Cancer Biomarkers - Volume 18, issue 4

Authors: Yuan, Li-Qun | Chen, Yan-Ming | Sun, Chao | Wang, Zhong-Yong | Wang, De-Lin | Lan, Qing

Article Type: Research Article

Abstract: Previous studies indicate that the triterpene glycoside Actein from the herb black cohosh inhibits growth of human breast cancer cells. This study sought to investigate the effects of Actein on glioma cell growth and explore the potential mechanisms. Our results showed that administration of Actein significantly inhibited glioma cell viability in a dose- and time-dependent manner. Actein also increasingly inhibited the colony formation processes in glioma U87 cells and U251 cells. Administration of Actein also induced mitochondria-related apoptosis by increasing expression of pro-apoptotic factors Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) as well as decreasing …anti-apoptotic Bcl-2 expression in U87 cells and U251 cells. In a xenograft model of glioma, Actein suppressed tumor growth and consistently induced cell apoptosis with the same mechanisms observed in vitro . In all, this study is the first report to address the growth inhibitory effects of Actein on glioma growth and propose that mitochondria-mediated apoptosis pathway may underlie the biological activities of Actein in glioma. Our study suggests that administration of Actein may serve as a potent therapeutic strategy for treatment of glioma. Show more

Keywords: Actein, glioma, growth, mitochondria, apoptosis

DOI: 10.3233/CBM-160095

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 329-338, 2017

Authors: Lin, Yun | Chen, Wei-Ming | Wang, Chen | Chen, Xiao-Yan

Article Type: Research Article

Abstract: BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is an obviously heterogeneous and highly invasive malignancy without definite phenotype. MicroRNAs (miRNAs) are powerful gene regulators and have been reported as biomarkers in many malignancies. OBJECTIVE: To discover potential signaling miRNAs in PTCL-NOS distinguished from reactive lymphoid hyperplasia (RLH) and to explore the molecular characteristics based on the discovery. METHODS: We measured the expression profile of miRNAs in PTCL-NOS and RLH from our patients using a panel PCR array. We used GO-Analysis to evaluate the function of the targets regulated by the detected miRNAs. …Then using pathway enrichment analysis, we defined potential pathways connected with the selected miRNAs. RESULTS: We found 20 miRNAs which were remarkably up/down-regulated in PTCL-NOS. GO-Analysis and pathway analysis indicated 61 GOs and 34 signaling pathways that were significantly increased or decreased regarding tumorigenesis, tumor progression, invasion, metastasis, and drug resistance. CONCLUSIONS: Briefly, our results suggest that 20 miRNAs have the potential to be used as biomarker for identification of patients with PTCL-NOS. Show more

Keywords: Peripheral T-cell lymphoma, microRNA, profiling, tumorigenesis, drug resistance

DOI: 10.3233/CBM-160126

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 339-347, 2017

Authors: Sheibani, Shoaleh | Mahmoudian, Reihaneh Alsadat | Abbaszadegan, Mohammad Reza | Chamani, Jamshidkhan | Memar, Bahram | Gholamin, Mehran

Article Type: Research Article

Abstract: BACKGROUND: Matrix metalloproteinases (MMPs) can degrade essentially the extracellular matrix (ECM) components. MMPs are important regulators of tumor growth; hence the enzymes are considered as important targets for cancer therapy. MMP-13 is specially activated in gastric cancer and promotes the invasiveness of the primary tumors. Helicobacter Pylori (H.pylori ) interacts with gastric epithelial cells and stimulates it to produce MMP-13 in vitro . OBJECTIVE: The relation between MMP-13 gene expression and clinicopathological characteristics of gastric cancer in the presence of H.pylori infection was investigated in fifty patients. METHODS: The …level of MMP-13 gene expression was measured by quantitative Real-time PCR method and was evaluated between two groups of normal and carcinomatous tissues. RESULTS: The results showed 30% elevation of MMP-13 expression in tumor tissues. H.pylori infection did not have a significant effect on the expression of MMP-13 . There was a correlation between gene expression and tumor type (P value = 0.032). In addition, there was a significant correlation between MMP-13 gene expression and tumor stage in intestinal group (P value = 0.023). CONCLUSIONS: Based on the results, it might be concluded that in intestinal group, immune system plays an important role in reducing gene expression. Results also showed over expression (60%) in diffuse group. These findings suggest that using MMP-13 inhibitors in diffuse group might contribute to the control of tumor growth. Show more

Keywords: MMP-13, gastric cancer, Helicobacter Pylori, real-time PCR

DOI: 10.3233/CBM-160127

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 349-356, 2017

Authors: Pan, Yinghua | Liu, Peiji | Chen, Deng | Dou, Linying

Article Type: Research Article

Abstract: OBJECTIVE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers and often shows resistance to multimodal therapeutic approaches. It has been shown that the transcriptional repressor Slug inhibits the chemotherapeutic agent-induced apoptosis of cancer cells. We evaluated whether targeting of Slug could augment doxorubicin (DOX)-induced apoptosis of ATC cells. We also determined changes in PUMA (p53-upregulated modulator of apoptosis) expression levels to identify possible mechanisms of their combined actions. METHODS: SW1736 cells were transfected with Slug siRNA or/and PUMA siRNA and then exposed to DOX (0.1, 1, and 5 μ M) for …selected times. Scrambled siRNA was used as a control. The effects on cell viability were determined via MTT assay. Apoptosis was assessed using TUNEL assays and annexin V staining, and was confirmed by flow cytometry analyses. Slug and PUMA levels were determined using western blotting, RT-PCR and immunofluorescence analyses. We used a subcutaneous implanted tumor model of SW1736 cells in nude mice to assess the effects of Slug silencing in combination with DOX on tumor development. Apoptosis was assessed via TUNEL assay. RESULTS: Targeting of Slug using siRNA inhibits growth of SW1736 cells and sensitizes SW1736 cells to DOX in vitro and vivo. Targeting of Slug combined with DOX led to lower cell viability than treatment with DOX alone in SW1736 cells. TUNEL and flow cytometry analyses showed that targeting of Slug enhanced DOX-induced apoptosis of SW1736 cells. In addition, targeting of Slug increased PUMA expression, and targeting of PUMA restored the chemoresistance of SW1736/Slug siRNA cells to DOX. CONCLUSIONS: Knockdown of Slug enhanced the antitumor activity of DOX in SW1736 cells via induction of PUMA upregulation. Our results suggest that targeting of Slug has good potential for the development of new therapeutic strategies for ATC. Show more

Keywords: Anaplastic thyroid carcinoma, chemotherapy, Slug, PUMA

DOI: 10.3233/CBM-160192

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 357-366, 2017

Authors: Shan, Xiu-Hong | Wang, Peng | Xiong, Fei | Lu, Hao-Yue | Hu, Hui

Article Type: Research Article

Abstract: BACKGROUND: Breast cancer is one of the most common type of female cancer worldwide and represents 14% of cancer-related deaths in women. Early detection is the most important factor for treatment and prognosis of breast cancer. In most countries, the women are currently screened with mammography only. Even though there has been considerable progress in the detection, surgical therapy, hormonal and target therapy of breast cancer, there are about ∼ 3500 000 women who die from breast cancer each year. Therefore, there is an urgent need to explore the new techniques for early detection of breast cancer. Magnetic resonance …imaging (MRI) has the potential to improve breast cancer detection at an early stage because of its higher sensitivity. Glucose transporter (Glut) is a cellular transmembrane receptor that plays key roles in cell glucose metabolism and over-expressed in breast cancer cells. 2-deoxy-D-glucose having a similar structure to D-glucose can specifically interact with Glut. METHODS: In the present study, we constructed a 2-deoxy-D-glucose-functionalized superparamagnetic iron oxide (SPIO) nanoparticles that coated with meso-2,3-dimercaptosuccinic acid (γ-Fe2 O3 @DMSA-DG NPs). The aim of this study is to evaluate the efficacy of new constructed MRI contrast agent (γ-Fe2 O3 @DMSA-DG NPs) in detecting human breast cancers. RESULTS: Our results showed that breast cancer cells MDA-MD-231, MCF7 and ZR-75-1 had a high uptake rate of γ-Fe2 O3 @DMSA-DG NPs than human breast fibroblast cell HUM-CELL-0056. There was a significant difference of T2 relaxation times and signal intensity between breast cancer cells and human breast fibroblast cells labeled with γ-Fe2 O3 @DMSA-DG NPs when MIR. CONCLUSION: Our results indicated that γ-Fe2 O3 @DMSA-DG NPs may be used as a new MRI contrast agent for detection of breast cancer. Show more

Keywords: Glucose transporter, breast cancer, SPIO, MRI

DOI: 10.3233/CBM-160258

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 367-374, 2017

Authors: Shahriari, Shadab | Rezaeifard, Somayeh | Moghimi, Hamid Reza | Khorramizadeh, Mohammad Reza | Faghih, Zahra

Article Type: Research Article

Abstract: BACKGROUND: Toll-like receptor 9 (TLR9) is a DNA receptor of innate immune system which plays a pivotal role in inflammatory response. Recent evidence reveals over-expression and functionality of TLR9 in a wide variety of cancer cells and its contribution to tumor cell proliferation and survival. OBJECTIVE: In this study, we assessed the aberrant cell surface expression of TLR9 in cancer using cell-lines model. METHODS: Three breast cancer cell-lines (MDA-MB-231, MCF7 and SKBR3) and five colorectal adenocarcinoma cell-lines (HT29, HT29/219, SW480, SW48 and SW1116) in addition to one primary foreskin isolated fibroblast cell were …analyzed for cell surface and intracellular expression of TLR9 by flow cytometry method. RESULTS: Maximum surface expression of TLR9 was observed in colorectal cell-line HT29/219 (38.35%), as compared with the bottom line fibroblast normal cells (0.12%). The most intracellular expression was observed in MCF-7 cells (35.63%), whereas MDA-MB-231 expressed the maximum surface/intra cellular expression (277 times). CONCLUSIONS: Based on the results, we hypothesize that aberrant surface expression of TLR9 on tumor cells may promote tumor growth and invasion. It might also highlight a dual contradictory role for CpG-ODNs, as adjutant in cancer therapy. Show more

Keywords: TLR9, colon cancer, breast cancer

DOI: 10.3233/CBM-160260

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 375-380, 2017

Authors: Fantony, Joseph J. | Longo, Thomas A. | Gopalakrishna, Ajay | Owusu, Richmond | Lance, Raymond S. | Foo, Wen-Chi | Inman, Brant A. | Abern, Michael R.

Article Type: Research Article

Abstract: BACKGROUND: Abnormal methylation of urinary TWIST1 and NID2 conferred high sensitivity and specificity for the detection of urothelial carcinoma. OBJECTIVE: We examine the performance of the urine-based TWIST1/NID2 methylation assay with the addition of urine cytology for the detection of urothelial carcinoma. MATERIALS AND METHODS: A prospective multi-institutional study was conducted to assess the performance of a methylation assay for patients with hematuria or under surveillance for non-muscle invasive bladder cancer (NMIBC). All patients underwent cystoscopy, a methylation assay, and cytology. Receiver operator characteristic (ROC) curves were constructed for cytology alone, …the methylation assay alone, and a combined model. Areas under the curve (AUC) were compared using likelihood ratio tests. RESULTS: A total of 172 patients were enrolled (37% for hematuria and 63% NMIBC). The AUC for cytology alone with equivocal cytologies positive was 0.704, and improved to 0.773 with the addition of the DNA methylation assay (p < 0.001). When the equivocal cytologies were considered negative, the AUC improved from 0.558 to 0.697 with the addition of the DNA methylation assay (p = 0.003). CONCLUSIONS: Addition of a TWIST1/NID2-based DNA methylation assay adds diagnostic value to urine cytology and the model is sensitive to the classification of equivocal cytology. Show more

Keywords: Diagnostic test, epigenetic, sensitivity, specificity, urothelial carcinoma, smoking

DOI: 10.3233/CBM-160261

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 381-387, 2017

Authors: Malik, Showkat A. | Khan, Mosin S. | Dar, Majeed | Hussain, Mahboob Ul | Mudassar, Syed

Article Type: Research Article

Abstract: BACKGROUND: Hippo-LATS pathway is involved in regulating multiple phenotypes. TAZ (transcriptional co-activator with PDZ-binding motif) is a prominent proto-oncogene of this developmental pathway. Elevated TAZ expression has been observed in many cancers including Non-Small Cell lung cancer (NSCLC). OBJECTIVE: We elucidated the frequency of protein expression of TAZ gene in NSCLC patients of our population along with its relationship with clinicopathological parameters and determined its prognostic significance concerning survival in patients with resected tumor. METHODS: We looked into the protein expression of TAZ gene in sixty nine (n= 69) cases …of NSCLC tissue and their corresponding normal lung tissue samples by western blotting. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of TAZ protein expressionon survival. RESULTS: Here, we found that TAZ protein expression was elevated in 49.27% (34 of 69) of NSCLC tissues as compared to only 13.04% (09 of 69) in normal lung tissues. TAZ protein expression was significantly associated with smoking, positive lymph node status and vascular invasion (P< 0.05). TAZ protein overexpression increased the hazards ratio by 2.6 (P= 0.005) on univariate analysis. Multivariable analysis confirmed that TAZ protein overexpression along with age and lymph node metastasis increased the hazard of death after adjusting for other clinicopathological factors (P< 0.05). Importantly, TAZ protein overexpression was associated with short overall survival and disease-free survival when compared with normal TAZ expression. CONCLUSION: These results indicate that TAZ is an independent prognostic factor and plays an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC. Show more

Keywords: Lung cancer, survival, protein expression, hazard ratio, TAZ, NSCLC

DOI: 10.3233/CBM-160263

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 389-395, 2017

Authors: Sun, Weiliang | Mo, Xiaoyan | Li, Tianwen | Xie, Yi | Guo, Junming

Article Type: Research Article

Abstract: BACKGROUND: Long non-coding RNAs (lncRNAs) play roles in carcinogenesis; however, the significance of most lncRNAs in gastric cancer is unclear. OBJECTIVE: To explore the diagnostic value of the long noncoding RNA RP11-19P22.6-001 in gastric cancer. METHODS: RP11-19P22.6-001 levels in gastric cancer tissues and paired non-tumor tissues were analyzed by quantitative reverse transcription-polymerase chain reaction. Since RP11-19P22.6-001 acts in cis to regulate nitric oxide synthase 2 (NOS2), we also analyzed NOS2 expression and its correlation with gastric cancer. Finally, to analyze the potential diagnostic values of RP11-19P22.6-001, a receiver operating characteristic (ROC) curve was …constructed. RESULTS: RP11-19P22.6-001 expression was significantly downregulated in 70.91% (78/110) of gastric cancer tissues compared to that of adjacent normal tissues. However, NOS2 was upregulated in 75.45% (83/110) of gastric cancer tissues. RP11-19P22.6-001 expression levels were associated with invasion, lymph node metastasis, and TNM stage. The areas under the ROC curves (AUC) were 0.662 and 0.671 for RP11-19P22.6-001 and NOS2, respectively. More importantly, the combined use of these parameters increased the AUC to 0.704. CONCLUSIONS: RP11-19P22.6-001 and NOS2 may be new biomarkers for the diagnosis and prognosis of gastric cancer. The combined use of lncRNAs and their target genes may be a promising method to increase the diagnostic value of lncRNAs in cancer. Show more

Keywords: Gastric cancer, long non-coding RNA, RP11-19P22.6-001, nitric oxide synthase 2, biomarker

DOI: 10.3233/CBM-160264

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 397-403, 2017

Authors: Zhang, Xu-Hua | Zhang, Yue | Xie, Wen-Peng | Sun, De-Sheng | Zhang, Yong-Kui | Hao, Yan-Ke | Tan, Guo-Qing

Article Type: Research Article

Abstract: BACKGROUND: As one of the endoplasmic reticulum proteins, calreticulin (CRT) plays a significant role in the body, and it has been used by many researchers as a target for anti-tumor therapy. OBJECTIVE: The main purpose of the present study was to study expression of CRT of human osteosarcoma, and analyze the distinctions between normal and tumor tissues, pre- and post-chemotherapy patients, and metastatic and non-metastatic tumors in respect to this expression. METHODS: Immunofluorescent staining was used in order to investigate expression of CRT in diverse tissues. The whole RNA and proteins were extracted …from the crushed tissues and used in the reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis. RESULTS: The present study detected expression of CRT in patients with osteosarcoma and revealed a higher expression level in normal tissues surrounding tumors compared with tumor tissues, in the non-metastasis group compared with the metastasis group, and in the chemotherapy group compared with the non-chemotherapy group. CONCLUSIONS: These results could indicate a brand-new biological marker which may be applied to estimate the features and prognosis of osteosarcoma. Show more

Keywords: Osteosarcoma, Calreticulin, immunofluorescent staining, reverse transcription polymerase chain reaction, western blot analysis

DOI: 10.3233/CBM-160266

Citation: Cancer Biomarkers, vol. 18, no. 4, pp. 405-411, 2017