Disease Markers - Volume 34, issue 6

Authors: He, Jing | Zhang, Fengmei | Wu, Ying | Zhang, Wei | Zhu, Xiaoli | He, Xuelian | Zhao, Yuhang | Zhang, Wei | Zhao, Yulan

Article Type: Research Article

Abstract: BACKGROUND: Recent studies have shown that microRNAs (miRNA) have prognostic values in cancers. This meta-analysis seeks to summarize the global predicting role of miR-155 for survival in patients with a variety of carcinomas. METHODS: Eligible studies were identified through multiple search strategies. Data were extracted from studies investigating the relationship between miR-155 expression and survival in cancer patients. Combined hazard ratios (HRs) of miR-155 for outcome were analyzed. RESULTS: A total of …16 studies dealing with various carcinomas were included for this meta-analysis. For overall survival, higher miR-155 expression could significantly predict worse outcome with the pooled HR of 2.057 (95% CI: 1.392–3.039). For relapse or progress-free survival, elevated miR-155 was also a significant predictor, with a combined HR of 1.918 (95% CI: 1.311–2.806,). In addition, subgroup analysis showed that higher expression of miR-155 had the trends to predict worse outcome in lung cancer. However, the HRs did not reach the statistical significance. CONCLUSION: Our findings suggest that miR-155 detection has a prognostic value in cancer patients. Regularly measuring miR-155 expression may be useful in clinical practice. Show more

Keywords: miR-155, cancer, prognosis, clinical

DOI: 10.3233/DMA-130984

Citation: Disease Markers, vol. 34, no. 6, pp. 379-386, 2013

Authors: Taheri, Mohsen | Mahjoubi, Frouzandeh

Article Type: Research Article

Abstract: A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well …as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor. Show more

Keywords: Multidrug resistance, real time PCR, breast cancer, MDR1, MRP1

DOI: 10.3233/DMA-130985

Citation: Disease Markers, vol. 34, no. 6, pp. 387-393, 2013

Authors: Benson, Chellakkan Selvanesan | Babu, Somasundaram Dinesh | Radhakrishna, Selvi | Selvamurugan, Nagarajan | Sankar, Bhaskaran Ravi

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal …breast tissues. PATIENTS AND METHODS: We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. RESULTS: The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. CONCLUSION: Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target. Show more

Keywords: Matrix metalloproteinase, cancer grade, breast cancer, matrix degradation, diagnostic marker

DOI: 10.3233/DMA-130986

Citation: Disease Markers, vol. 34, no. 6, pp. 395-405, 2013

Authors: AbdRaboh, Naglaa R. | Shehata, Hanan H. | Ahmed, Manal B. | Bayoumi, Fatehia A.

Article Type: Research Article

Abstract: BACKGROUND: Polymorphism of the genes of Human Epidermal growth factor receptor1 (HER1) and receptor2 (HER2) have been reported to be linked to pathogenesis of several malignant tumors but still there is contradiction regarding their association with breast cancer. OBJECTIVE: In this case control study we aimed to analyze the frequency of HER1 R497K (rs 11543848) and HER2 I655V (rs 1136201) Polymorphisms in breast cancer. SUBJECT AND METHOD: The frequency of HER1 Arg(R) 497Lys (K) and HER2 …Ile (I) 655Val (V) polymorphisms were tested in 64 breast cancer patients and 86 normal control by polymerase chain reaction followed by restriction fragment polymorphism detection. Immunohistochemical analysis was done for HER2 protein on the available 18 malignant tissue samples. RESULTS: HER1 497K and HER2 655V variant had significantly increased breast cancer risk (OR=2.6, 95% CI 1.6–4.2, OR=2.2, 95% CI 1.2–4.1, p< 0.05) respectively. Moreover, combined HER1 K497 and HER2 V655 variant was detected in 26.6% malignant in comparison to 8.14% of control group (OR=4.1, 95% CI 1.58–10.57), but, no significant association was noticed between both Polymorphisms and clinicopathological features of the disease. As regard HER2 immunohistochemical expression no significant correlation was revealed with HER2 655V polymorphism. CONCLUSIONS: our findings suggest that HER1 497K and HER2 655V polymorphisms are potential risk factor for development of breast cancer. Show more

Keywords: HER1 gene, HER2 gene, polymorphism, HER2 protein expression, breast cancer

DOI: 10.3233/DMA-130989

Citation: Disease Markers, vol. 34, no. 6, pp. 407-417, 2013

Authors: Palma, Icela | Garibay, Nayely | Pena-Yolanda, Rocio | Contreras, Alejandra | Raya, Atlantida | Dominguez, Carolina | Romero, Mirna | Aristi, Gerardo | Queipo, Gloria

Article Type: Research Article

Abstract: BACKGROUND: Gonadoblastoma (GB) is regarded as an in situ form of germ cell tumor in dysgenetic gonads, and 30% of patients with GB develop a dysgerminoma/seminoma tumor. OBJECTIVE: Determine whether OCT3/4 and β-catenin are expressed in dysgenetic gonads before GB development and whether TSPY participates in the OCT3/4-β-catenin pathways in the malignant invasive behavior. METHODS: dysgenetic gonads of Disorders of sex differentiation (DSD) patients with mixed gonadal dysgenesis were analyzed by immunohistochemistry …and immunofluorescence for comparison with GB and dysgerminoma/seminoma. RESULTS: Our results suggest that the development of GB is secondary to the interaction of OCT3/4 and TSPY, that β-catenin does not participate in this process. CONCLUSIONS: The use of this biological markers detects the potential high risk gonads. Show more

Keywords: Gonadoblastoma, OCT3/4 , TSPY , β-catenin , dysgenetic gonads, mixed gonadal dysgenesis

DOI: 10.3233/DMA-130972

Citation: Disease Markers, vol. 34, no. 6, pp. 419-424, 2013

Authors: Sánchez-Otero, Nuria | Blanco-Prieto, Sonia | Vázquez-Iglesias, Lorena | Cadena, María Páez de la | Fernández-Villar, Alberto | Botana-Rial, María Isabel | Rodríguez-Berrocal, Francisco Javier

Article Type: Research Article

Abstract: Anti-tumor properties assigned to PEDF, beside its role as an inhibitor of angiogenesis, make it a promising candidate in the search of new biomarkers for malignancy. In this study levels of PEDF were investigated in pleural effusions from lung adenocarcinoma and benign inflammatory disease patients. The mean PEDF concentration in the malignant group was slightly superior to that in patients suffering benign diseases (4.59 μ g/mL vs 3.97 μg/mL), although the difference did not reach statistical …significance (P 0.166). Pleural effusion PEDF levels were not related to gender, age, smoking habit or pleural effusion size. We also investigated the possible relationship of PEDF levels in pleural effusion regarding clinicopathological features. Correlations were found for monocytes (P 0.010) and polymorphonuclear leukocytes (P 0.023) with PEDF levels in pleural effusion of malignant origin. Show more

Keywords: PEDF, pleural effusion, biomarkers

DOI: 10.3233/DMA-130990

Citation: Disease Markers, vol. 34, no. 6, pp. 425-430, 2013

Authors: Zigra, Aggeliki-Maria | Rallidis, Loukianos S. | Anastasiou, Georgia | Merkouri, Efrossyni | Gialeraki, Argyri

Article Type: Research Article

Abstract: BACKGROUND: Endothelial nitric oxide synthase (eNOS) as well as nitric oxide play an important role in the regulation of cardiovascular function. There are limited and controversial data regarding the impact of polymorphisms of eNOS gene that is implicated in the vasoconstrictive properties of the endothelium in the pathogenesis of premature myocardial infarction (MI). OBJECTIVE: We examined whether two common polymorphisms of eNOS gene (G894T and T786C) are associated with the development of premature MI. …METHODS: We recruited 107 patients with premature MI and compared them to 103 age- and sex- matched controls. All patients underwent coronary angiogram and were classified into the subgroup of patients with 'normal' or 'near normal' coronary arteries and the subgroup of patients with significant coronary artery disease (⩾ 50% stenosis in lumen diameter of coronary arteries). The genetic polymorphisms of eNOS gene were assayed with polymerase chain reaction and reverse hybridization. RESULTS: Nineteen patients (17.8%) had 'normal' or 'near normal' coronary arteries. A significantly higher frequency of homozygosity for the 786C (32%) and the 894T (21%) alleles of the eNOS gene in patients who develop early MI in the setting of angiographically 'normal' or 'near normal' coronary arteries were found. CONCLUSIONS: Our data suggest that the T786C and the G894T genetic polymorphisms are associated with the development of MI in very young individuals, whose coronary arteries are characterized by very small atheromatic burden. Show more

Keywords: Cardiovascular disease, genetic polymorphisms, early myocardial infarction, endothelial nitric oxide synthase

DOI: 10.3233/DMA-130987

Citation: Disease Markers, vol. 34, no. 6, pp. 431-436, 2013

Authors: Rahimi, Zohreh | Rahimi, Ziba | Shahvaisi-Zadeh, Frahad | Sadeghei, Shieda | Vessal, Mahmood | Yavari, Niloofar

Article Type: Research Article

Abstract: To investigate the possible association between eNOS 4a/b polymorphism and the risk of developing type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) 173 T2DM patients with and without DN and 101 healthy subjects with ethnic background of Kurds were examined for the frequency of eNOS variants using PCR-RFLP method. The frequency of eNOS 4a/b genotypes between T2DM and controls was not significantly difference. Studying eNOS 4a/b variants alone indicated that the presence of eNOS 4a …allele was not associated with the risk of developing DN. However, considering both polymorphisms of eNOS 4a/b and G894T indicated that the risk of macroalbuminuria significantly increased in the presence of either eNOS 4a or 894T allele by 2.45 times (p=0.014) and 3.7-fold (p=0.016), respectively. However, the concomitant presence of both alleles was not associated with the risk of macroalbuminuria. In microalbuminuric patients, in the presence of each allele, the risk of microalbuminuria increased 2.2 times (p=0.028) and 2.72-fold (p=0.057) for eNOS 4a and 894T alleles, respectively. However, the combined presence of both eNOS 894T and 4a alleles was not associated with the risk of microalbuminuria. The present study indicates the absence of association between eNOS 4a/b variants and the risk of developing T2DM and DN. Also, we demonstrated that eNOS 4a or 894T allele alone increased the risk of developing DN but this effect was modified by the concomitant presence of both alleles. Show more

Keywords: T2DM, eNOS variants, diabetic nephropathy, Western Iran

DOI: 10.3233/DMA-130988

Citation: Disease Markers, vol. 34, no. 6, pp. 437-443, 2013

Authors: Affandi, Jacquita S. | Kumar, Manoj | Agarwal, Upasna | Singh, Sarman | Price, Patricia

Article Type: Research Article

Abstract: BACKGROUND: Up to 43% of HIV-infected patients co-infected with Mycobacterium tuberculosis experience exacerbations of tuberculosis (TB) after commencing antiretroviral therapy (ART). These are termed immune restoration disease (IRD). It is unclear why individual susceptibility varies. OBJECTIVE: We investigate if single nucleotide polymorphisms (SNP) in genes encoding cytokines, chemokines and their receptors associate with development of an IRD event in patients of two different ethnicities. METHODS: DNA samples were available from small well-characterised groups of …HIV patients treated in Cambodia (TB-IRD, n=17; HIV^{+} TB^{+} controls, n=55) and India (TB-IRD, n=19; HIV^{+} TB^{+} controls, n= 43). HIV patients with a TB diagnosis but no evidence of IRD were included to control for susceptibility to TB per se. Sixteen SNP implicated in inflammation or mycobacterial disease were genotyped. RESULTS: Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964; P=0.05) and SLC11A1 D543N*G (rs17235409; P=0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518; P=0.02) and VDR FokI (F/f)*T (rs10735810; P=0.05) in Indian patients. CONCLUSIONS: Associations between polymorphisms in immune-related genes and TB-IRD were found, but none were common across two ethnicities. Show more

Keywords: TB-IRD susceptibility, immunogenetic factor, single nucleotide polymorphism

DOI: 10.3233/DMA-130991

Citation: Disease Markers, vol. 34, no. 6, pp. 445-449, 2013

Article Type: Other

Citation: Disease Markers, vol. 34, no. 6, pp. 451-456, 2013