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Authors: Ferchichi, Imen | Sassi Hannachi, Samia | Baccar, Amal | Marrakchi Triki, Raja | Cremet, Jean Yves | Ben Romdhane, Khaled | Prigent, Claude | Ben Ammar El Gaaied, Amel
Article Type: Research Article
Abstract: Aurora A kinase is overexpressed in many cancers but the status of this protein in the breast cancer often varies. We investigate the expression and localization of Aurora A protein in relation with tumor emergence and progression in breast cancer. Aurora A kinase status was evaluated in 107 patients using immunohistochemistry. The experimental findings showed that high expression of the Aurora A protein was correlated with elevated nuclear grade, low expression of progesterone receptor and positive …nodal status. The experimental results showed also that the localization of this kinase shifts from cytoplasm in non malignant adjacent tissue to both cytoplasmic and nuclear compartments in tumoral tissue, suggesting an oncogenic role of the nuclear accumulation. We have, furthermore, detected the overexpression of this protein in non malignant adjacent tissue. The expression of the Aurora A kinase in non malignant tissue may represent an earlier diagnosis tool for breast cancer. Show more
Keywords: Aurora A, breast cancer, immunohistochemistry
DOI: 10.3233/DMA-120947
Citation: Disease Markers, vol. 34, no. 2, pp. 63-69, 2013
Authors: Baig, Ruqia Mehmood | Mahjabeen, Ishrat | Sabir, Maimoona | Masood, Nosheen | Ali, Kashif | Malik, Faraz Arshad | Kayani, Mahmood Akhtar
Article Type: Research Article
Abstract: Cytoskeletal rearrangement occurs in variety of cellular processes and involves a wide spectrum of proteins. Gelsolin super family proteins control actin organization by severing and capping filament ends and nucleating actin assembly. Gelsolin is the founding member of this family and plays important role in pathogenesis of human neoplasia. This study aimed to investigate the germline mutations and expressional profile of Gelsolin in human breast cancer tissues. For germ line screening PCR-SSCP technique was …used while expression was analyzed through quantitative real time PCR. Different types of mutations were observed in Gelsolin coding regions on exons 4, 10, 11, 14 and 15. These mutations include 3 missense nonsynonymous substitution mutations, 2 deletions, 1 insertion and 1 synonymous substitution mutation. Gelsolin transcript level was found significantly lower in breast tumor tissues compared to control samples (p=0.03). Low level of Gelsolin was found in metastatic patients (p=0.002) and patients who died from breast cancer (P=0.03) compared to disease free patients at final follow up. This study shows that level of Gelsolin is down regulated in breast cancer tissues and is linked with metastasis development and death in patients. It is concluded that genetic changes in coding regions of Gelsolin can potentially contribute to genetic instability. These genetic variations and expressional correlation with patient survival may prove to be of significant importance. Show more
Keywords: Gelsolin, germline mutations, PCR-SSCP, expressional analysis, quantitative real time PCR, breast cancer
DOI: 10.3233/DMA-120952
Citation: Disease Markers, vol. 34, no. 2, pp. 71-80, 2013
Authors: Kanakis, Dimitrios | Lendeckel, Uwe | Theodosiou, Paraskevi | Dobrowolny, Henrik | Mawrin, Christian | Keilhoff, Gerburg | Bukowska, Alicia | Dietzmann, Knut | Bogerts, Bernhard | Bernstein, Hans-Gert
Article Type: Research Article
Abstract: ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, …ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours. Show more
Keywords: ADAM 12, gliomas, oligodendrogliomas, immunohistochemistry, RT-PCR
DOI: 10.3233/DMA-120953
Citation: Disease Markers, vol. 34, no. 2, pp. 81-91, 2013
Authors: Hrašovec, Sonja | Hauptman, Nina | Glavač, Damjan | Jelenc, Franc | Ravnik-Glavač, Metka
Article Type: Research Article
Abstract: The identification of novel genes involved in colorectal cancerogenesis is of high clinical relevance for early diagnosis, applying new therapeutic strategies and monitoring disease recurrence, in order to reduce disease incidence and mortality. Gene silencing through CpG island hypermethylation is a major epigenetic mechanism involved in cancer development. In our study, we aimed to identify and validate novel genes with a tumour specific DNA methylation profile in colorectal cancer. We performed a whole-genome methylation …scan and identified several possible candidate genes that are hypermethylated in tumour in comparison to healthy colon mucosa. Using methylation-specific high-resolution melting analysis in a set consisting of 133 colorectal cancer samples, we were able to confirm an altered CpG site in TMEM25 in 69.2% (92/133) tumours analysed. Furthermore, the expression of TMEM25 was found to be significantly lower in tumour tissue. An inverse correlation between hypermethylation of TMEM25 and TMEM25 down-regulated expression was observed. Our results suggest that epigenetic down-regulation of TMEM25 is cancer-related; we thus suggest that TMEM25 hypermethylation might play a significant role in altering expression of this gene in colorectal cancer. Show more
Keywords: Colorectal cancer, DNA methylation, array-based methylation profiling, high-resolution melting, TMEM25 hypermethylation, TMEM25 down-regulation
DOI: 10.3233/DMA-120948
Citation: Disease Markers, vol. 34, no. 2, pp. 93-104, 2013
Authors: Feng, Gang | Ye, Xiaobing | Fang, Fang | Pu, Chun | Huang, Houbao | Li, Guorong
Article Type: Research Article
Abstract: PURPOSE: The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC. MATERIALS AND METHODS: Plasma cfDNA levels were quantified by quantitative real-time PCR at six different time-points (before treatment, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 24 weeks) in 18 metastatic cRCC patients receiving sorafenib, as assessed by CT examination according to RECIST 1.1. RESULTS: A …significantly lower plasma cfDNA level, measured from 8 weeks to 24 weeks, was found in patients with remission or stable disease than in those with progression. Higher levels in plasma cfDNA levels during the course of treatment indicated poor outcome. For predicting progression, a sensitivity of 66.7% was achieved at 100% specificity using cfDNA levels at 8 weeks. CONCLUSIONS: Monitoring of plasma cfDNA levels during the course of sorafenib therapy could identify metastatic cRCC patients who are likely to exhibit a poor response at an early stage. Show more
Keywords: Cell-free DNA, sorafenib, response, metastatic clear cell renal cell carcinoma
DOI: 10.3233/DMA-120950
Citation: Disease Markers, vol. 34, no. 2, pp. 105-111, 2013
Authors: Lee, Ihn Suk | Lee, Ju Hee | Kim, Hyun Jin | Lee, Jae Min | Lee, Seong Kyu | Kim, Hye Soo | Lee, Jong Min | Park, Kang Seo | Ku, Bon Jeong
Article Type: Research Article
Abstract: BACKGROUND: The identification and characterization of the gene, ERRFI1, in diabetes has not been reported. In this study, we evaluated the relationship between ERRFI1 polymorphism and characteristics of type 2 diabetes mellitus (T2DM) in Korea. SUBJECTS AND METHODS: We conduct a case-control study involving T2DM patients (n=342) and controls (n=473). RESULTS: A novel single nucleotide ERRFI1 gene polymorphism at +807(T/G) was found. G genotype frequency was 40.1% in the diabetic group and 42.7% …in the control group; the difference was not significant (p=0.45). In the diabetic group, the urine albumin to creatinine ratio (ACR) was lower in the G genotype than in the T genotype (P=0.004). In males with T2DM, those with the G genotype displayed lower systolic blood pressure (P=0.01) and higher glomerular filtration rate (P=0.048) compare to those with the T genotype. In females with T2DM, urine ACR was low in those with the G genotype than in those with the T genotype (P=0.02). In the diabetic group, patients who harboring T allele had a 1.81 times higher risk of diabetic nephropathy than the G allele (95% CI 1.11–2.96, P=0.02). In females with T2DM, patients who harboring T allele had a 2.12 times higher risk of diabetic nephropathy (95% CI 1.07–4.1, P=0.03). CONCLUSIONS: We identify new loci associated with glycemic traits in diabetes and this finding indicates the potential of ERRFI1 as a novel therapeutic target of diabetic nephropathy. Show more
Keywords: Diabetic nephropathy, ERRFI1, polymorphism, type 2 diabetes
DOI: 10.3233/DMA-120949
Citation: Disease Markers, vol. 34, no. 2, pp. 113-124, 2013
Authors: Baeza-Richer, Carlos | Blanco-Rojo, Ruth | López-Parra, Ana M. | Brichs, Anna | Bertoncini, Stefania | Pérez-Granados, Ana M. | Buil, Alfonso | Soria, José M. | Arroyo-Pardo, Eduardo | Vaquero, M. Pilar
Article Type: Research Article
Abstract: Several iron-related parameters have been reported to show significant heritability, and thus, seemed to be genetically regulated. A genome wide family-based study revealed two regions that showed a linkage signal with transferrin receptor levels. The aim of the study was to identify genetic markers associated with iron status biomarkers. Ten SNPs selected from the literature were tested, and parameters related to iron metabolism were analysed, in a group (n=284) of Spanish women. Data were analyzed using …Bayesian Model Averaging (BMA) test and decision trees. The rs1375515, located in an intronic region of the calcium channel gene CACNA2D3, showed strong associations with levels of mean corpuscular volume according to BMA test, and with levels of haemoglobin and ferritin according to decision trees. The allele G was associated to low levels of these parameters which suggests higher iron deficiency anaemia risk. This SNP along with the C282Y mutation explained significant differences in the distribution of individuals in three iron-related clinical phenotypes (normal, iron deficient and iron deficiency anaemic). In conclusion, the rs1375515, or other genetic polymorphisms in linkage, may play important roles in iron status, probably by affecting the function of a calcium channel. These findings may be useful for further investigation in the etiology of iron diseases. Show more
Keywords: Quantitive trait nucleotype, iron deficiency anaemia, calcium channel gene, SNP, association study
DOI: 10.3233/DMA-120951
Citation: Disease Markers, vol. 34, no. 2, pp. 121-129, 2013
Authors: Ghigliotti, Giorgio | Barisione, Chiara | Garibaldi, Silvano | Brunelli, Claudio | Palmieri, Daniela | Spinella, Giovanni | Pane, Bianca | Spallarossa, Paolo | Altieri, Paola | Fabbi, Patrizia | Sambuceti, Gianmario | Palombo, Domenico
Article Type: Research Article
Abstract: Proinflammatory components are present in abdominal aortic aneurysm (AAA). Circulating monocytes display heterogeneity, and three subsets have been identified, based on the differential expression for CD14 and CD16 receptors: CD14+ CD16- , classical, CD14+ CD16+ , intermediate and CD14dim CD16+ , non-classical monocytes. Increased proinflammatory CD16+ monocytes with high expression of CD143 are present in CKD patients. D-dimer is increased in AAA patients, and might contribute to …the pro-inflammatory response associated to circulating monocytes. We aimed to investigate the frequency of CD14+ CD16+ , CD14dim CD16+ monocytes and monocyte CD143 expression in AAA patients, and their relationship with D-dimer, eGFR and other inflammatory parameters. Blood from 74 AAA patients and 30 healthy controls was analyzed to determine the frequency of CD14+ ULA>CD16+ , CD14dim CD16+ monocytes and the monocyte CD143 expression by means of flow-cytometry. AAA patients had expanded CD16+ SUPsets (CD14+ CD16+ : 7.66 ± 0.31% vs 5.42 ± 0.27%; CD14dim CD16+ : 7.43 ± 0.48% vs 5.54 ± 0.38%, AAA vs controls, mean ± SE, both p< 0.05). CD14+ CD16+ cells were associated to D-dimer and age, and to reduced eGFR. CD14dim} CD16+ cells were associated to uric acid, surface CD143, and reduced count of total leukocytes and neutrophils. Within AAA patients, the two CD16+ SUPsets and the monocyte CD143 expression display different relationships with D-dimer, parameters of renal function and circulating biochemical and inflammatory biomarkers. Show more
Keywords: Monocytes, CD14 antigen, D-dimer, immunoglobulin G receptor, chronic renal failure, angiotensin converting enzyme
DOI: 10.3233/DMA-120956
Citation: Disease Markers, vol. 34, no. 2, pp. 131-142, 2013
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