ELF3 is an antagonist of oncogenic-signalling-induced expression of EMT-TF ZEB1.

Background: Epithelial-to-mesenchymal transition (EMT) is a key step in the transformation of epithelial cells into migratory and invasive tumour cells. Intricate positive and negative regulatory processes regulate EMT. Many oncogenic signalling pathways can induce EMT, but the specific mechanisms of how this occurs, and how this process is controlled are not fully understood. Methods: RNA-Seq analysis, computational analysis of protein networks and large-scale cancer genomics datasets were used to identify ELF3 as a negative regulator of the expression of EMT markers. Western blotting coupled to siRNA as well as analysis of tumour/normal colorectal cancer panels was used to investigate the expression and function of ELF3. Results: RNA-Seq analysis of colorectal cancer cells expressing mutant and wild-type ß-catenin and analysis of colorectal cancer cells expressing inducible mutant RAS showed that ELF3 expression is reduced in response to oncogenic signalling and antagonizes Wnt and RAS oncogenic signalling pathways. Analysis of gene-expression patterns across The Cancer Genome Atlas (TCGA) and protein localization in colorectal cancer tumour panels showed that ELF3 expression is anti-correlated with ß-catenin and markers of EMT and correlates with better clinical prognosis. Conclusions: ELF3 is a negative regulator of the EMT transcription factor (EMT-TF) ZEB1 through its function as an antagonist of oncogenic signalling.

Genetic analysis of Iranian autosomal dominant polycystic kidney disease: new insight to haplotype analysis.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) caused by mutations in two PKD1 and PKD2 genes. Due to the complexity of the PKD1 gene, its direct mutation screening is an expensive and time-consuming procedure. Pedigree-based haplotype analysis is a useful indirect approach to identify the responsible gene in families with multiple affected individuals, before direct mutation analysis. Here, we applied this approach to investigate 15 appropriate unrelated ADPKD families, selected from 25 families, who referred for genetic counseling. Four polymorphic microsatellite markers were selected around each PKD1 and PKD2 loci. In addition, by investigating the genomic regions, two novel flanking tetranucleotide STR markers were identified. Haplotype analysis and calculating Lod score confirmed linkage to PKD1 in 9 families (60%) and to PKD2 in 2 families (13%). Linkage to both loci was excluded in one family (6.6%). In 2 families (13%) the Lod scores were inconclusive. Causative mutation was identified successfully by direct analysis in two families with confirmed linkage, one to PKD1 and another to PKD2 locus. The study showed that determining the causative locus prior to direct mutation analysis is an efficient strategy to reduce the resources required for genetic analysis of ADPKD families. This is more prominent in PKD2-linked families. Selection of suitable markers, and appropriate PCR multiplexing strategy, using fluorescent labeled primers and 3 primer system, will also add value to this approach.

Meridian studies in China: a systematic review.

Meridian theory is a major part of Chinese medicine and has guided acupuncture and clinical practice for thousands of years. Meridian theory describes many important concepts about the rules of human body function and regulation, but has comparatively huge differences with the basic concepts of modern medicine. These differences have caused deep concern and attracted attention from scholars, both inside and outside of China. The interest in meridian theory lies in determining the structural nature of meridians. Not only is this information still unclear, it is very difficult to achieve clear results in a short period of time. Despite this, the phenomena of meridians can be used as the entry point for meridian studies. After many years of effort, although the physical structure of meridians has not been found, the existence of the meridian phenomena has been fully confirmed. Although there is a lack of morphological evidence for the existence of the meridian, concluding non-existence may be incorrect as morphology techniques develop and structures previously not determined are being found. Since the phenomenon of meridians exists, some biological basis behind its occurrence must be present. This implies that research on meridians needs to continue as research techniques advance and may eventually reveal the biological basis of the meridian phenomenon. In the present review, we analyze the history of meridian studies in China.

Characterization of the primo-vascular system in the abdominal cavity of lung cancer mouse model and its differences from the lymphatic system.

Cancer growth and dissemination have been extensively studied for a long time. Nevertheless, many new observations on anatomy and histopathology of cancer events are still reported such as formation of a vasculogenic-like network inside aggressive tumors. In this research, new kinds of micro-conduits, named primo-vessels, were found inside the abdominal cavity of NCI-H460 lung cancer murine xenograft models. These vascular threads were largely distributed on the surfaces of various organs and were often connected to peritoneal tumor nodules. Histological and immunofluorescent investigations showed that the primo-vessels had characteristic features that were distinctively different from those of similar-looking lymphatic vessels. They had multiple channels surrounded with loose collageneous matrices, which is in contrast to the single-channel structure of other vascular systems. The rod-shaped nuclei aligned longitudinally along the channels were assumed to be the endothelial cells of the primo-vessels, but LYVE-1, a specific marker of lymphatics, was not expressed, which indicates a clear difference from lymphatic endothelial cells. Taken together these findings on and characterization of the novel threadlike vascular structures in cancer models may have important implications for cancer prognosis and for therapy.

Association of TGIFLX/Y mRNA expression with prostate cancer.

Prostate cancer is the most common type of solid tumor and a leading cause of cancer-related death of men living in the developed world. In recent years, the molecular mechanisms involved in prostate cancer development and/or progression have been intensely studied and several genes have been identified. TGIFLX/Y (TGIFLX and TGIFLY) are members of the homeobox superfamily of genes whose function(s) is unknown. To investigate TGIFLX/Y mRNA expression in prostate cancer, we studied two different types of clinical samples, namely 60 prostate tumors and 15 cases of benign prostate hyperplasia (BPH), by RT-PCR. Our results revealed that most prostate tumors (73.5%) express at least one of these genes, although different patterns of TGIFLX/Y mRNA expression were observed. In some tumor samples the expression of both genes was detected, while in others no expression of either gene was observed. Notably, there was a significant correlation between expression of both TGIFLX and TGIFLY and a Gleason score of >or=6 (P = 0.038). By contrast, expression of TGIFLX/Y mRNA in BPH samples could not be detected. These results suggest an association of TGIFLX/Y expression with the progression of prostate cancer.

Molecular cytogenetic analysis of urothelial carcinomas using urine samples.

Urinary cells obtained from voided urine specimens of 46 patients with urothelial carcinomas (UCs) and 10 normal individuals were analyzed with 3 different centromeric fluorescence in situ hybridization (FISH) probes. The overall sensitivity of cytology was 48.9% compared to 95.7%with the FISH technique. The minimum values were found for stage Ta and grade 1 (90.5 and 89.4) and sensitivity of FISH in other stages and grades was 100%. Chromosome 3 demonstrated the most frequent chromosomal abnormality in all samples (43%), followed by chromosome 17 (32%) and chromosome 7 (25%). There was a statistically significant association between the number of cell abnormalities in chromosome 17 and the tumour stage (p value=0.02). No relationship was found between the type of chromosomal abnormality and grade. Thus feasibility and reliability of a FISH based approach was confirmed for detection of UC in urine samples.

A new type of spondylo-metaphyseal dysplasia--Algerian type. Report of five cases.

A new, dominantly inherited, severe form of spondylometaphyseal dysplasia in five members of an Algerian family is reported. Another child, not investigated, was also probably affected. The disease is characterised by a unique clinical and radiological set of features: dwarfism, genu valgum deformity, progressive kypho-scoliosis, wrist deformity, myopia and severe metaphyseal dysplasia, with moderate spinal changes and minimal changes in the hands and feet. In view of the geographical localisation of the disorder and the anatomical distribution we propose the name Algerian type of spondylo-metaphyseal dysplasia.