BioMed Central - Latest Articles

Relationship between tumor size and disease stage in non-small cell lung cancer

Fu Yang — 2010-09-02T00:00:00Z

Background: Whether tumor size and stage distribution are correlated remains controversial. The objective is to assess the relationship between tumor size and disease stage distribution in non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 917 cases of NSCLC that were resected in the Cancer Hospital of Fudan University and Shanghai Sixth Hospital between January 2000 and February 2009. Tumor sizes were grouped into five categories: [less than or equal to]20 mm, 21 to 30 mm, 31 to 50 mm, 51 to 70 mm and [greater than or equal to]71 mm. Results: Age and tumor size affected stage distribution: patients 60 years or older had a higher percentage of N0M0 disease than patients younger than 60 years (61.67% vs. 44.85%, p<0.01). The smaller the tumor, the more likely the disease was N0M0 status (p<0.05). For tumors [less than or equal to]20 mm in diameter, the proportion of cases with N0M0 status was 70.79%, compared to 58.88% for 21 to 30 mm, 48.03% for 31 to 50 mm, 47.55% for 51 to 70 mm, 33.33% for [greater than or equal to]71 mm. The mean (+/-SD) tumor size of cases with N0M0 status was 37.17+/-21.34 mm, compared to 45.75+/-23.19 mm for cases with other status. Conclusions: There is a statistically significant relationship between tumor size and distribution of disease stage of primary NSCLC tumors: the smaller the tumor, the more likely the disease is N0M0 status.

Echocardiographic imaging of tricuspid and pulmonary valve abnormalities in primary ovarian carcinoid tumor

Constantina Aggeli — 2010-09-02T00:00:00Z

Carcinoid is a rare malignancy originating from enterochromaffin cells and is clinically characterized by flushing, diarrhea and bronchospasm, due to secretion of vasoactive substances. A dreaded complication is carcinoid heart disease, which mainly affects right cardiac chambers, resulting in thickened, immobile and retracted tricuspid and pulmonary valves. In the current report, a case of a 60-year old female presenting with symptoms of right heart failure is described. Transthoracic two-dimensional and real-time three-dimensional echocardiography findings, as well as biochemical markers, including pro-BNP and NT-pro-BNP, were consistent with carcinoid syndrome. The histological diagnosis of carcinoid was confirmed after surgical resection of an ovarian mass.

Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis

Celine Sabatel — 2010-09-02T00:00:00Z

Background: Disorganized angiogenesis is associated with several pathologies, including cancer. The identification of new genes that control tumor neovascularization can provide novel insights for future anti-cancer therapies. Sprouty1 (SPRY1), an inhibitor of the MAPK pathway, might be one of these new genes. We identified SPRY1 by comparing the transcriptomes of untreated endothelial cells with those of endothelial cells treated by the angiostatic agent 16K prolactin (16K hPRL). In the present study, we aimed to explore the potential function of SPRY1 in angiogenesis. Results: We confirmed 16K hPRL induced up-regulation of SPRY1 in primary endothelial cells. In addition, we demonstrated the positive SPRY1 regulation in a chimeric mouse model of human colon carcinoma in which 16K hPRL treatment was shown to delay tumor growth. Expression profiling by qRT-PCR with species-specific primers revealed that induction of SPRY1 expression by 16K hPRL occurs only in the (murine) endothelial compartment and not in the (human) tumor compartment. The regulation of SPRY1 expression was NF-kappaB dependent. Partial SPRY1 knockdown by RNA interference protected endothelial cells from apoptosis as well as increased endothelial cell proliferation, migration, capillary network formation, and adhesion to extracellular matrix proteins. SPRY1 knockdown was also shown to affect the expression of cyclinD1 and p21 both involved in cell-cycle regulation. These findings are discussed in relation to the role of SPRY1 as an inhibitor of ERK/MAPK signaling and to a possible explanation of its effect on cell proliferation. Conclusions: Taken together, these results suggest that SPRY1 is an endogenous angiogenesis inhibitor.

Correction: Reduction of late stillbirth with the introduction of fetal movement information and guidelines - a clinical quality improvement

Julie Victoria Holm Tveit — 2010-09-02T00:00:00Z

We have performed a full cross-validation of this clinical Femina data collection against the routinely collected data of the Medical Birth Registry of Norway to validate the estimates ofreduced mortality in the total population. The original estimate of fewer deaths during the intervention with OR 0.7 remains virtually unchanged for the original data collection.The validation procedures revealed inaccuracies in data from the Medical Birth Registry of Norway for a partial comparison with mortality outside the study area, and we here correctthis comparison. We present new, corrected and cross-validated data. Despite comparability issues, the most robust and cross-validated estimates confirm similar estimates of reducedmortality during the quality improvement intervention.

Automatic detection of anchor points for multiple sequence alignment

Florian Pitschi — 2010-09-02T00:00:00Z

Background: Determining beforehand specific positions to align (anchor points) has proved valuable for the accuracy of automated multiple sequence alignment (MSA) software. This feature can be used manually to include biological expertise, or automatically, usually by pairwise similarity searches. Multiple local similarities are be expected to be more adequate, as more biologically relevant. However, even good multiple local similarities can prove incompatible with the ordering of an alignment. Results: We use a recently developed algorithm to detect multiple local similarities, which returns subsets of positions in the sequences sharing similar contexts of appearence. In this paper, we describe first how to get, with the help of this method, subsets of positions that could form partial columns in an alignment. We introduce next a graph-theoretic algorithm to detect (and remove) positions in the partial columns that are inconsistent with a multiple alignment. Partial columns can be used, for the time being, as guide only by a few MSA programs: ClustalW 2.0, DIALIGN 2 and T-Coffee. We perform tests on the effect of introducing these columns on the popular benchmark BAliBASE 3. Conclusions: We show that the inclusion of our partial alignment columns, as anchor points, improve on the whole the accuracy of the aligner ClustalW on the benchmark BAliBASE 3.

Identification of tumor-associated cassette exons in human cancer through EST-based computational prediction and experimental validation

Alessio Valletti — 2010-09-02T00:00:00Z

Background: Many evidences reports that alternative splicing, the mechanism which produces mRNAs and proteins with different structures and functions from the same gene, is altered in cancer cells. Thus, the identification and characterization of cancer-specific splice variants may give large impulse to the discovery of novel diagnostic and prognostic tumour biomarkers, as well as of new targets for more selective and effective therapies. Results: We present here a genome-wide analysis of the alternative splicing pattern of human genes through a computational analysis of normal and cancer-specific ESTs from seventeen anatomical groups, using data available in AspicDB, a database resource for the analysis of alternative splicing in human. By using a statistical methodology, normal and cancer-specific genes, splice sites and cassette exons were predicted in silico. The condition association of some of the novel normal/tumoral cassette exons was experimentally verified by RT-qPCR assays in the same anatomical system where they were predicted. Remarkably, the presence in vivo of the predicted alternative transcripts, specific for the nervous system, was confirmed in patients affected by glioblastoma. Conclusion: This study presents a novel computational methodology for the identification of tumor-associated transcript variants to be used as cancer molecular biomarkers, provides its experimental validation, and reports specific biomarkers for glioblastoma.

p21Waf1 expression is regulated by nuclear intermediate filament vimentin in neuroblastoma

Xenia Mergui — 2010-09-02T00:00:00Z

Background: Human neuroblastoma (NB) cell lines may present with either one of the so-called S-and N-subtypes. We have previously reported a strong correlation between protein expression levels of vimentin, an S-subtype marker, and the p21Waf1 cyclin-dependent kinase inhibitor. We here investigated whether this correlation extend to the mRNA level in NB cell lines as well as in patients' tumors. We also further explored the relationship between expression of vimentin and p21, by asking whether vimentin could regulate p21 expression. Methods: Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (n=77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB patients (n=40) were analyzed in relation with the overall survival using the Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of vimentin in highly or low expressing vimentin cell lines, respectively, followed by protein expression and promoter activation assays were used to assess the role of vimentin in modulating p21 expression. Results: We extend the significant correlation between vimentin and p21 expression to the mRNA level in NB cell lines as well as in patients' tumors. Overall survival analysis from Q-PCR data obtained from tumors of high risk patients suggest that lower levels of p21 expression could be associated with a poorer outcome. Our data additionally indicate that the correlation observed between p21 and vimentin expression levels results from p21 transcriptional activity being regulated by vimentin. Indeed, downregulating vimentin resulted in a significant decrease in p21 mRNA and protein expression as well as in p21 promoter activity. Conversely, overexpressing vimentin triggered an increase in p21 promoter activity in cells with a nuclear expression of vimentin. Conclusion: Our results suggest that p21 mRNA tumor expression level could represent a refined prognostic factor for high risk NB patients. Our data also show that vimentin regulates p21 transcription; this is the first demonstration of a gene regulating function for this type III-intermediate filament.

Gene expression following induction of regeneration in Drosophila wing imaginal discs

Enrique Blanco — 2010-09-02T00:00:00Z

Background: Regeneration is the ability of an organism to rebuild a body part that has been damaged or amputated, and can be studied at the molecular level using model organisms. Drosophila imaginal discs, which are the larval primordia of adult cuticular structures, are capable of undergoing regenerative growth after transplantation and in vivo culture into the adult abdomen. Results: Using expression profile analyses, we studied the regenerative behaviour of wing discs at 0, 24 and 72 hours after fragmentation and implantation into adult females. Based on expression level, we generated a catalogue of genes with putative role in wing disc regeneration, identifying four classes: 1) genes with differential expression within the first 24 hours; 2) genes with differential expression between 24 and 72 hours; 3) genes that changed significantly in expression levels between the two time periods; 4) genes with a sustained increase or decrease in their expression levels throughout regeneration. Among these genes, we identified members of the JNK and Notch signalling pathways and chromatin regulators. Through computational analysis, we recognized putative binding sites for transcription factors downstream of these pathways that are conserved in multiple Drosophilids, indicating a potential relationship between members of the different gene classes. Experimental data from genetic mutants provide evidence of a requirement of selected genes in wing disc regeneration. Conclusions: We have been able to distinguish various classes of genes involved in early and late steps of the regeneration process. Our data suggests the integration of signalling pathways in the promoters of regulated genes.

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

Chun-Zhi Zhang — 2010-09-02T00:00:00Z

Background: MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive. Results: Here we showed that miR-221/222 inhibited cell apoptosis by targeting proapoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3' UTR. Introducing PUMA cDNA without 3' UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues. Conclusion: To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.

Genome3D: a viewer-model framework for integrating and visualizing multi-scale epigenomic information within a three-dimensional genome

Thomas Asbury — 2010-09-02T00:00:00Z

Background: New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation. Results: We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order to integrate and visualize large volume of data, novel statistical and mathematical approaches have been developed to reduce the size of the data. To our knowledge, this is the first such tool developed that can visualize human genome in three-dimension. We describe here the major features of Genome3D and discuss our multi-scale data framework using a representative basic physical model. We then demonstrate many of the issues and benefits of multi-resolution data integration. Conclusions: Genome3D is a software visualization tool that explores a wide range of structural genomic and epigenetic data. Data from various sources of differing scales can be integrated within a hierarchical framework that is easily adapted to new developments concerning the structure of the physical genome. In addition, our tool has a simple annotation mechanism to incorporate non-structural information. Genome3D is unique in its ability to manipulate large amounts of multi-resolution data from diverse sources to uncover complex and new structural relationships within the genome.