Unusual association of alveolar rhabdomyosarcoma with pancreatic metastasis: emerging role of PET-CT in tumor staging

Pancreatic metastases in childhood cancer have been rarely reported in the radiology literature although ample evidence exists in pathology reports for its occurrence in patients with alveolar rhabdomyosarcomas (RMS). Assess the occurrence of pancreatic metastases in alveolar rhabdomyosarcomas, increase awareness of this association and reassess current staging protocols. Three major oncology centers reviewed their records and imaging examinations. Patients’ history and demographics, primary tumor site and histology, presence of tumor recurrence, and presence and location of other metastases were reviewed. Pancreatic metastases occurred in eight patients with alveolar RMS. Four of these presented at diagnosis and four with disease recurrence. In recurrent disease, the duration between the diagnosis of the primary tumor and pancreatic metastases varied from 8 months to 6 years (mean ± SD: 2.38 ± 2.49 years). In all patients who received PET scans, pancreatic metastases showed a marked FDG-uptake, but had variable detectability with CT. Pancreatic metastases were not associated with certain primary tumor locations or presence of other metastases, mandating an evaluation of the pancreas in all cases of alveolar rhabdomyosarcomas. Radiologists should be sensitized and actively evaluate the pancreas in patients with alveolar RMS. Optimizing CT and PET-CT protocols may increase the diagnostic yield

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

A Study of D0 --> K0(S) K0(S) X Decay Channels

Using data from the FOCUS experiment (FNAL-E831), we report on the decay of $D^0$ mesons into final states containing more than one $K^0_S$. We present evidence for two Cabibbo favored decay modes, $D^0\to K^0_SK^0_S K^- \pi^+$ and $D^0\to K^0_SK^0_S K^+ \pi^-$, and measure their combined branching fraction relative to $D^0\to \bar{K} ^0\pi^+\pi^-$ to be $\frac{\Gamma(D^0\to K^0_SK^0_SK^{\pm}\pi^{\mp})}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0106 $\pm$ 0.0019 $\pm$ 0.0010. Further, we report new measurements of $\frac{\Gamma(D^0\to K^0_SK^0_SK^0_S)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0179 $\pm$ 0.0027 $\pm$ 0.0026, $\frac{\Gamma(D^0\to K^0\bar{K} ^0)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0144 $\pm$ 0.0032 $\pm$ 0.0016, and $\frac{\Gamma(D^0\to K^0_SK^0_S\pi^+\pi^-)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0208 $\pm$ 0.0035 $\pm$ 0.0021 where the first error is statistical and the second is systematic.Comment: 11 pages, 3 figures, typos correcte

Mifamurtide for the treatment of nonmetastatic osteosarcoma

International audienceINTRODUCTION: The standard treatment for osteosarcoma requires both macroscopic surgical wide resection and postoperative multi-drug chemotherapy in neoadjuvant and adjuvant settings. However, the 5-year event-free survival has remained at a plateau of 60-70% of patients with nonmetastatic osteosarcoma for more than 30 years. AREAS COVERED: Mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine; L-MTP-PE) is a new agent. L-MTP-PE is a nonspecific immunomodulator, which is a synthetic analog of a component of bacterial cell walls. L-MTP-PE activates macrophages and monocytes as a potent activator of immune response in addition to standard chemotherapy. It also improves the overall survival from 70 to 78% and results in a one-third reduction in the risk of death from osteosarcoma. This review summarizes the most recent findings about L-MTP-PE and its therapeutic application for nonmetastatic osteosarcoma. EXPERT OPINION: Recently, L-MTP-PE has been approved in Europe for the treatment of nonmetastatic osteosarcoma with chemotherapy. L-MTP-PE in combination with traditional treatment is expected to go mainstream and to be beneficial for patients with osteosarcoma. Information about potential benefit regarding mifamurtide use in the neoadjuvant setting (i.e., before surgery) and/or usefulness of L-MTP-PE in metastatic in relapsed and metastatic osteosarcoma requires analysis of expanded access and/or future clinical trials of L-MTP-PE in high-burden and low-burden situations

Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms

Destabilizing Protein Polymorphisms in the Genetic Background Direct Phenotypic Expression of Mutant SOD1 Toxicity

Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles

The nonmedical use of prescription ADHD medications: results from a national Internet panel

© 2007 Novak et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The great screen anomaly—a new frontier in product discovery through functional metagenomics

Functional metagenomics, the study of the collective genome of a microbial community by expressing it in a foreign host, is an emerging field in biotechnology. Over the past years, the possibility of novel product discovery through metagenomics has developed rapidly. Thus, metagenomics has been heralded as a promising mining strategy of resources for the biotechnological and pharmaceutical industry. However, in spite of innovative work in the field of functional genomics in recent years, yields from function-based metagenomics studies still fall short of producing significant amounts of new products that are valuable for biotechnological processes. Thus, a new set of strategies is required with respect to fostering gene expression in comparison to the traditional work. These new strategies should address a major issue, that is, how to successfully express a set of unknown genes of unknown origin in a foreign host in high throughput. This article is an opinionating review of functional metagenomic screening of natural microbial communities, with a focus on the optimization of new product discovery. It first summarizes current major bottlenecks in functional metagenomics and then provides an overview of the general metagenomic assessment strategies, with a focus on the challenges that are met in the screening for, and selection of, target genes in metagenomic libraries. To identify possible screening limitations, strategies to achieve optimal gene expression are reviewed, examining the molecular events all the way from the transcription level through to the secretion of the target gene product

Measurement of the D+ and Ds+ decays into K+K-K+

We present the first clear observation of the doubly Cabibbo suppressed decay D+ --> K-K+K+ and the first observation of the singly Cabibbo suppressed decay Ds+ --> K-K+K+. These signals have been obtained by analyzing the high statistics sample of photoproduced charm particles of the FOCUS(E831) experiment at Fermilab. We measure the following relative branching ratios: Gamma(D+ --> K-K+K+)/Gamma(D+ --> K-pi+pi+) = (9.49 +/- 2.17(statistical) +/- 0.22(systematic))x10^-4 and Gamma(Ds+ --> K-K+K+)/Gamma(Ds+ --> K-K+pi+) = (8.95 +/- 2.12(statistical) +2.24(syst.) -2.31(syst.))x10^-3