Debates of the European Parliament. Report of Proceedings of 8 March 1982. No. 1-286. 1981-1982 Session. March 1982

Background:Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.Methods:Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set.Results:In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas.Conclusions:Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours

The Scandinavian Sarcoma Group Central Register : 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.Peer reviewe

Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation

The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development

Bone defects following curettage do not necessarily need augmentation: A retrospective study of 146 patients

Background and purpose The natural pattern of bone healing in large bony defects following curettage alone as treatment of benign bone tumors around the knee is not well reported. We analyzed the outcome in 146 patients

Misfolded SOD1 Associated with Motor Neuron Mitochondria Alters Mitochondrial Shape and Distribution Prior to Clinical Onset

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS

Influence of firing conditions and production methods on fracture strength of titanium-based metal ceramic crowns

Objectives: This study evaluated the effect of argon atmosphere compared with vacuum during porcelain firing on the fracture strength of crowns made of porcelain and electron beam melted (EBM) Ti-6Al-4 V, cast commercially pure titanium or milled commercially pure titanium. Methods: Sixty crown copings of c. p. titanium, Ti-6Al-4 V alloy and porcelain were fabricated using three production techniques. The copings were fired either under vacuum or in an argon gas atmosphere. Specimens were subdivided into groups of cast c. p. titanium, milled c. p. titanium and EBM Ti-6Al-4 V which were further subdivided according to firing modes employing either vacuum or argon gas. The 60 specimens were subjected to cyclic preloading and thermocycling, and were then individually loaded until interface fractured. Differences between the group mean values were calculated using the one-way ANOVA and Tukey's range test. Two fractured samples from each group were cut with a diamond blade and examined using SEM and EDS for visualization and chemical composition analysis of the fractured interface. Results: The highest mean fracture strength values, though not significant, were recorded for the groups fired in argon atmosphere, and the lowest mean fracture strength values were recorded for the groups fired in vacuum, with one exception. Comparing the two main groups of firing atmosphere, no significant difference could be documented. SEM and EDS analysis indicated clear differences in composition and structure between the groups included in the study. Conclusions: Firing in argon atmosphere does not significantly improve the fracture strength of porcelain bonded to titanium

Influence of firing conditions and production methods on fracture strength of titanium-based metal ceramic crowns

Objectives: This study evaluated the effect of argon atmosphere compared with vacuum during porcelain firing on the fracture strength of crowns made of porcelain and electron beam melted (EBM) Ti-6Al-4 V, cast commercially pure titanium or milled commercially pure titanium. Methods: Sixty crown copings of c. p. titanium, Ti-6Al-4 V alloy and porcelain were fabricated using three production techniques. The copings were fired either under vacuum or in an argon gas atmosphere. Specimens were subdivided into groups of cast c. p. titanium, milled c. p. titanium and EBM Ti-6Al-4 V which were further subdivided according to firing modes employing either vacuum or argon gas. The 60 specimens were subjected to cyclic preloading and thermocycling, and were then individually loaded until interface fractured. Differences between the group mean values were calculated using the one-way ANOVA and Tukey\u27s range test. Two fractured samples from each group were cut with a diamond blade and examined using SEM and EDS for visualization and chemical composition analysis of the fractured interface. Results: The highest mean fracture strength values, though not significant, were recorded for the groups fired in argon atmosphere, and the lowest mean fracture strength values were recorded for the groups fired in vacuum, with one exception. Comparing the two main groups of firing atmosphere, no significant difference could be documented. SEM and EDS analysis indicated clear differences in composition and structure between the groups included in the study. Conclusions: Firing in argon atmosphere does not significantly improve the fracture strength of porcelain bonded to titanium