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Molecular Biomarkers & Diagnosis

ISSN: 2155-9929

Open Access

Volume 5, Issue 5 (2014)

Research Article Pages: 1 - 5

Correlation among MDR1, MRP and hTERT Genes Expression Level and Clinical Response in Colorectal Cancer Patients

Samira Shabani, Sara Samanian, Rezvan Mirzaei, Bahar Mahjoubi and Frouzandeh Mahjoubi

DOI: 10.4172/2155-9929.1000187

Introduction: Colon cancer is one of the common cancers in the world. Despite current advances in the treatments of cancer, the clinical result is far away from expectation yet. Drug resistance is still a major obstacle in treatment of cancer .In this study, we attempted to investigate the possible correlation among MRP1, MRP and hTERT expression level and multidrug resistance in colon cancer patients.

Materials and Methods: Tumor and adjacent normal tissues from 35 colorectal cancer patients were assessed for the mRNA expression level of MDR1, MRP and hTERT by Real Time RT-PCR.

Results: A statistically significant increase in MDR1 and hTERT expression level was observed in tumoral tissues in comparison with normal tissues. However MRP expression level was not significantly increased in tumoral tissues. Furthermore, no correlation was seen among MDR1, MRP and hTERT expression level.

Conclusion: MDR1 and hTERT have no direct correlation, but mRNA expression of these two genes in addition to other factors indirectly helps to tumorgenesis and cancer progression.

Research Article Pages: 1 - 5

The Utility of Pyrogenic Cytokine (IL-1β, TNF-α and IL-6) Detection In Risk Stratification of Critically lll Febrile Patients in Emergency Department

Francesco Travaglino, Gerardo Salerno, Veronica Russo, Mariateresa Corsetti, Rosaria D’Urso, Patrizia Cardelli, Maria Rosaria Torrisi, Vincenzo Visco and Salvatore Di Somma

DOI: 10.4172/2155-9929.1000188

Objective: Aim of our study was to evaluate the prognostic value of pyrogenic cytokines (IL-1β, TNF-α and IL-6) detection associated with Mid regional pro-Amedullin (MR-proADM) and the APACHE II score in febrile patients admitted to the Emergency Department (ED).

Material: 64 patients in the Emergency Room (ER) during a period of 12 months with body temperature >37°C were recruited for this study. In order to compare MR-proADM and cytokine values, a control group of 40 healthy volunteers was enrolled. For each subject, the APACHE II score was calculated.

Result: MR-proADM and cytokines were significantly higher in patients compared to controls (p<0.0001). When APACHE II score was correlated to MR-proADM and cytokines and grouped into quartile, it showed a significant increase in TNF-α and IL-6 levels (p<0.0001). A significant stepwise increase in MR-proADM in accordance with IL-6 quartile levels was observed (p<0.0001). The receiver operating characteristic (ROC) curve showed the ability of those combined biomarkers to predict hospitalization.

Conclusion: The combined use of MR-proADM and cytokines can help the febrile patient’s management in the ED, predicting a subsequent hospitalization of such individuals.

Research Article Pages: 1 - 6

Osteochondrosis-Related Gene Expression in Equine Leukocytes Differs among Affected Joints in Foals

Serteyn D, Piquemal D, Mendoza L, Caudron I, Noguier F, Bruno R, Sandersen C and Lejeune JP

DOI: 10.4172/2155-9929.1000189

Osteochondrosis (OC) is a developmental disease in horses with a significant impact on the horse’s welfare and performance. Previously, differentially expressed genes in leukocytes of OC-affected have been identified and were differentially expressed in horses of different ages when compared to their age-matched controls.As the time course of the development of OC lesions seems to be joint dependent,the aim of this study is to compare in young OCaffected horses (between 8 to 12 months), the different expression of selected genes depending the joints involved.The expression of OC-related genes were analysed by rt-PCR and subsequent statistical analysis (ΔΔCT) in the leukocytes of 30 Belgian Warmblood horses aged between 8 to 12 months divided in groups depending the affected joints (fetlock, hock and stifle).In the three groups, expression of ApoB-3G, MGAT4A, B4GALT6 and PRKCG genes were significantly higher in the OC-affected foals compared to the healthy foals. Based on the profiles of expression ofApoB-3G, Dsh1/Dvl1, Foxl1, Hp, ISG15, Mark2, PPR2A, RUSC2 and WASH1 genes,the localization of the disease can be determined: expression levels of ApoB3G, WASH1 and FOXl1 to identify fetlock, ApoB3G, PPR2A to identify OC-development in the hock and ApoB3G, Dsh1/Dvl1, WASH1, PPP2R1A and Mark2 geneto identify OC-development in the stifle. However at this moment, the rt-PCR analysis of the identified genes as biomarkers gives only diagnostic information. For the future, the profile of expression of these genes could give also some predictive information on the evolution of the disease such as remission or permanent OC-lesions.

Research Article Pages: 1 - 9

Evaluation and Identification of Protein Blood Biomarkers for Alzheimer's Disease: A Systematic Review and Integrative Analysis

Junseong Park, JiEun Park, Jungsul Lee and Chulhee Choi

DOI: 10.4172/2155-9929.1000190

Background: Alzheimer’s disease (AD) accounts for 80% of all dementia, but current treatment cannot provide definite cure. For this reason, researchers seek highly accurate preclinical biomarkers for minimal cognitive impairment. This study aimed to evaluate sporadically reported protein blood biomarkers (BBs) of AD and suggest new protein BB candidates for AD. Methods: A systematic PubMed review was performed on articles published between 1989 and March 2013, and several articles and protein BBs of AD were screened based on eligibility criteria and quality. An integrative analysis was conducted to evaluate reported protein BBs and identify new protein BB candidates. Results: In total, 67 articles were included; 95 protein BBs were evaluated through a meta-scoring system based on five criteria. The highest meta-scored protein BB was Serpin A3 (meta-score: 36) followed by tumor necrosis factor-α(meta-score: 35). An integrative analysis using a protein-protein interaction (PPI) network revealed that 67 proteins are linked via 97 edges. In an extended PPI network, 105 proteins were connected via 240 edges and 63 linker molecules were discovered as new protein BB candidates. Conclusion: This study showed a total of 95 meta-scored protein BBs and identified 63 new biomarker candidates of AD.

Research Article Pages: 1 - 5

Interleukin 23 P 19 Expression in Patients with Ulcerative Colitis and Its Relation to Disease Severity

Hanan El-Bassat, Lobna Abo Ali, Sahar El Yamany, Hanan Al Shenawy, Rasha A Al Din and Atef Taha

DOI: 10.4172/2155-9929.1000191

Background and study aims: The purpose of this study is to determine whether mucosal expression of IL 23 p 19 has role in the pathogenesis of ulcerative colitis and its relation to disease severity.

Materials and methods: This study was carried out on 50 patients with ulcerative colitis and 10 normal individuals as control. They were divided into: Group I: 27 patients with mild to moderate disease. Group II: 23 patients with severe disease. Group III: 10 normal individuals. All patients and control were subjected to histopathological study, IL-23p19 immunohistochemical staining, IL-23R expression by flow cytometry and serum IL-23 by ELISA.

Results: There is significant increased in IL-23p19 gene and IL-23R in ulcerative colitis patients compared with control. Significant positive correlation was detected between increased expression of IL-23 p19 gene, IL-23R, high serum IL-23 and severity of the disease.

Conclusions: increased expression of IL-23 p19 is associated with ulcerative colitis and may indicate a role in its pathogenesis and that targeted therapy directed against IL-23 p19 may be effective in the treatment. Also increased expression of IL-23p19 gene and IL-23R with high serum IL-23 correlate positively with disease severity.

Research Article Pages: 1 - 6

Significance of Macrophage Migration Inhibitory Factor (MIF) and Anti P 53 Antibodies in Prognosis of Hepatocellular Carcinoma

Lamiss Mohamed Abd Elaziz Sad, Samar Galal Younis and Hala Mohamed Nagi

DOI: 10.4172/2155-9929.1000192

Background and aim: Prognosis of hepatocellular carcinoma (HCC) is very poor and determining the prognosis rely many factors and we aim at defining the prognostic factor of macrophage migration inhibitory factor (MIF) , anti P53 and its correlation with other prognostic factors in HCC.

Patients: Serum macrophage migration inhibitory factor and anti-p53 antibodies were measured in139 patients diagnosed with HCC using a specific enzyme-linked immunosorbent assay (ELISA) kit. The clinicopathological characteristics of the patients were compared with respect to the presence of serum anti-p53 antibodies.

Results: In univariate analysis, the prognostic factors of overall survival with statistical significance were portal vein thrombosis, total serum bilirubin, serum albumin, serum AST, serum ALT, Prothrombin time, viral marker and anti p53 antibody and MIF and on multivariate analysis the prognostic factors were BCLC staging, presence of extrahepatic metastases, the patient received treatment or not, anti p53 antibody and MIF.

Conclusion: Both MIF and Anti p53 antibody are associated with poor prognosis in HCC and it increased the prognostic potential of alpha fetoprotein.

Research Article Pages: 1 - 5

Prognostic Value of Bone Marker Beta-Crosslaps in Patients with Breast Carcinoma

Nicole Zulauf, Ingo Marzi and Gerhard M Oremek

DOI: 10.4172/2155-9929.1000193

Background: This study investigated the usefulness of bone markers Alkaline Phosphatase (AP) and Beta- Crosslaps (ß-CTx) to diagnose, treat and monitor patients with breast carcinoma. AP is a marker of bone formation, while ß-CTx are markers of bone resorption. ß-CTx are expressed as degradation products of collagen type I and can be measured in blood and urine.

Objectives: The aim of this project was to evaluate the significance of bone markers ß-CTx and AP with regard to their usage for early diagnostics of bone metastases and pathological bone metabolism in pre- and postmenopausal patients with known breast cancer.

Materials and Methods: Peripheral blood samples of patients with mammarial diseases (benign and malign) were collected and the bone markers AP and ß-CTx determined. A total number of 110 patients had benign mammarial diseases, BMD (30 fibroadenoma, 50 mastopathy and 30 hypertrophy patients). 30 patients were suffering from a malignant breast cancer without bone metastases. 50 patients had known bone metastases. The determination of ß-CTx was conducted based on the Immunoassay “ECLIA”, the analysis approach Elecsys 2010 and cobase by Roche Diagnostics (Mannheim, Germany). The analysis of AP was performed with the HYDRAGEL ISO-PAL kits and HYDRASYS electrophoresis system of Sebia (Fulda, Germany).

Results: For the detection of bone metastases, the study showed a sensitivity of 94.0% with 86.67% specificity for AP. Results for ß-CTx had a sensitivity and specificity of 100.0%. An elevated ß-CTx activity was associated significantly with bone metastases in the study groups (p=0.000000). Furthermore there were significant differences (p=0.000000) due to the menopausal status of patients.

Conclusion: In conclusion ß-CTx are more sensitive and specific to detect bone metastases and bone turnover than AP. In patients with multimorbidity the origin of AP is not clear due to its multi-organic appearance. Hence ß- CTx are considered to be helpful in the diagnostic procedure of breast cancer-patients to detect bone metastases. Moreover they can be utilized to indicate patients with early dysfunctions in bone metabolism and allow inducing early treatment. ß-CTx as indicators of bone resorption are capable to provide a significant differentiation between mamma-carcinoma patients with and without bone affection.

Research Article Pages: 1 - 4

Targeted Next-generation Sequencing Reveals a Homozygous Nonsense Mutation in CAPN3 that Causes Limb-girdle Muscular Dystrophy Type 2A First in Vietnam

Emma Tabe Eko Niba, Van Khanh Tran, Le Anh Tuan-Pham, Dung Chi Vu, Ngoc Khanh Nguyen, Thinh Huy Tran, Van Thanh Ta, Tomoko Lee, Yasuhiro Takeshima and Masafumi Matsuo

DOI: 10.4172/2155-9929.1000194

Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous entity characterized by progressive wasting of the shoulder and pelvic-girdle muscles. Diagnosing particular types of LGMD is still challenging, especially in developing countries, with targeted next-generation sequencing (NGS) emerging as the most advanced diagnostic tool. Here, a 15-year-old Vietnamese girl with proximal muscle weakness was examined for genetic cause via targeted NGS using the AmpliSeq Inherited Disease Ready-to-Use Panel on the Ion Torrent Personal Genome Machine of the detected nucleotide changes, a mutation in exon 3 of CAPN3 was considered to be the responsible mutation. In the readpile-ups, only T was observed at the 424th nucleotide, while only C was observed in the normal sample. The c.424 C>Ttransition in CAPN3 shifted glutamine to a stop codon at the 142nd amino acid residue (p.Q142X). The homozygous c.424C>T genotype was confirmed via XspI restriction enzyme digestion using polymerase chain reaction-amplified product from the index case encompassing exon 3.The patient was concluded to be autosomal recessive LGMD type 2A. XsaIdigestion of 100 control Vietnamese genomes disclosed one carrier of this mutation. Thus, LGMD type 2Awas first diagnosed in Vietnam, a developing country, via targeted NGS, avoiding invasive muscle biopsy.

Research Article Pages: 1 - 8

Aberrant Hypomethylated KRAS and RASGRF2 as a Candidate Biomarker of Low Level Benzene Hematotoxicity

Jing Yang, Wenlin Bai, Zhongxin Xiao, Yujiao Chen, Li Chen, Lefeng Zhang, Junxiang Ma, Lin Tian and Ai Gao

DOI: 10.4172/2155-9929.1000195

Benzene is an important industrial chemical and an environmental contaminant. The mechanisms of low level benzene-induced hematotoxicity are unresolved. Aberrant DNA methylation, which may lead to genomic instability and the altered gene expression, is frequently observed in hematological cancers. The purpose of the present study was to conduct a genome-wide investigation to examine comprehensively whether low level benzene induces DNA methylation alteration in the benzene-exposed workers. Infinium 450K methylation array was used to compare methylation levels of the low level benzene-exposed individuals and health controls and the differentially expressed DNA methylation pattern critical for benzene hematotoxicity were screened. Signal net analysis showed that two key hypomethylated KRAS and RASGRF2 associated with low level benzene exposure were identified. Further, the hypomethylated RASGRF2 gene played central roles through regulation of Rho protein, MAPK, small GTPase mediated signal transduction. While the hypomethylated KRAS gene played important roles through small GTPase, Ras protein, MAPK cascade, Gap junction, Axon guidance, Tight junction, GnRH, T cell receptor signaling pathway, Acute myeloid leukemia, B cell receptor signaling pathway, Chronic myeloid leukemia, ErbB signaling pathway. Our preliminary study indicated that aberrant hypomethylated KRAS and RASGRF2 might be a potential methylated biomarker of low level benzene hematotoxicity.

Review Article Pages: 1 - 7

The Free Alpha-Hemoglobin: A Promising Biomarker for β-Thalassemia

Uday YH Abdullah, Ahmed GF Al-Attraqchi, Hishamshah M Ibrahim, Zilfalil Bin Alwi, Atif A Baig, Iekhsan Othman, Noraesah B Mahmud, Rosline B Hassan, Nor Hedayah A Bakar and Alawiyah B A Abd Rahman

DOI: 10.4172/2155-9929.1000197

The purpose is to review the current knowledge and methods of determination of the free alpha hemoglobin with emphasis on its potential implications in patients with beta-thalassemia (β-thal).The severity of β-thal correlates with the extent of imbalance between α- and non-α-globin chains and the amount of the free alpha hemoglobin (free α- Hb) pool in the erythrocytes. To date, there is a lack of biomarkers that convey diagnostic and prognostic values in β-thal. Our ongoing research is aimed to evaluate the potential prognostic and diagnostic implications of free α-Hb to improve the care of patients with β-thal. Our ongoing research is aimed to quantify the free α-Hb for its potential prognostic and diagnosticimplications towards improving the care of patients with various β-thal types in the years to come.

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Citations: 2054

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