subfamily of ATP-binding cassette (ABC) transporters includes eleven members to date. In this study, we describe a new, unusually large gene on chromosome 7p12.3, ABCA13. This gene spans over 450 kb and is split into 62 exons. The predicted ABCA13 protein consists of 5,058 ami- no acid residues making it the largest ABC protein described to date. Like the other ABCA subfamily members, ABCA13 contains a hydrophobic, predicted transmembrane segment at the N-terminus, followed by a large hydrophilic region. In the case of ABCA13, the hydrophilic region is unexpectedly large, more than 3,500 amino acids, encoded by 30 exons, two of which are 4.8 and 1.7 kb in length. These two large exons are adjacent to each other and are conserved in the mouse Abca13 gene. Tissue profiling of the major transcript reveals the highest expression in human trachea, testis, and bone marrow. The expression of the gene was also determined in 60 tumor cell lines and the highest expression was detected in the SR leukemia, SNB-19 CNS tumor and DU-145 prostate tumor cell lines. ABCA13 has high similarity with other ABCA subfamily genes which are associated with human inherited diseases: ABCA1 with the cholesterol transport disorders Tangier disease and familial hypoalphalipoproteinemia, and ABCA4 with several retinal degeneration disorders. The ABCA13 gene maps to chromosome 7p12.3, a region that contains an inherited disorder affecting the pancreas (Shwachman-Diamond syndrome) as well as a locus involved in T-cell tumor invasion and metastasis (INM7), and therefore is a positional candidate for these pathologies.

Comparative analysis of the promoter structure and genomic organization of the human and mouse ABCA7 gene encoding a novel ABCA transporter.

We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass, named ABCA7. As it is the case for other ABCA genes, the predicted protein encoded by ABCA7 is a full symmetric transporter, highly conserved across species. The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors. This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages.