Search

Rhadbomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and is subdivided in the embryonal (ERMS) and alveolar (ARMS) subtypes, the latter being associated with the worst prognosis. We report that sulforaphane (SFN), a broccoli-derived anticancer isothiocyanate, causes dose- and time-dependent growth inhibition and apoptosis in both ERMS and ARMS cells. In ARMS, SFN induced the modulation of expression of crucial genes and proteins: mRNA and protein levels of PAX3-FKHR, MYCN, and MET decreased, while those of p21 and TRAIL-receptor DR5 (but not DR4) increased. Since DR5 expression increased specifically in ARMS, we treated ARMS cells with TRAIL, SFN, or their combination. While ARMS cells (RH30 and RH4) proved to be TRAIL-resistant, SFN restored their sensitivity to TRAIL-induced cell-growth inhibition, leading to a stronger effect in combination with TRAIL. ARMS cells transfected with siDR5 showed that SFN-induced DR5 acts as a key regulator, being directly related to the TRAIL-induced cell-growth inhibition. The in vivo anti-tumor activity of SFN and TRAIL was evaluated in a xenograft murine model of ARMS through microPET. The results showed that the systemic treatment (3 wk) of mice with SFN or TRAIL as single agents only delayed tumor evolution, while the combined treatment of SFN and TRAIL led to tumor elimination. These findings indicate that SFN triggers the apoptotic pathway in both alveolar and embryonal rhabdomyosarcomas and that combined treatment with SFN and TRAIL might be a promising therapy for the aggressive alveolar subtype.

Wegener's granulomatosis is a systemic vasculitis with involvement of primary granulomatous upper and lower respiratory tract, glomerulonephritis and vasculitis of small vessels. The lung disease ranges from asymptomatic pulmonary nodules to pulmonary infiltrates and fulminant alveolar haemorrhage. The prognosis is poor due to kidney and respiratory failure, although the data are changing due to new treatments with glucocorticoids and cyclophosphamide. We report a case with severe lung disease, which after appropriate anamnesis, multiple tests, and optimal sequential action, the patient was diagnosed with Wegener's granulomatosis. This disease has a low incidence in the Emergency Department, where the patient history supported by the appropriate additional provides a diagnostic suspicion. It is important that the Emergency Department has the skills to manage the stability in these patients in order to resolve their symptoms., (Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Pneumonectomy (PNX) in experimental animals leads to a species- and age-dependent compensatory growth of the remaining lung lobes. PNX mimics the loss of functional gas exchange units observed in a number of chronic destructive lung diseases. However, unlike in disease models, this tissue loss is well defined, reproducible and lacks accompanying inflammation. Furthermore, compensatory responses to the tissue loss can be easily quantified. This makes PNX a potentially useful model for the study of the cellular and molecular events which occur during realveolarisation. It may therefore help to get a better understanding of how to manipulate these pathways, in order to promote the generation of new alveolar tissue as therapies for destructive lung diseases. This review will explore the insights that experimental PNX has provided into the physiological factors which promote compensatory lung growth as well as the importance of age and species in the rate and extent of compensation. In addition, more recent studies which are beginning to uncover the key cellular and molecular pathways involved in realveolarisation will be discussed. The potential relevance of experimental pneumonectomy to novel therapeutic strategies which aim to promote lung regeneration will also be highlighted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Tooth extraction is associated with dimensional changes in the alveolar ridge. The aim was to examine the effect of single versus contiguous teeth extractions on the alveolar ridge remodeling., Material and Methods: Five female beagle dogs were randomly divided into three groups on the basis of location (anterior or posterior) and number of teeth extracted - exctraction socket classification: group 1 (one dog): single-tooth extraction; group 2 (two dogs): extraction of two teeth; and group 3 (two dogs): extraction of three teeth in four anterior sites and four posterior sites in both jaws. The dogs were sacrificed after 4 months. Sagittal sectioning of each extraction site was performed and evaluated using microcomputed tomography., Results: Buccolingual or palatal bone loss was observed 4 months after extraction in all three groups. The mean of the alveolar ridge width loss in group 1 (single-tooth extraction) was significantly less than those in groups 2 and 3 (p < .001) (multiple teeth extraction). Three-teeth extraction (group 3) had significantly more alveolar bone loss than two-teeth extraction (group 2) (p < .001). The three-teeth extraction group in the upper and lower showed more obvious resorption on the palatal/lingual side especially in the lower group posterior locations., Conclusion: Contiguous teeth extraction caused significantly more alveolar ridge bone loss as compared with when a single tooth is extracted., (© 2011 Wiley Periodicals, Inc.)

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Despite intergroup clinical trials conducted in Europe and North America, outcomes for high risk patients with this disease have not significantly improved in the last several decades, and survival of metastatic or relapsed disease remains extremely poor. Accrual into new clinical trials is slow and difficult, so in vitro cell-line research and in vivo xenograft models present an attractive alternative for preclinical research for this cancer type. Currently, 30 commonly used human RMS cell lines exist, with differing origins, karyotypes, histologies, and methods of validation. Selecting an appropriate cell line for RMS research has important implications for outcomes. There are also potential pitfalls in using certain cell lines including contamination with murine stromal cells, cross-contamination between cell lines, discordance between the cell line and its associated original tumor, imposter cell lines, and nomenclature errors that result in the circulation of two or more presumed unique cell lines that are actually from the same origin. These pitfalls can be avoided by testing for species-specific isoenzymes, microarray analysis, assays for subtype-specific fusion products, and short tandem repeat analysis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease. Herein we report a case of pulmonary alveolar microlithiasis who was suspected to have the disease on chest X-ray and was confirmed on high resolution CT and transbronchial lung biopsy. These investigations showed characteristic features of pulmonary alveolar microlithiasis with diffuse interstitial pulmonary fibrosis.

The bZIP transcription factor C/EBP beta is important for mammary gland development and its expression is deregulated in human breast cancer. To determine whether C/EBP beta regulates mammary stem cells (MaSCs), we employed two different knockout strategies. Using both a germline and a conditional knockout strategy, we demonstrate that mammosphere formation was significantly decreased in C/EBP beta-deficient mammary epithelial cells (MECs). Functional limiting dilution transplantation assays indicated that the repopulating ability of C/EBP beta-deleted MECs was severely impaired. Serial transplantation experiments demonstrated that C/EBP beta deletion resulted in decreased outgrowth potential and premature MaSC senescence. In accord, fluorescence-activated cell sorting analysis demonstrated that C/EBP beta-null MECs contained fewer MaSCs, the loss of luminal progenitors and an increase in differentiated luminal cells as compared with wild-type. Gene profiling of C/EBP beta-null stem cells revealed an alteration in cell fate specification, exemplified by the expression of basal markers in the luminal compartment. Thus, C/EBP beta is a critical regulator of both MaSC repopulation activity and luminal cell lineage commitment. These findings have critical implications for understanding both stem cell biology and the etiology of different breast cancer subtypes.

Reporter transgene, knockout, and misexpression studies support the notion that Wnt/beta-catenin signaling regulates aspects of branching morphogenesis, regional specialization of the epithelium and mesenchyme, and establishment of progenitor cell pools. As demonstrated for other foregut endoderm-derived organs, beta-catenin and the Wnt/beta-catenin signaling pathway contribute to control of cellular proliferation, differentiation and migration. However, the contribution of Wnt/beta-catenin signaling to these processes is shaped by other signals impinging on target tissues. In this review, we will concentrate on roles for Wnt/beta-catenin in respiratory system development, including segregation of the conducting airway and alveolar compartments, specialization of the mesenchyme, and establishment of tracheal asymmetries and tracheal glands.