Cancer Biomarkers - Volume 12, issue 4-5

Authors: El-Hafez, Amal Abd | Shawky, Abd El Aaty | Hasan, Basem

Article Type: Research Article

Abstract: Background: Strong evidence implicates cyclin D1 in human breast cancer. Nevertheless, the prognostic value of cyclin D1 overexpression in breast cancer is still controversial. This work aims to assess the predictive value of cyclin D1 immunohistochemical expression in invasive breast carcinomas and evaluate its association with clinicopathological parameters, in addition to hormone receptor status and Her2/neu immunohistochemical expression. Materials and Methods: This study was conducted on 71 cases of invasive breast carcinoma selected according to the availability of clinical data and paraffin-embedded tissue specimens. Immunohistochemistry was performed for estrogen receptors (ER); progesterone receptors (PR); Her2/neu and cyclin D1. …Cyclin D1 expression was assessed and compared to the patients’ age, tumor histology, grade, nodal status, tumor size and ER; PR; Her2/neu immunostaining results. Results: Cyclin D1 nuclear expression was detected in 35% of invasive breast carcinomas. There were statistically significant associations between the cyclin D1 and younger age, small tumor size, negative nodal status, well differentiated and lobular types of breast cancer and estrogen receptor positivity. Cyclin D1 had no association with progesterone receptor or Her2/neu. Conclusion: Cyclin D1 immunohistochemical expression associates strongly with the approved favourable prognostic factors in primary breast carcinoma, suggesting a favourable predictive value of cyclin D1. Show more

Keywords: Cyclin D1, breast carcinoma, immunohistochemistry, prognostic factors, hormone receptor, Her2

DOI: 10.3233/CBM-130303

Citation: Cancer Biomarkers, vol. 12, no. 4-5, pp. 149-154, 2013

Authors: Zhang, Chunlin | Zhao, Yao | Zeng, Bingfang

Article Type: Research Article

Abstract: Aim: To investigate whether the inhibition of Bcl-2 and Cyclin D1 by lentivirus-mediated RNA interference enhances doxorubicin (DXR) cytotoxicity in the drug-resistant human osteosarcoma MG63 cells. Materials and Methods: Lentivirus-mediated RNAi were used to inhibit the expression of Bcl-2 or Cyclin D1 mRNA and protein; qRT-PCR, Western blotting, Flow cytometry and MTT assays were used to detect the expression of Bcl-2 and Cyclin D1 and the sensitivity to doxorubicin of MG63/DXR. Results: Chronic exposure to DXR induces upregulation of oncogenic Bcl-2 and CyclinD1 in osteosarcoma MG63/DXR cells. Elevated Bax and decreased cyclin D1 was observed in …Bcl-2-silenced MG63/DXR cells and decreased Bcl-2 was detected in Cyclin D1-silenced MG63/DXR cells. Individual or simultaneous silencing of Bcl-2/Cyclin D1 enhanced the cytotoxicity of DXR. Furthermore, we detected a synergistic effect of enhanced chemosensitivity by co- silencing Cyclin D1 and Bcl-2. Conclusion: Lentiviral RNAi targeting of Bcl-2 and Cyclin D1 simultaneously could be a potentially more effective therapeutic strategy for osteosarcomas to overcome chemoresistance. Show more

Keywords: Osteosarcoma, chemoresistance, RNA interference, Bcl-2, Cyclin D1

DOI: 10.3233/CBM-130305

Citation: Cancer Biomarkers, vol. 12, no. 4-5, pp. 155-167, 2013

Authors: Zou, Zhi-Jian | Fan, Lei | Wang, Li | Zhang, Run | Zhang, Li-Na | Yang, Shu | Li, Jian-Yong | Xu, Wei

Article Type: Research Article

Abstract: Background: Carbohydrate antigen 125 (CA-125) is a glycoprotein produced by epithelial and mesothelial cells. Serum CA-125 can be elevated in many benign and malignant conditions in which these tissues are involved. Methods: We measured serum CA-125 concentration in 112 patients with chronic lymphocytic leukemia (CLL) and evaluated their association with Binet stage, serum lactate dehydrogenase (LDH), beta2-microglobulin (β2-MG), CD38, 70-kDa zeta-associated protein (ZAP-70), immunoglobulin heavy-chain variable region (IGHV) mutated status and cytogenetic abnormalities. Results: The high level of CA-125 was associated with advanced Binet stage (r=0.463, p< 0.001), high level of LDH (r=0.404, p< 0.001) and …β2-MG (r=0.274, p=0.004), and unmutated IGHV status (r=0.366, p=0.009). Multivariate analysis showed that advanced Binet (p<0.001) and unmutated IGHV status (p=0.018) were risk factors for the high CA-125 level. In univariate analysis, treatment-free survival (TFS) and overall survival (OS) were affected by Binet stage (p<0.001 and p=0.042, respectively), LDH (p=0.018 and p=0.013, respectively), β2-MG (p=0.006, TFS only), ZAP-70 (p=0.031, OS only), CD38 (p=0.003, OS only), the presence of del(17p13) or del(11q22.3) (p=0.006 and p=0.049, respectively), IGHV mutation status (p=0.018 and p< 0.001, respectively) and CA-125 (p=0.003 and p=0.034, respectively). In multivariate analysis, only advance Binet stage (p<0.001) was independent risk factor of shorter TFS. CD38-positive (p=0.020) and unmutated IGHV status (p=0.034) were independent risk factors of worse OS. Conclusions: The results support a high CA-125 level correlates significantly with many clinical features of advanced stage, poor prognostic factors, and worse TFS and OS. However, CA-125 is not an independent prognostic factor in patients with CLL. Show more

Keywords: CA-125, chronic lymphocytic leukemia, prognosis

DOI: 10.3233/CBM-130304

Citation: Cancer Biomarkers, vol. 12, no. 4-5, pp. 169-176, 2013

Authors: Joseph, Sasha | Harrington, Ryan | Walter, Dawn | Goldberg, Judith D. | Li, Xiaochun | Beck, Amanda | Litton, Tyler | Hirsch, Nathalie | Blasberg, Justin | Slomiany, Mark | Rom, William | Pass, Harvey | Donington, Jessica

Article Type: Research Article

Abstract: Introduction: As CT screening is integrated into non-small cell lung cancer (NSCLC) care, additional parameters are needed to help distinguish cancers from benign nodules. Osteopontin (OPN), a secreted phosphoprotein, has elevated plasma levels in NSCLC. We hypothesize that changes in plasma OPN over time (i.e., OPN velocity [OPNV]) can differentiate NSCLC patients from those without cancer in a CT screening population. Methods: A nested case-control study was conducted within a NSCLC CT screening trial. Incident cancers with serial plasma were matched to controls. OPN was measured by ELISA. Demographic, OPN, and OPNV were compared between cancers and controls …using Wilcoxon Signed Rank tests. Results: Ten incident cancers were identified. The pack years distributions were similar, but cancers were older (median of the paired difference: 5.35 years; p=0.002) and their surveillance intervals were shorter (median of the paired difference: −2 months; p=0. 03) than matched controls. Baseline OPN was similar (median of the paired difference: −5.15 ng/ml, p=0.50), but OPNV in the cancers was significantly greater than that of matched controls, (median of the paired difference: 1.06 ng/ml/month, p=0.01). Accuracy rate for prediction of disease status based on OPNV (adjusted for age and surveillance) was 83%. Conclusions: These are early evidence for utility of monitoring plasma OPN during CT screening to assist in identification of NSCLCs. Show more

Keywords: Non-small cell lung cancer, osteopontin, biomarker, early detection, CT screening

DOI: 10.3233/CBM-130306

Citation: Cancer Biomarkers, vol. 12, no. 4-5, pp. 177-184, 2013

Authors: Lim, Shi Rou | Gooi, Boon-Hui | Gam, Lay Harn

Article Type: Research Article

Abstract: Background: Detection of low abundance proteins always possesses challenges even with the currently available proteomics technologies. Objective: We aimed to evaluate the low abundance differentially expressed proteins in colorectal cancerous tissues as compared to colorectal normal tissues. Methodology: Protein separation was carried out by using the coupling methods of hydroxyapatite chromatography and SDS-PAGE followed by mass spectrometry analysis. Results: Five of the membrane associated low abundance proteins, namely uncharacterized protein C5orf4, coiled-coil domain containing protein 152, DnaJ homolog subfamily C member 22, tumor suppressor candidate 3 and leucine-rich repeat transmembrane neuronal protein 4 that …previously only reported at the genome level were identified. Conclusions: The proteins were isolated from the cancerous tissues as either up-regulated or down-regulated proteins as compared to normal tissues and therefore may play important roles in cancer development. Show more

Keywords: Low abundance proteins, colon cancer, proteomics, tissue specimens human colonic tissues, hydroxyapatite chromatography fractionation, SDS-PAGE, mass spectrometer

DOI: 10.3233/CBM-130307

Citation: Cancer Biomarkers, vol. 12, no. 4-5, pp. 185-198, 2013

Authors: Faltejskova, Petra | Bocanek, Ondrej | Sachlova, Milana | Svoboda, Marek | Kiss, Igor | Vyzula, Rostislav | Slaby, Ondrej

Article Type: Research Article

Abstract: Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Therefore, there is a high demand for cost-effective and non-invasive biomarkers that would enable an early detection of asymptomatic and curable disease with high sensitivity and specificity. Objective: The main objective of this study was to investigate the potential of circulating miRNAs as biomarkers of CRC. Methods: Total RNA enriched for small RNAs was isolated from 100 sera of patients with CRC and 30 sera of healthy donors. The expression levels of miR-17-3p, miR-29a, miR-92a and miR-135b were determined using quantitative …real-time PCR. The average expression levels of particular miRNAs were normalized to miR-16 levels and statistically evaluated. Results: Using Mann-Whitney U test, no significant differences were observed in miR-17-3p (P=0.18), miR-29a (P=0.14) and miR-92a (P=0.60) levels between sera of CRC patients and controls. The levels of miR-135b in serum were too low to be quantified accurately. Subsequently, we tried to correlate expression levels of analyzed miRNAs to clinical-pathological features of CRC patients. Only levels of mir-29a were correlated with the clinical stage (P=0.04). Expression levels of the other miRNAs were correlated neither with the clinical stage, nor with the grade. Conclusions: Interestingly, our results are contradictory to previous studies performed on the CRC patients from Chinese population, providing an evidence against usage of serum miR-17-3p, miR-29a, miR-92a and miR-135b as new biomarkers for early detection of CRC. Show more

Keywords: microRNAs, serum, colorectal cancer, biomarkers

DOI: 10.3233/CBM-130308

Citation: Cancer Biomarkers, vol. 12, no. 4-5, pp. 199-204, 2013