The diagnostic significance of circulating lncRNA ADAMTS9-AS2 tumor biomarker in non-small cell lung cancer among the Egyptian population.

BACKGROUND: Long non-coding RNA ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9-AS2) was recognized as a novel tumor suppressor and plays an important role in the initiation and progression of malignant behavior in human cancers, although its plasma expression and clinical value in patients with non-small cell lung cancer (NSCLC) remain unknown. We aimed to analyze the diagnostic role of ADAMTS9-AS2 and cytokeratin 19 fragmentation antigen (CYFRA 21-1) in NSCLC. METHODS: The present study included 80 control subjects, 80 patients with benign lung lesion and 80 NSCLC patients. The expression of ADAMTS9-AS2 in the tissue and plasma was detected by a real-time polymerase chain reaction. Serum CYFRA 21-1 was analyzed using an enzyme-linked immunosorbent assay. RESULTS: In comparison with benign lung lesion and controls, tissue and plasma ADAMTS9-AS2 expression were significantly down-regulated in NSCLC (p < 0.001). Decreased ADAMTS9-AS2 expression was associated with TNM stages in NSCLC patients (p < 0.001). Up-regulation of CYFRA 21-1 was reported among NSCLC patients and it was associated with TNM staging. Tissue and plasma ADAMTS9-AS2 expression levels were the predicting factors for NSCLC and they both correlated negatively with CYFRA 21-1 levels. Plasma ADAMTS9-AS2 levels had a significant positive correlation with their tumor tissue levels. Plasma ADAMTS9-AS2 showed a higher sensitivity (95%) and specificity (99.1%) in the diagnosis of NSCLC than CYFRA 21-1 (61.3% sensitivity and 60% specificity). CONCLUSIONS: Our results suggested that decreased plasma ADAMTS9-AS2 expression might act as a novel non-invasive tumor biomarker in NSCLC diagnosis. Furthermore, plasma ADAMTS9-AS2 might predict aggressive tumor behavior.

Circulating miR-181a and miR-223 expression with the potential value of biomarkers for the diagnosis of systemic lupus erythematosus and predicting lupus nephritis.

BACKGROUND: MicroRNAs (miRNAs) contribute to the development and progression of systemic lupus erythematosus (SLE) by affecting a wide range of targeted genes and facilitating the development of lupus nephritis (LN). The present study aimed to analyze the serum expression of miR-181a and miR-223 in SLE patients and to assess whether they could serve as novel biomarkers for SLE diagnosis and to distinguish LN. METHODS: The study included 70 control subjects and 116 patients with SLE (67 non-LN and 49 LN groups). Circulating miR-181a and miR-223 expression levels were analyzed among the Egyptian population using a real-time polymerase chain reaction. RESULTS: Up-regulation of miR-181a was detected among SLE patients compared to healthy controls and higher values were reported among the LN group compared to the non-LN group. Down-regulation of miR-223 was reported among SLE patients compared to controls and lower values were reported among the LN group compared to the non-LN group. The higher miR-181a expression and the lower miR-223 expression were associated with higher stages of LN. SLE disease activity index, proteinuria and serum creatinine were independently correlated with miR-181a and miR-223 among SLE patients by linear regression analysis. Receiver-operating characteristic curve analysis revealed that combined miR-181a and miR-223 expression increased the sensitivity and specificity for the diagnosis of SLE and further distinguished LN from non-LN patients. CONCLUSIONS: miR-181a and miR-223 could play a role in evaluating SLE disease progression and prognosis. Combined miR-181a and miR-223 expression analysis could serve as novel serum-based biomarkers in the diagnosis of SLE and predicting LN among Egyptians.

Combined serum miR-29c and miR-149 expression analysis as diagnostic genetic markers for colorectal cancer.

Circulating miRNAs gathered much interest in cancer research as noninvasive biomarkers. The aim of this study was to analyze the expression of miR-29c and miR-149 among colorectal cancer (CRC) patients and to explore their diagnostic and prognostic potentials in relation to the clinical and pathological features. The expression levels of miR-29c and miR-149 were evaluated in the sera of 80 CRC patients, 80 colorectal adenoma (CRA) patients, and 80 healthy controls using quantitative real time polymerase chain reaction (PCR). Carcinoembryonic antigen serum levels were assayed using enzyme-linked immunosorbent assay. miR-29c and miR-149 were significantly downregulated among CRC patients compared with CRA and controls (miR-29c, 0.54 ± 0.19 vs. 0.86 ± 0.12, 0.99 ± 0.07, P < 0.001, respectively; miR-149, 0.46 ± 0.19 vs. 0.74 ± 0.012, 1.0 ± 0.22, P < 0.001, respectively). miR-29c and miR-149 significantly associated with advanced stages of CRC, tumor size, and lymphatic metastasis. By using receiver operating characteristic curve analysis, combined miR-29c and miR-149 revealed the highest diagnostic potential for CRA (area under the curve [AUC] = 0.967) from healthy controls as well as the diagnosis of CRC (AUC = 0.98) from CRA. Moreover, combined miRNAs revealed high diagnostic potential for the earlier stages of CRC compared with advanced stages (AUC = 0.96). In conclusion, combined serum miR-29c and miR-149 expression analysis established novel noninvasive biomarker for early CRC diagnosis.

The impact of catalase and glutathione peroxidase-1 genetic polymorphisms on their enzyme activities among Egyptian patients with keratoconus.

BACKGROUND: Elevated oxidative stress plays a significant role in pathophysiology of keratoconus (KC). Polymorphisms of the antioxidant enzymes as CAT and GPX-1 might alter their antioxidant enzyme capacities leading to increase in the oxidative damage induced KC. AIM: To analyze the impact of CAT rs7943316 A/T and GPX-1 rs1050450 C/T single nucleotide polymorphisms (SNPs) on the risk and severity of KC among a group of Egyptian population. SUBJECT & METHODS: CAT rs7943316 and GPX-1 rs1050450 SNPs were examined using polymerase chain reaction-restriction fragment length polymorphism in 100 control subjects and 150 KC patients [50 patients (KC stages 1&2), 50 patients (KC stage 3) and 50 patients (KC stage 4)]. RESULTS: Patients with TT genotype of CAT rs7943316 were at high risk of developing KC. T allele of GPX-1 rs1050450 was significantly associated with KC risk (P ˂0.001). The frequency of CAT TT genotype and T allele was significantly higher among severe stages of KC compared to mild and moderate stages. GPX-1 T allele frequency was significantly higher among severe stages of KC compared to mild and moderate stages. A very significant decrease in the antioxidant enzyme activities was observed in association with these SNPs. Age of the patients, CAT and GPX-1 SNPs as well as their enzyme activities were independent predictors of KC severity. CONCLUSION: Our study suggests that CAT (rs7943316) and GPX-1 (rs1050450) SNPs act as independent predictors for different grades of KC and that these SNPs might have a role in the pathogenesis of the disease.

Diagnostic and prognostic value of serum miR-15a and miR-16-1 expression among egyptian patients with prostate cancer.

Prostate cancer (PCa) is considered the most common malignancy in men. The aim of this study is to assess the role of serum miR-15a and miR-16-1 expression in PCa development, diagnosis and prognosis aiming to find a specific noninvasive biomarker. This study comprised 70 patients with PCa, 70 patients complaining of benign prostatic hyperplasia (BPH), 30 patients with chronic prostatitis and 70 controls. Circulating miR-15a and miR-16-1 expression was detected by real-time polymerase chain reaction. Prostate specific antigen levels were measured by enzyme-linked immunosorbent assay. The expression levels of serum miR-15a were decreased in PCa patients compared with controls, chronic prostatitis and BPH patients (0.43 ± 0.12, 1.7 ± 0.76, 1.56 ± 0.34 and 1.53 ± 0.65, respectively). The expression levels of serum miR-16-1 were decreased in PCa patients compared with controls, chronic prostatitis and BPH patients (0.55 ± 0.23, 2.15 ± 0.87, 2.08 ± 0.54 and 1.96 ±0.61, respectively). Downregulation of miR-15a and miR-16-1 correlated with higher Gleason score (P = 0.002 and P = 0.006, respectively), higher tumor stage (P = 0.001 and P = 0.01, respectively), PCa metastasis (P = 0.002 and P = 0.025, respectively) and lymph node involvement (P = 0.02 and P = 0.007, respectively). Moreover, Receiver operating characteristic curve analysis revealed that combined miR-15a/miR-16-1 and PSA increased the sensitivity and specificity for the diagnosis of PCa (97.1% and 94.3%, respectively) more than prostate specific antigen alone (82.9% sensitivity and 75.7% specificity). Combined serum miR-15a/miR-16-1 expression and PSA level can be used as promising specific noninvasive biomarkers in the diagnosis and prognosis of PCa better than prostate specific antigen alone. © 2018 IUBMB Life, 70(5):437-444, 2018.

The association of IL-33 and Foxp3 gene polymorphisms with recurrent pregnancy loss in Egyptian women.

Deregulated immunity is one of the most important factors implicated in recurrent pregnancy loss (RPL). The possible role of interleukin-33 (IL-33) and forkhead/winged helix transcription factor (Foxp3) in RPL have not been fully investigated. We aimed to evaluate IL-33 rs1929992 and Foxp3 rs2232365 single nucleotide polymorphisms (SNPs) and their serum levels in Egyptian RPL females. Blood samples were collected from 142 RPL patients and 123 women as healthy controls. IL-33 rs1929992 SNP was determined by polymerase chain reaction restriction fragment length polymorphism and Foxp3 rs2232365 SNP was determined using allele specific polymerase chain reaction. The serum IL-33 and Foxp3 levels were measured by enzyme linked immunosorbent assay. Foxp3 rs2232365 SNP showed statistically significant association with RPL. The risk of RPL was significantly higher in women carrying Foxp3 G allele than those carrying A allele. Lower serum levels of Foxp3 and IL-33 were observed in RPL patients than controls (P < 0.001). Foxp3 serum levels were much lower in carriers of G allele than those carrying A allele in all studied groups. Foxp3 rs2232365 SNP could be considered as a risk factor for RPL. The lowered serum levels of IL-33 and Foxp3 in RPL patients suggested that they might have an important role in the pathogenesis of the disease. Therefore, we hypothesized that Foxp3 polymorphisms may be important in RPL pathogenesis.

Interferon alpha gene expression and serum level association with low vitamin D levels in Egyptian female patients with systemic lupus erythematosus.

Background Patients with systemic lupus erythematosus (SLE) are prone to develop vitamin D (25(OH) D3) deficiency, due to several factors and there is an association between lower vitamin D levels and higher SLE disease activity. The aim of this research was to assess the prevalence of vitamin D deficiency in Egyptian female patients with SLE. Furthermore, we analyzed the potential relationship between this deficiency and SLE manifestations, disease activity, and its effect on interferon alpha (IFN-α) gene expression and serum level. Methods We evaluated the serum levels of vitamin D 25(OH)D3 and IFN-α by enzyme-linked immunosorbent assay (ELISA). IFN-α gene expression was measured by real-time polymerase chain reaction (PCR) assay in 123 Egyptian female patients with SLE and in 100 females as a healthy control group. Results Vitamin D deficiency was prevalent in 20.30%, while insufficiency was prevalent in 42.40% of the total group of patients. Serum levels of 25(OH)D3 were significantly decreased in the group of severe disease, and in the group of patients with lupus nephritis. 25(OH)D3 showed highly significant negative correlation with the SLE Disease Activity Index (SLEDAI) in the high activity group and lupus nephritis group. There was a significant negative correlation between 25(OH)D3 and IFN-α serum level and gene expression in all patients; more significant in the group with lupus nephritis. Conclusions The deficiency of 25(OH)D3 has a direct relationship with increase disease activity and nephritis in Egyptian SLE patients, suggesting the need for vitamin D supplementation in these patients. Also, it is directly correlated with increased secretion and gene expression of IFN-α, suggesting its role in pathogenesis of lupus nephritis, to be confirmed by further longitudinal observational studies.

ADAM33 and ADAM12 genetic polymorphisms and their expression in Egyptian children with asthma.

BACKGROUND: The ADAM family is involved in some pathologic processes, such as inflammation and asthma. OBJECTIVES: To assess the association between ADAM33 and ADAM12 single-nucleotide polymorphisms (SNPs) with asthma risk and severity and to investigate the effect of ADAM33 and ADAM12 polymorphisms on expression of these proteases in sputum. METHODS: Two SNPs of the ADAM33 gene, F+1 (rs511898) G/A and ST+4 (rs44707) A/C, and 2 SNPs of the ADAM12 gene, rs3740199 and rs1871054, were analyzed in 400 asthma cases and 200 controls aged 3 to 14 years using the polymerase chain reaction-restriction fragment length polymorphism method. Messenger RNA expression profile of ADAM33 and ADAM12 proteases in sputum from studied groups was determined by reverse transcription polymerase chain reaction. RESULTS: ADAM33 F+1 homozygous mutant genotype (AA) and ST+4 heterozygous and homozygous mutant genotype (AC and CC) and mutant alleles of both polymorphisms were significantly associated with asthma risk and severity in moderate and severe subgroups. Patients with the ADAM12 (rs3740199) CC genotype were at increased risk for moderate and severe asthma. Messenger RNA levels of ADAM12 were significantly increased in asthmatic children compared with controls, whereas we were not able to detect the expression of ADAM33 in the sputum of the groups studied. The ADAM12 expression was significantly higher in homozygous CC (variant type) compared with homozygous GG (wild type) of both ADAM12 rs3740199 and rs1871054 in the asthmatic group. CONCLUSION: Our analysis suggests a likely role for ADAM33 and ADAM12 in the development of asthma in Egyptian children. Furthermore, ADAM12 polymorphisms may affect ADAM12 expression in asthma.

The therapeutic prospect of zinc oxide nanoparticles in experimentally induced diabetic nephropathy.

Diabetic nephropathy (DN) is the most frequent cause of end-stage renal failure. Zinc oxide nanoparticles (ZnO-NPs) are promising antidiabetic agents. Our aim was to evaluate the prospective efficacy of ZnO-NPs in treating DN in streptozotocin-induced diabetic rats. Rats were randomly dispersed into three sets: control group, DN group and DN + ZnO-NPs group. ZnO-NPs were given at a dose of 10 mg/kg/day by oral gavage for 4 weeks. Urine and blood samples were processed for biochemical analyses. Kidney samples were managed for light and electron microscopy studies. Immune histochemical staining of P53, aquaporin11 (AQP11) and mechanistic target of rapamycin (mTOR) were performed. Gene analyses of nephrin, podocin, beclin-1, LC3 and p62 were done. Administration of ZnO-NPs ameliorated the functional and histopathological alterations of the kidney in a rat model of diabetic nephropathy. ZnO-NPs retained the constancy of the glomerular filtration barrier and restored almost normal renal structure. This was confirmed by upregulation of mRNA expression of podocyte markers (nephrin and podocin) and AQP11 immune histochemical expression in the renal tubules. The beneficial outcomes of ZnO-NPs might be attributed to activation of autophagy through inhibiting mTOR signaling pathway. ZnO-NPs enhanced beclin-1 and LC3 mRNA expressions and reduced p62 mRNA expression. ZnO-NPs also exerted anti-apoptotic potential (evidenced by the decrease in p53 immune expression), anti-inflammatory and anti-oxidant effect [endorsed by suppression of serum cyclooxygenase-2 (COX-2) enzyme activity, tissue nuclear factor kappa beta (NF-κB) level and blood hypoxia-inducible factors (HIF-1α) level]. These results may point the way to an effective therapy of DN.Abbreviations: AQP11 Aquaporin11; BUN: Blood urea nitrogen; COX-2: Cyclooxygenase-2; DAB: 3, 3'-diaminobenzidine; DM: Diabetes mellitus; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; H&E: Hematoxylin & eosin; HIF-1α: Hypoxia-inducible factors; iNOS: inducible nitric oxide synthase; LC3: Microtubule-associated protein 1 light chain 3; mTOR: Mechanistic target of rapamycin; NF-κB: Nuclear factor kappa beta; NPs: Nanoparticles; PAS: Periodic acid Schiff; PCR: Polymerase chain reaction; PGE2: Prostaglandin E2; ROS: Reactive oxygen species; STZ: Streptozotocin; X ± SEM: Mean ± standard error of means; Zn: Zinc; ZnO-NPs: Zinc oxide nanoparticles.

GLP-1R polymorphism (rs1042044) and expression are associated with the risk of papillary thyroid cancer among the Egyptian population.

BACKGROUND: Glucagon like peptide-1 receptor (GLP-1R) agonist usage has previously been linked to an elevated incidence of thyroid cell adenomas and carcinomas in animals. AIM: The goal of this study was to determine if there was an association between GLP-1R gene polymorphism and expression with the risk of papillary thyroid carcinoma (PTC) and its clinical characteristics among the Egyptian population. MATERIAL AND METHODS: A total of eighty PTC patients and eighty healthy controls were included in the study. Real-time polymerase chain reaction (real-time PCR) and immunohistochemistry were used to determine GLP-1R expression in tumor tissue. The polymorphisms rs1042044 and rs6923761 in the GLP-1R gene were determined using PCR -restriction fragment length polymorphism (PCR-RFLP). RESULTS: PTC patients exhibited considerably greater frequencies of rs1042044 AA genotypes and A allele than controls (OR (95% CI) = 4.5 (1.75-11.8), P < 0.001; OR (95% CI) = 2.032 (1.301-3.17), P < 0.001 respectively). GLP-1R mRNA and protein expressions were higher in tumor samples than normal thyroid tissues among PTC patients. In addition, high GLP-1R expressions were more common in rs1042044 AA genotype carriers than CC carriers (P < 0.001). GLP-1R mRNA expression showed 95 % sensitivity and 97% specificity for PTC diagnosis. Moreover, GLP-1R expression was closely associated with LN metastasis, tumor size, tumor stage, and multifocality in PTC patients. CONCLUSION: This research provides new evidence linking the GLP-1R genetic polymorphism and tissue expression to PTC risk and invasiveness among the Egyptian population.

Mesna ameliorates acute lung injury induced by intestinal ischemia-reperfusion in rats.

The lung is severely affected by intestinal ischemia-reperfusion (I-R) injury. Mesna, a thiol compound, possess anti-inflammatory and antioxidant properties. We aimed in the present work to explore the potential beneficial effects of Mesna on the acute lung damage mediated by intestinal I-R in a rat model. Forty male adult albino rats were randomly separated into; control, intestinal I-R, Mesna I and Mesna II groups. Mesna was administered by intraperitoneal injection at a dose of 100 mg/kg, 60 min before ischemia (Mesna I) and after reperfusion (Mesna II). Arterial blood gases and total proteins in bronchoalveolar lavage (BAL) were measured. Lung tissue homogenates were utilized for biochemical assays of proinflammatory cytokines and oxidative stress markers. Lung specimens were managed for examination by light and electron microscopy. Our results revealed that Mesna attenuated the histopathological changes and apoptosis of the lung following intestinal I-R. Mesna also recovered systemic oxygenation. Mesna suppressed neutrophil infiltration (as endorsed by the reduction in MPO level), reduced ICAM-1 mRNA expression, inhibited NF-κB pathway and reduced the proinflammatory cytokines (TNF-α, IL-1ß and IL-6) in the lung tissues. Mesna maintained the antioxidant profile as evidenced by the elevation of the tissue GPx and SOD and down-regulation of HSP70 immune-expressions. Accordingly, Mesna treatment can be a promising way to counteract remote injury of the lung resulted from intestinal I-R.

Interferon-gamma Expression Profile as Diagnostic Signatures of Unexplained Infertility in Female Patients Suffer from Hashimoto's Thyroiditis.

Diagnosis of unexplained infertility (UEI) is made by exclusion and a relatively common problem that affects couples worldwide. Unfortunately, it is a not uncommon for females to suffer from Hashimoto's thyroiditis (HT). Interferon-gamma (IFN- γ) has a central key role in HT and in the ability to conceive. We aimed to estimate serum IFN- γ level and its expression profile in Egyptian women with HT and assess their possible association with UEI. In this study, we examined 120 women with HT. We evaluated fertility in all patients; female patients who suffer from UEI were detected. Diagnosis of HT was based on the clinical data and the laboratory measures, enzyme-linked immunosorbent assay was used to measure serum IFN- γ, and the expression of IFN-γ messenger ribonucleic acid (mRNA) was assayed by real-time polymerase chain reaction (PCR). According to the results of this study, 37.5 % of the studied females who suffered from HT were diagnosed with UEI. The serum level of IFN-γ and its gene expression showed a significant positive correlation with thyroid-stimulating hormone (TSH) and thyroid autoantibodies. However, a negative correlation was found with anti-müllerian hormone (AMH), free T4 (FT3), and free T4 (FT4). Analysis by linear regression revealed that TSH and FT3 were associated with serum level of IFN-γ; while FT3 was associated with IFN-γ gene expression. We concluded that both are valued markers in diagnosing UEI in female patients suffering from HT.

Visfatin and SREBP-1c mRNA Expressions and Serum Levels Among Egyptian Women with Polycystic Ovary Syndrome.

Background: Obesity and insulin resistance are common features accompanying polycystic ovary syndrome (PCOS). Aim: To analyze the impact of obesity on the expression of the visfatin and sterol regulatory element-binding protein (SREBP)-1c genes among a group of Egyptian women with PCOS, and to assess their suitability as PCOS biomarkers. Subject and methods: Seventy healthy women (control group) (35 nonobese and 35 obese) and 140 women with PCOS (70 nonobese and 70 obese) were enrolled in this study. The visfatin and SREBP-1c genes' expression analyses were performed via real-time polymerase chain reaction. Serum visfatin and SREBP-1c protein levels were measured with ELISA kits. Results: Among PCOS patients, upregulation of visfatin and SREBP-1c expression was observed. We did not identify significant differences between the obese and nonobese PCOS patients nor between obese and non-obese controls. The mRNA expression levels of both genes were significantly positively correlated with their serum protein levels, as well as with fasting serum insulin levels, homeostatic model assessments of insulin resistance (HOMA-IR), luteinizing hormone (LH) ratios, LH/follicular stimulating hormone ratios, total testosterone, and free androgens. We observed significant negative correlations between visfatin and SREBP-1c expression levels and sex hormone binding globulin levels in all studied groups. Receiver operating characteristic curve analyses revealed that combining the visfatin and SREBP-1c expression data increased the sensitivity (95.92%) and specificity (93.2%) for PCOS diagnoses. Conclusion: Upregulation of visfatin and SREBP-1c was observed among PCOS patients. These genes may play a role in the pathogenesis of PCOS independent of obesity. Combined visfatin and SREBP-1c analyses could be used as a noninvasive biomarker for PCOS.

Cellular, Molecular and Biochemical Impacts of Silver Nanoparticles on Rat Cerebellar Cortex.

BACKGROUND: The excessive exposure to silver nanoparticles (Ag-NPs) has raised concerns about their possible risks to the human health. The brain is a highly vulnerable organ to nano-silver harmfulness. The aim of this work was to evaluate the impacts of Ag-NPs exposure on the cerebellar cortex of rats. METHODS: Rats were assigned to: Control, vehicle control and Ag-NP-exposed groups (at doses of 10 mg and 30 mg/kg/day). Samples were processed for light and electron microscopy examinations. Immunohistochemical localization of c-Jun N-terminal kinase (JNK), nuclear factor kappa beta (NF-κB) and calbindin D28k (CB) proteins was performed. Analyses of expression of DNA damage inducible transcript 4 (Ddit4), flavin containing monooxygenase 2 (FMO2) and thioredoxin-interacting protein (Txnip) genes were done. Serum levels of inflammatory cytokines were also measured. RESULTS: Ag-NPs enhanced apoptosis as evident by upregulation of Ddit4 gene expressions and JNK protein immune expressions. Alterations of redox homeostasis were verified by enhancement of Txnip and FMO2 gene expressions, favoring the activation of inflammatory responses by increasing NF-κB protein immune expressions and serum inflammatory mediator levels. Another cytotoxic effect was the reduction of immune expressions of the calcium regulator CB. CONCLUSION: Ag-NPs exposure provoked biochemical, cellular and molecular changes of rat cerebellar cortex in a dose-dependent manner.

The influence of glyoxalase 1 gene polymorphism on its expression at different stages of breast cancer in Egyptian women.

AIM: To assess the association of GLO1 C332C gene polymorphism with breast cancer risk at different stages of the disease and to investigate the effect of this gene polymorphism on its mRNA expression and enzyme activity. METHODS: GLO1 C332C gene polymorphism was analyzed by PCR-RFLP in 100 healthy controls and 200 patients with breast cancer (100 patients with stage I & II and 100 patients with stage III & IV). GLO1 mRNA expression was measured by real time PCR. Serum GLO1 enzyme activity was measured colorimetrically. RESULTS: GLO1 A allele was associated with increased risk of breast cancer [OR (95%CI)= 2.8(1.9-4.1), P < 0.001]. Its frequency was significantly higher among advanced stages of breast cancer compared with localized tumors (OR (95%CI)= 1.9(1.3-2.9), p < 0.001). GLO1 mRNA expression and enzyme activity were significantly higher in breast cancer patients compared to controls and they were much higher in the advanced stages of the disease (P < 0.001). Carriers of AA genotype showed higher GLO1 expression and enzyme activity compared with carriers of CC genotype. CONCLUSION: GLO1 C332C SNP was associated with overexpression of GLO1 mRNA and higher enzyme activity in breast cancer patients suggesting its role in the development of breast cancer and its progression from localized to advanced.

Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer.

BACKGROUND: Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. OBJECTIVES: The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. PATIENTS AND METHODS: The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. RESULTS: The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (P<0.001 for each). Analysis of their expression showed that levels of FGFR1 and CK20 were significantly higher in invasive tumor stages (pT2-pT4) than in non-invasive stages (pTis, pTa, pT1) (P<0.001). Interestingly, the sensitivity and specificity of combined detection with CK20 and FGFR1 for the differentiation between invasive and non-invasive stages of bladder cancer reached 97.5% and 92.5%, respectively. CONCLUSION: Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma.