Journal des biomarqueurs moléculaires et du diagnostic

Paranoid schizophrenia is one of several types of schizophrenia, a chronic mental illness in which a person loses touch with reality. The classic features of paranoid schizophrenia are having delusions and hearing things that aren’t real. Based on Numerous studies about dopamine and schizophrenia, it suggested that changes in the dopamine systems are in related with schizophrenia, but still there is no clear direct evidence for dopamine hypothesis in schizophrenia.

In terminated examination, 20 paranoid schizophrenia patients mRNA from white blood cells extracted, then cDNA were synthesized. After Quantitive Real-time PCR examination with the related primaries for D1-D4 receptors were terminated and the compared consequences in abundance of genes expression with the normal samples reveal that D1-D4 dopamine receptors were expressed in all samples. Abundance of normal individuals were D1 100%, D2 6.6%, D3 40%, D4 86.6% and for patients were D1 100%, D2 26.6%, D3 33.3%, D4 73.3%. The results of this study reveals significant differences between D3 receptor apply to others. Therefore D3 has a possible clinical significance for using as rapid diagnosis of people who suspicious of paranoid schizophrenia.

Background: A crucial step in tumorigenesis is the recruitment of novel vasculature to the site of neoplasia. Currently, a number of high throughput techniques are employed to identify genes, mRNA and proteins that are aberrantly expressed in tumor vasculature. One drawback of such techniques is the lack of functional in vivo data that they provide. Bacteriophage (phage) display has been demonstrated in vivo to select peptides that home to tumors and tumor vasculature. The peptides can be compared to sequences of putative cancer-related proteins, in order to identify novel proteins essential for tumorigenesis.

Objectives: It was hypothesized that an in vivo selection for phage which targeted human breast cancer xenografts could identify peptides with homology to cancer-related proteins for in vivo imaging of breast cancer.

Methods: Following four rounds of in vivo selection in human MDA-MB-435 breast cancer xenografted mice, peptide 3-G03 was discovered with significant homology to a putative secreted protein termed EGFL6. Egfl6 mRNA is upregulated in several transcriptomic analyses of human cancer biopsies, and the protein may play a role in tumor vascularization.

Results: Egfl6 mRNA expression was demonstrated in MDA-MB-435 cells and EGFL6 protein was secreted from these cells. Based on homology of 3-G03 to EGFL6, an EGFL6 peptide was synthesized and shown to target MDA-MB-435 cells. EGFL6 peptide was radiolabeled with 111In and analyzed for biodistribution and tumor imaging capabilities. Single photon emission computed tomography imaging revealed uptake of the peptide in a manner consistent with other tumor vasculature targeting agents.

Clinical studies show that malnutrition and protein metabolic impairment in industrialised countries, is present in about 45% of elderly hospitalised patients, particularly with chronic diseases. Impairment of protein metabolism causes significant loss of body proteins including muscular proteins with sarcopenia, cachexia, morbidity and increased hospital stay and mortality. In anticipation of more sophisticated genetic and/or molecular biomarkers, here we have presented a simple rationale for the use of repeatable biomarkers that could be performed routinely at the bed-side of chronic patients. This could help clinicians to early identify and monitor protein metabolism impairment. Identifying and treating protein metabolism related abnormalities before they become irreversible and dangerous, is indispensable for the success of any therapeutic schedule.

One of the most common causes of mortality in the world is cancer. In spite of advancement in cancer treatments, the clinical outcome is far away from expectation yet. Drug resistance remains a major obstacle to the effective cure of almost all of the cancers. Telomerase is a ribonucleoprotein enzyme that contains an extremely conserved reverse transcriptase (TERT) component and a template RNA component (TERC or TR). Telomerase activity is infrequently present in normal somatic cells, but it is observed in most cancer cells. This enzyme is actually a key enzyme for human cells to acquire immortality. This study was conducted to investigate possible association between telomerase expression and clinicopathological features as well as the feasible correlation between telomerase expression and clinical response to chemotherapy in Iranian colorectal cancer patients. In this regards tumoral and adjacent normal tissues of 50 colon cancer patients were assessed for the expression level of telomerase quantitative PCR. A significant correlation was found between telomerase expression level and the stage of cancer. hTERT expression level was significantly increased in early stage tumors. No association was seen between telomerase expression and other clinical features such as age, size of the tumor, lymph node involvement. Regarding to the observations, it seems expression changes of hTERT can be employed as an important marker in the diagnosis of human colorectal cancer at an early stage after performing some complementary tests.

Background: Numerous mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene determine the response of many patients with Non-Small Cell Lung Carcinoma (NSCLC) to anti-EGFR Tyrosine Kinase Inhibitors (TKIs). This paper describes a single closed-tube assay for simultaneous mutational scanning of EGFR exons 18-21 using Linear-After-The-Exponential (LATE)-PCR and Lights-On/Lights-Off probes.

Methods: The assay first co-amplifies all four exons as separate single-stranded DNA products using LATEPCR. The amplicons are then interrogated at endpoint along their length using sets of Lights-On/Lights-Off probes of a different color for each exon. The four resulting fluorescent signatures are unique for each underlying DNA sequence. Every mutation in a target potentially alters its unique fluorescent signature thereby revealing the presence of the mutation.

Results: The assay readily detects mutations which cause sensitivity or resistance to TKIs and can distinguish these clinically important geneticchanges from silent mutations which have no impact on protein function. The assay identifies as little as 5% mutant sequences in mixtures of normal DNA and mutant DNA prepared from cancer cell lines. Proof-of-principle experiments demonstrate mutation identification in formalin-fixed, paraffin-embedded NSCLC biopsies.

Conclusion: The LATE-PCR EGFR assay described here represents a new type of highly informative, singletube diagnostic test for mutational scanning of multiple gene coding regions and/or multiple gene targets for personalized cancer therapies.

Background: Serum biomarkers of metabolic syndrome predict abnormal lung function in World Trade Center particulate matter (WTC-PM)-exposed Fire Department of New York (FDNY) rescue workers. In animal models, exposure to ambient PM induces non-alcoholic fatty liver disease (NAFLD), a well-known comorbidity of metabolic syndrome. YKL-40 is an inflammatory biomarker for both liver and lung disease. We tested if YKL-40 is a biomarker for NAFLD in this dust-exposed cohort.

Methods: Using a nested case-control design, we studied 131 FDNY personnel who had Computer Tomography performed within 5 years post 9/11. NAFLD was defined by a liver/spleen attenuation ratio of ≤1. Serum biomarkers, lipid panel and liver function were measured in serum that had been drawn within 6 months of September 11, 2001. YKL-40 and chitotriosidase were assayed by ELISA. We tested biomarker and NAFLD association using logistic regression adjusted for age, BMI, and post-911 lung function.

Results: NAFLD was present in 29/131 (22%) of the cohort. In a multivariable model increasing YKL-40 was protective while increasing triglyceride and alkaline phosphatase were risk factors for NAFLD. Conclusions: Increased YKL-40 is a protective biomarker in non-alcoholic fatty liver disease. Further studies may reveal a link between PM-induced lung and liver diseases.

Objective: Breast cancer is the most commonly occurring female cancer in the world the incidence of which is more than double that of the second ranked cancer (cervical cancer). Not many studies have assessed the relationship between biomarkers of inflammation and long-term survival in breast cancer patients. The aim of this study was to determine whether circulating markers of inflammation (CRP and TNF-α), measured before and after chemotherapy, predict response to therapy.

Material: A total of 30 histological confirmed cases of breast cancer were enrolled for study. Total duration of study was two years. HsCRP was determined by solid phase direct sandwich ELISA method (Diaclore, France). Similarly TNF-α was also determined by Enzyme-linked immunosorbent method. Three-dimensional tumor size was determined radiologically through mammography. CT scan and MRI scan were taken at the time of diagnosis to detect metastasis.

Result: The mean values of hsCRP and TNF-α in patients of breast tumor decreased after three cycles of chemotherapy and this decrease was highly significant in patients with partial/complete response to chemotherapy. Similarly, levels of hsCRP and TNF-α were high in patients with estrogen receptor positive status than in estrogen receptor negative status. No significant correlation was observed between levels of hsCRP and TNF-α with progesterone receptor status and Her 2 neu status.

Conclusion: This study shows serum hsCRP and TNF-α levels were significantly elevated in confirmed cases of breast cancer and levels decreased after chemotherapy in patients showing response to it. So hsCRP and TNF-α can be used as a surrogate.

The sequencing of fungal genomes is advancing at breakneck-speed, producing voluminous amounts of data. Within the next five years, it is possible that over a couple thousandgenomes, representing every major fungal family will be completed and available to the scientific community. In order for this data to have a truly transformative effect on mycological and other research, however, several factors need to be addressed. These include; (1) the establishment of user friendly platforms for examining, sorting, and sifting through the genomes, (2) integration, or at least cross-communication, between the various databases that house the genomic data, and (3) investment in community resources that can act as repositories for and provide materials to researchers, i.e. strains, clones, plasmids, etc. The frameworks for some these needs, e.g. the materials available from the Fungal Genetics Stock Center (FGSC, University of Missouri), are already established and should be reinforced, whereas for others, e.g. data accessibility, the sooner that a plan can be implemented the better. The Fungal Kingdom is considered to contribute greater than 15% of the species richness found in the major groups of organisms .This study is a reflection of the usefulness of sequence analysis of the 28S ribosomal RNA gene in identifying fungal as well as determining fungal diversity. Various techniques that are based on utilizing the 28S rRNA have been discussed. Of critical importance is the manner in which massively parallel sequencing was exploited to correct the under representation of fungal species in compilations of fungal hat were drawn using traditional methods of surveying fungal species from ecosystems.