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1712 KiB

Open AccessArticle

Increased Exosomal MicroRNA-21 and MicroRNA-146a Levels in the Cervicovaginal Lavage Specimens of Patients with Cervical Cancer

by Jie Liu, Hong Sun, Xiaoli Wang, Qun Yu, Shuhong Li, Xiaoyan Yu and Wenwen Gong

Int. J. Mol. Sci. 2014, 15(1), 758-773; https://doi.org/10.3390/ijms15010758 - 8 Jan 2014

Cited by 129 | Viewed by 9894

Abstract

Well-run screening programs for cervical cancer in the population at risk have been shown to result in a sharp decrease in the incidence and mortality of cervical cancer in a number of large populations. Expression patterns of a recently identified biomarker family, microRNA, [...] Read more.

Well-run screening programs for cervical cancer in the population at risk have been shown to result in a sharp decrease in the incidence and mortality of cervical cancer in a number of large populations. Expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin. Several tumors have been reported to actively release exosomes carrying microRNAs. The present study has determined the association of microRNAs with cervical cancer-derived exosomes. The cervical cancer-derived exosomes were enriched in the cervicovaginal lavages specimens and the abundance of exosomes and exosomal microRNAs was detected by electron microscopy, western blot analysis, RT-qPCR and microRNA target reporter vector. The microRNA-21 and microRNA-146a, which were up-regulated in cervical cancer patients, were associated with the high levels of cervical cancer-derived exosomes. In conclusion, we demonstrated the abundance of exosomes in the cervicovaginal lavage specimens of women with cervical cancer. Furthermore, our results indicated that abnormally high levels of microRNA-21 and microRNA-146a existed in the cervical cancer-derived exosomes and the two microRNAs were functional in 293T cells. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features

by Yuanyang Lai, Zhipei Zhang, Jianzhong Li, Dong Sun, Yong'an Zhou, Tao Jiang, Yong Han, Lijun Huang, Yifang Zhu, Xiaofei Li and Xiaolong Yan

Int. J. Mol. Sci. 2013, 14(12), 24549-24559; https://doi.org/10.3390/ijms141224549 - 17 Dec 2013

Cited by 44 | Viewed by 7862

Abstract

We aimed to reveal the true status of epidermal growth factor receptor (EGFR) mutations in Chinese patients with non-small cell lung cancer (NSCLC) after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed [...] Read more.

We aimed to reveal the true status of epidermal growth factor receptor (EGFR) mutations in Chinese patients with non-small cell lung cancer (NSCLC) after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System (ARMS). Correlations between EGFR mutation hotspots and clinical features were also explored. Of the 697 NSCLC patients, 235 (33.7%) patients had tyrosine kinase inhibitor (TKIs) sensitive EGFR mutations in 41 (14.5%) of the 282 squamous carcinomas, 155 (52.9%) of the 293 adenocarcinomas, 34 (39.5%) of the 86 adenosquamous carcinomas, one (9.1%) of the 11 large-cell carcinomas, 2 (11.1%) of the 18 sarcomatoid carcinomas, and 2 (28.6%) of the 7 mucoepidermoid carcinomas. TKIs sensitive EGFR mutations were more frequently found in female patients (p < 0.001), non-smokers (p = 0.047) and adenocarcinomas (p < 0.001). The rates of exon 19 deletion mutation (19-del), exon 21 L858R point mutation (L858R), exon 21 L861Q point mutation (L861Q), exon 18 G719X point mutations (G719X, including G719C, G719S, G719A) were 43.4%, 48.1%, 1.7% and 6.8%, respectively. Exon 20 T790M point mutation (T790M) was detected in 3 squamous carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins) was detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R are two of the more frequent mutations. EGFR mutation detection should be performed as a routine postoperative examination in Chinese NSCLC patients. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Colorectal Laterally Spreading Tumors by Computed Tomographic Colonography

by Yasuo Kakugawa, Yutaka Saito, Takahisa Matsuda, Takeshi Nakajima, Mototaka Miyake and Gen Iinuma

Int. J. Mol. Sci. 2013, 14(12), 23629-23638; https://doi.org/10.3390/ijms141223629 - 3 Dec 2013

Cited by 8 | Viewed by 8896

Abstract

To date, few reports focused primarily on detecting colorectal laterally spreading tumors (LSTs) have been published. The aim of this study was to determine the visibility of LSTs on computed tomographic colonography (CTC) compared with that on colonoscopy as a standard. We retrospectively [...] Read more.

To date, few reports focused primarily on detecting colorectal laterally spreading tumors (LSTs) have been published. The aim of this study was to determine the visibility of LSTs on computed tomographic colonography (CTC) compared with that on colonoscopy as a standard. We retrospectively reviewed and matched data on endoscopic and CTC reports in 157 patients (161 LSTs) who received a multidetector CT scan using contrast media immediately after total colonoscopy at the National Cancer Center Hospital in Tokyo, Japan, between December 2005 and August 2010. The results of the total colonoscopy were known at the time of the CTC procedure and reading. Of the 161 LSTs detected on colonoscopy, 138 were observed and matched by CTC (86%). Of the 91 granular type LSTs (LST-Gs), 88 (97%) were observed and matched, while of the 70 non-granular type LSTs (LST-NGs), 50 (71%) were observed and matched by CTC (p < 0.0001). CTC enabled observation of 73% (22/30) of 20–29 mm, 83% (35/42) of 30–39 mm, 88% (49/56) of 40–59 mm, and 97% (32/33) of ≥60 mm tumors. The rate of observed LSTs by CTC was 86% (97% of LST-G, 71% of LST-NG) of the LSTs found during total colonoscopy. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Evaluation of Individual and Combined Applications of Serum Biomarkers for Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

by Bin Hu, Xiaohui Tian, Jie Sun and Xiangjun Meng

Int. J. Mol. Sci. 2013, 14(12), 23559-23580; https://doi.org/10.3390/ijms141223559 - 2 Dec 2013

Cited by 76 | Viewed by 10069

Abstract

The clinical value of Serum alpha-fetoprotein (AFP) to detect early hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP) [...] Read more.

The clinical value of Serum alpha-fetoprotein (AFP) to detect early hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP) and Golgi protein-73 (GP73) have been identified as useful HCC markers. In this investigation, we review the current knowledge about these HCC-related biomarkers, and sum up the results of our meta-analysis on studies that have addressed the utility of these biomarkers in early detection and prognostic prediction of HCC. A systematic search in PubMed, Web of Science, and the Cochrane Library was performed for articles published in English from 1999 to 2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and specificity of tests were extracted from 40 articles that met the inclusion criteria, and the summary receiver operating characteristic curve (sROC) was obtained. A meta-analysis was carried out in which the area under the curve (AUC) for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73) was used to compare the diagnostic accuracy of different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932 respectively. A combination of AFP + GP73 is superior to AFP in detecting HCC and differentiating HCC patients from non-HCC patients, and may prove to be a useful marker in the diagnosis and screening of HCC. In addition, the AUC of GP73, AFP + DCP and AFP + GP73 are better than that of AFP. The clinical value of GP73, AFP + DCP, or AFP + GP73 as serological markers for HCC diagnosis needs to be addressed further in future studies. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

by Zbynek Heger, Natalia Cernei, Jiri Kudr, Jaromir Gumulec, Iva Blazkova, Ondrej Zitka, Tomas Eckschlager, Marie Stiborova, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2013, 14(11), 21629-21646; https://doi.org/10.3390/ijms141121629 - 31 Oct 2013

Cited by 27 | Viewed by 9886

Abstract

Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a [...] Read more.

Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05). This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

BTG1 Expression Correlates with the Pathogenesis and Progression of Ovarian Carcinomas

by Yang Zhao, Wen-Feng Gou, Shuo Chen, Yasuo Takano, Yin-Ling Xiu and Hua-Chuan Zheng

Int. J. Mol. Sci. 2013, 14(10), 19670-19680; https://doi.org/10.3390/ijms141019670 - 27 Sep 2013

Cited by 27 | Viewed by 6693

Abstract

BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and progression. A BTG1-expressing plasmid was transfected [...] Read more.

BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and progression. A BTG1-expressing plasmid was transfected into ovarian carcinoma cells and their phenotypes and related proteins were examined. BTG1 mRNA expression was detected in ovarian normal tissue (n = 17), ovarian benign tumors (n = 12), and ovarian carcinoma (n = 64) using real-time RT-PCR. Ectopic BTG1 expression resulted in lower growth rate, high cisplatin sensitivity, G₁ arrest, apoptosis, and decreased migration and invasion. Phosphoinositide 3-kinase, protein kinase B, Bcl-xL, survivin, vascular endothelial growth factor, and matrix metalloproteinase-2 mRNA and protein expression was reduced in transfectants as compared to control cells. There was higher expression of BTG1 mRNA in normal tissue than in carcinoma tissue (p = 0.001) and in benign tumors than in carcinoma tissue (p = 0.027). BTG1 mRNA expression in International Federation of Gynecology and Obstetrics (FIGO) stage I/II ovarian carcinomas was higher than that in FIGO stage III/IV ovarian carcinomas (p = 0.038). Altered BTG1 expression might play a role in the pathogenesis and progression of ovarian carcinoma by modulating proliferation, migration, invasion, the cell cycle, and apoptosis. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Exploring the Glycosylation of Serum CA125

by Radka Saldova, Weston B. Struwe, Kieran Wynne, Giuliano Elia, Michael J. Duffy and Pauline M. Rudd

Int. J. Mol. Sci. 2013, 14(8), 15636-15654; https://doi.org/10.3390/ijms140815636 - 26 Jul 2013

Cited by 70 | Viewed by 10671

Abstract

Ovarian cancer is the most lethal gynaecologic cancer affecting women. The most widely used biomarker for ovarian cancer, CA125, lacks sensitivity and specificity. Here, we explored differences in glycosylation of CA125 between serum from patients with ovarian cancer and healthy controls. We found [...] Read more.

Ovarian cancer is the most lethal gynaecologic cancer affecting women. The most widely used biomarker for ovarian cancer, CA125, lacks sensitivity and specificity. Here, we explored differences in glycosylation of CA125 between serum from patients with ovarian cancer and healthy controls. We found differences between CA125 N-glycans from patient sera compared to controls. These include increases in core-fucosylated bi-antennary monosialylated glycans, as well as decreases in mostly bisecting bi-antennary and non-fucosylated glycans in patients compared to controls. Measurement of the glycosylated state of CA125 may therefore provide a more specific biomarker for patients with ovarian cancer. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Graphical abstract

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Open AccessArticle

miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases

by Sumiyo Morita, Takuro Horii, Mika Kimura, Takahiro Ochiya, Shoji Tajima and Izuho Hatada

Int. J. Mol. Sci. 2013, 14(7), 14647-14658; https://doi.org/10.3390/ijms140714647 - 12 Jul 2013

Cited by 117 | Viewed by 11224

Abstract

Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress [...] Read more.

Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposing roles in control of DNA methylation status. Members of the miR-29 family directly inhibited DNA methyltransferases and two major factors involved in DNA demethylation, namely tet methylcytosine dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29 upregulated the global DNA methylation level in some cancer cells and downregulated DNA methylation in other cancer cells, suggesting that miR-29 suppresses tumorigenesis by protecting against changes in the existing DNA methylation status rather than by preventing de novo methylation of DNA. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

The Tumor Suppressor Roles of miR-433 and miR-127 in Gastric Cancer

by Li-Hua Guo, Hui Li, Fang Wang, Jia Yu and Jin-Sheng He

Int. J. Mol. Sci. 2013, 14(7), 14171-14184; https://doi.org/10.3390/ijms140714171 - 8 Jul 2013

Cited by 105 | Viewed by 8490

Abstract

The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, the methylation epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is emerging as a common hallmark of [...] Read more.

The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, the methylation epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is emerging as a common hallmark of different tumors. Here we showed that miR-433 and miR-127 were significantly down-regulated in gastric cancer (GC) tissues compared with the adjacent normal regions in 86 paired samples. Moreover, the lower level of miR-433 and miR-127 was associated with pM or pTNM stage in clinical gastric cancer patients. The restored expression of miR-433 and miR-127 in GC cells upon 5-Aza-CdR and TSA treatment suggested the loss of miR-433 and miR-127 was at least partly regulated by epigenetic modification in GC. Furthermore, the ectopic expression of miR-433 and miR-127 in gastric cancer cell lines HGC-27 inhibits cell proliferation, cell cycle progression, cell migration and invasion by directly interacting with the mRNA encoding oncogenic factors KRAS and MAPK4 respectively. Taken together, our results showed that miR-433 and miR-127 might act as tumor suppressors in GC, and it may provide novel diagnostic and therapeutic options for human GC clinical operation in the near future. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Serum Metallothioneins in Childhood Tumours — A Potential Prognostic Marker

by Jarmila Kruseova, David Hynek, Vojtech Adam, Rene Kizek, Richard Prusa, Jan Hrabeta and Tomas Eckschlager

Int. J. Mol. Sci. 2013, 14(6), 12170-12185; https://doi.org/10.3390/ijms140612170 - 6 Jun 2013

Cited by 6 | Viewed by 6788

Abstract

Metallothioneins (MT) are low molecular weight, cysteine-rich proteins maintaining metal ions homeostasis. They play a role in carcinogenesis and may also cause chemoresistance. The aim of the study was to explore the importance of MT serum levels in children suffering from malignant tumours. [...] Read more.

Metallothioneins (MT) are low molecular weight, cysteine-rich proteins maintaining metal ions homeostasis. They play a role in carcinogenesis and may also cause chemoresistance. The aim of the study was to explore the importance of MT serum levels in children suffering from malignant tumours. This prospective study involves examination of 865 samples from 172 patients with malignant tumours treated from 2008 to 2011 at University Hospital Motol. MT serum levels were determined using differential pulse voltammetry–Brdicka reaction. Mean MT level was 2.7 ± 0.5 μM. There was no statistically significant difference between MT levels in different tumours. We also did not find any correlation between MT levels and response to therapy or clinical stages. However, we found a positive correlation between MT levels and age (p = 0.009) and a negative correlation with absolute lymphocyte number (p = 0.001). The fact that patients who had early disease recurrence had lower MT levels during the treatment (complete remission 2.67 vs. recurring 2.34, p = 0.001) seems to be important for clinical practice. Accordingly we believe that there is benefit in further studies of serum MT levels in tumours. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Prognostic Value of Tumor Markers, NSE, CA125 and SCC, in Operable NSCLC Patients

by Dangfan Yu, Kaiqi Du, Taifeng Liu and Guojun Chen

Int. J. Mol. Sci. 2013, 14(6), 11145-11156; https://doi.org/10.3390/ijms140611145 - 27 May 2013

Cited by 61 | Viewed by 9776

Abstract

The aim of this study was to investigate the prognostic value of tumor markers in operable non-small cell lung cancer (NSCLC) patients. A total of 481 NSCLC patients were enrolled in the present study. High levels of neuron-specific enolase (NSE), carbohydrate antigen 125 [...] Read more.

The aim of this study was to investigate the prognostic value of tumor markers in operable non-small cell lung cancer (NSCLC) patients. A total of 481 NSCLC patients were enrolled in the present study. High levels of neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) were detected in 306 (63.6%), 89 (18.5%) and 125 (26.0%) patients, respectively. Seventy-eight of 481 patients died of disease progression, and the median disease-free survival (DFS) and overall survival (OS) were 16.0 and 21.0 months, respectively. The three-year DFS rate was 56.7%, and the OS rate was 75.3%. For serum NSE, the three-year cumulative DFS rate for the normal and elevated group was 67.7% and 51.8% (p = 0.007). The OS in patients with high and normal levels of NSE was 34.0 months and 48.0 months, respectively. The median DFS was 46.0 months versus 32.0 months (p = 0.001), and the OS was 48.0 months versus 44.0 months (p = 0.001) in patients with normal and high levels of CA125. For patients with squamous cell carcinoma, the overall survival was significantly shorter in patients with elevated levels of SCC (p = 0.041). In the multivariate analysis high levels of NSE, CA125 and clinical stage were signiﬁcantly correlated with worse prognosis (p < 0.05). Patients with all three tumor markers elevated presented the worst prognosis (p < 0.05). In our analysis, high levels of preoperative serum NSE and CA125 are correlated with worse survival in operable NSCLC patients. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Peripheral Blood miR-328 Expression as a Potential Biomarker for the Early Diagnosis of NSCLC

by Paola Ulivi, Giovanni Foschi, Marta Mengozzi, Emanuela Scarpi, Rosella Silvestrini, Dino Amadori and Wainer Zoli

Int. J. Mol. Sci. 2013, 14(5), 10332-10342; https://doi.org/10.3390/ijms140510332 - 16 May 2013

Cited by 70 | Viewed by 8331

Abstract

Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral [...] Read more.

Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral blood, thus representing potential diagnostic biomarkers. We evaluated 100 individuals comprising 86 patients with predominantly early-stage non-small cell lung cancer (NSCLC) and 24 healthy donors. RNA was extracted from peripheral blood samples and the expression of a panel of miRNAs was analyzed by Real-Time PCR method. Expression levels of miR-328, miR-18a, miR-339 and miR-140 were significantly higher in NSCLC patients than in healthy donors (p < 0.05). In particular, miR-328 showed good diagnostic accuracy in discriminating between patients with early NSCLC and healthy donors (AUC ROC 0.82, 95% CI 0.72–0.92), with 70% sensitivity and 83% specificity at the best relative expression cut-off of 300. Moreover, miR-339 was a good discriminant between healthy donors and late-stage NSCLC patients (AUC ROC 0.79, 95% CI 0.68–0.91). In conclusion, miR-328 represents a potential diagnostic biomarker of NSCLC, especially for the identification of early-stage tumors. Its role in discriminating between benign and malignant nodules detected by spiral CT warrants further investigation. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Identification and Validation of a New Set of Five Genes for Prediction of Risk in Early Breast Cancer

by Giorgio Mustacchi, Maria Pia Sormani, Paolo Bruzzi, Alessandra Gennari, Fabrizio Zanconati, Daniela Bonifacio, Adriana Monzoni and Luca Morandi

Int. J. Mol. Sci. 2013, 14(5), 9686-9702; https://doi.org/10.3390/ijms14059686 - 6 May 2013

Cited by 17 | Viewed by 7970

Abstract

Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer [...] Read more.

Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer analyzing several publicly available array gene expression data using R/Bioconductor package. Using RTqPCR we evaluate 261 consecutive invasive breast cancer cases not selected for age, adjuvant treatment, nodal and estrogen receptor status from paraffin embedded sections. The biological samples dataset was split into a training (137 cases) and a validation set (124 cases). The gene signature was developed on the training set and a multivariate stepwise Cox analysis selected five genes independently associated with DFS: FGF18 (HR = 1.13, p = 0.05), BCL2 (HR = 0.57, p = 0.001), PRC1 (HR = 1.51, p = 0.001), MMP9 (HR = 1.11, p = 0.08), SERF1a (HR = 0.83, p = 0.007). These five genes were combined into a linear score (signature) weighted according to the coefficients of the Cox model, as: 0.125FGF18 − 0.560BCL2 + 0.409PRC1 + 0.104MMP9 − 0.188SERF1A (HR = 2.7, 95% CI = 1.9–4.0, p < 0.001). The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, intermediate or high risk of disease relapse as defined on the training set (p < 0.001). Our signature, after a further clinical validation, could be proposed as prognostic signature for disease free survival in breast cancer patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Identification of Plasma Metabolomic Profiling for Diagnosis of Esophageal Squamous-Cell Carcinoma Using an UPLC/TOF/MS Platform

by Ran Liu, Yuan Peng, Xiaobo Li, Yi Wang, Enchun Pan, Wei Guo, Yuepu Pu and Lihong Yin

Int. J. Mol. Sci. 2013, 14(5), 8899-8911; https://doi.org/10.3390/ijms14058899 - 24 Apr 2013

Cited by 50 | Viewed by 7762

Abstract

Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics [...] Read more.

Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells

by Weiwei Shang, Xueqin Chen, Ling Nie, Miao Xu, Ni Chen, Hao Zeng and Qiao Zhou

Int. J. Mol. Sci. 2013, 14(4), 8422-8436; https://doi.org/10.3390/ijms14048422 - 17 Apr 2013

Cited by 27 | Viewed by 7553

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally repress expression of target genes via imperfect base-pairing with the 3'-untranslated region (3'-UTR). The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays important roles in physiology and pathology. Constitutive over-expression of HIF-1α is observed [...] Read more.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally repress expression of target genes via imperfect base-pairing with the 3'-untranslated region (3'-UTR). The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays important roles in physiology and pathology. Constitutive over-expression of HIF-1α is observed in many types of cancers including prostate carcinoma, but the mechanisms underlying this event remain largely unknown. Here we investigated the expression of miR199b and HIF-1α in normal prostate tissue, prostate cancer tissues and prostate carcinoma (PCa) cell lines LNCaP, PC-3 and DU145.We found that miR-199b expression level was decreased in prostate cancer while HIF-1α was significantly over-expressed. Furthermore, we postulated the posttranscriptional regulation of HIF-1α by miR199b through bioinformatics analysis, and herein we experimentally demonstrated that miR199b negatively regulated HIF-1α by targeting its 3'-untranslated region. Artificial over-expression of miR199b by using adenoviral vectors in prostate cancer PC-3 and DU145 cells significantly down-regulated HIF-1α, together with reduced cell growth and increased cell death. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessShort Note

Cholesterol Dependent Uptake and Interaction of Doxorubicin in MCF-7 Breast Cancer Cells

by Petra Weber, Michael Wagner and Herbert Schneckenburger

Int. J. Mol. Sci. 2013, 14(4), 8358-8366; https://doi.org/10.3390/ijms14048358 - 16 Apr 2013

Cited by 29 | Viewed by 7572

Abstract

Methods of fluorescence spectroscopy and microscopy—including intensity and lifetime (FLIM) images—are used to examine uptake, intracellular location and interaction of the chemotherapeutic drug doxorubicin in MCF-7 human breast cancer cells as a function of cholesterol content. By comparing cells with natural and decreased [...] Read more.

Methods of fluorescence spectroscopy and microscopy—including intensity and lifetime (FLIM) images—are used to examine uptake, intracellular location and interaction of the chemotherapeutic drug doxorubicin in MCF-7 human breast cancer cells as a function of cholesterol content. By comparing cells with natural and decreased cholesterol levels after 2 h or 24 h incubation with doxorubicin, we observed that higher fluorescence intensities and possibly shortened fluorescence lifetimes—reflecting increased uptake of the drug and more pronounced drug response—are concomitant with higher membrane fluidity. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Specific siRNA Targeting Receptor for Advanced Glycation End Products (RAGE) Decreases Proliferation in Human Breast Cancer Cell Lines

by AL-Madhagi Radia, AL-Madhagi Yaser, Xiaoqian Ma, Juan Zhang, Cejun Yang, Qiong Dong, Pengfei Rong, Bin Ye, Sheng Liu and Wei Wang

Int. J. Mol. Sci. 2013, 14(4), 7959-7978; https://doi.org/10.3390/ijms14047959 - 11 Apr 2013

Cited by 47 | Viewed by 9652

Abstract

Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to [...] Read more.

Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05). Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Epigenetic Silencing of DKK3 in Medulloblastoma

by Francesca Valdora, Barbara Banelli, Sara Stigliani, Stefan M. Pfister, Stefano Moretti, Marcel Kool, Marc Remke, Alfa H.C. Bai, Claudio Brigati, Thomas Hielscher, Massimo Romani, Tiziana Servidei, Massimo Zollo, Giuseppe Cinalli, André Oberthuer, Gian Paolo Tonini and Simona Coco

Int. J. Mol. Sci. 2013, 14(4), 7492-7505; https://doi.org/10.3390/ijms14047492 - 8 Apr 2013

Cited by 18 | Viewed by 8450

Abstract

Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK) 1–4 family genes, inhibitors of the Wnt [...] Read more.

Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum consisting of four distinct subgroups: WNT, SHH, Group 3 and Group 4, which exhibit different molecular phenotypes. We studied the expression of Dickkopf (DKK) 1–4 family genes, inhibitors of the Wnt signaling cascade, in MB by screening 355 expression profiles derived from four independent datasets. Upregulation of DKK1, DKK2 and DKK4 mRNA was observed in the WNT subgroup, whereas DKK3 was downregulated in 80% MBs across subgroups with respect to the normal cerebellum (p < 0.001). Since copy number aberrations targeting the DKK3 locus (11p15.3) are rare events, we hypothesized that epigenetic factors could play a role in DKK3 regulation. Accordingly, we studied 77 miRNAs predicting to repress DKK3; however, no significant inverse correlation between miRNA/mRNA expression was observed. Moreover, the low methylation levels in the DKK3 promoters (median: 3%, 5% and 5% for promoter 1, 2 and 3, respectively) excluded the downregulation of gene expression by methylation. On the other hand, the treatment of MB cells with Trichostatin A (TSA), a potent inhibitor of histone deacetylases (HDAC), was able to restore both DKK3 mRNA and protein. In conclusion, DKK3 downregulation across all MB subgroups may be due to epigenetic mechanisms, in particular, through chromatin condensation. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

by Olaf J. C. Hellwinkel, Christina Sellier, Yu-Mi Jessica Sylvester, Jan C. Brase, Hendrik Isbarn, Andreas Erbersdobler, Thomas Steuber, Holger Sültmann, Thorsten Schlomm and Christina Wagner

Int. J. Mol. Sci. 2013, 14(3), 5239-5249; https://doi.org/10.3390/ijms14035239 - 4 Mar 2013

Cited by 17 | Viewed by 6849

Abstract

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or [...] Read more.

We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia

by Yan-Fang Tao, Li Pang, Xiao-Juan Du, Li-Chao Sun, Shao-Yan Hu, Jun Lu, Lan Cao, Wen-Li Zhao, Xing Feng, Jian Wang, Dong Wu, Na Wang, Jian Ni and Jian Pan

Int. J. Mol. Sci. 2013, 14(2), 3376-3394; https://doi.org/10.3390/ijms14023376 - 6 Feb 2013

Cited by 21 | Viewed by 8285

Abstract

Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used [...] Read more.

Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls. The expression profile of histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls. Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300. Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL. Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35). Ingenuity Pathway Analysis also indicated that curcumin and miR-34 are upstream regulators of histone-modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR-34 in leukemia. This study provides new clues into the molecular mechanisms of pediatric ALL. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessArticle

Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma

by Yee-Jee Jan, Bor-Sheng Ko, Tzu-An Liu, Yao-Ming Wu, Shu-Man Liang, Shyh-Chang Chen, John Wang and Jun-Yang Liou

Int. J. Mol. Sci. 2013, 14(1), 1684-1697; https://doi.org/10.3390/ijms14011684 - 15 Jan 2013

Cited by 24 | Viewed by 7492

Abstract

Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, [...] Read more.

Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent risk factor of extrahepatic metastasis. Increased Par-3 expression in primary tumors was associated with poor five-year overall survival rates and was an independent prognostic factor on Cox regression analysis. In conclusion, we show for the first time that increased Par-3 expression is associated with distant metastasis and poor survival rates in patients with HCC. Par-3 may be a novel prognostic biomarker and therapeutic target for HCC. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Inhibitor of Apoptosis Protein-Like Protein-2 as a Novel Serological Biomarker for Breast Cancer

by Mingjun Xiang, Wei Zhou, Dandan Gao, Xiansong Fang and Qian Liu

Int. J. Mol. Sci. 2012, 13(12), 16737-16750; https://doi.org/10.3390/ijms131216737 - 7 Dec 2012

Cited by 15 | Viewed by 6948

Abstract

Inhibitor of apoptosis protein-like protein-2 (ILP-2) has only been detected in the testis and in lymphoblastoid cells. Although previous studies have not reported the presence of ILP-2 in breast cancer tissues, this study indicates the presence of ILP-2 in breast cancer serum samples. [...] Read more.

Inhibitor of apoptosis protein-like protein-2 (ILP-2) has only been detected in the testis and in lymphoblastoid cells. Although previous studies have not reported the presence of ILP-2 in breast cancer tissues, this study indicates the presence of ILP-2 in breast cancer serum samples. To validate whether ILP-2 is a novel serological biomarker for breast cancer, we conducted two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis on 400 breast cancer serum samples and 40 non-cancer serum samples (i.e., healthy controls). We then performed a Western blot analysis of 10 breast cancer serum samples and 10 non-cancer serum samples. Finally, we analyzed 35 serum samples from healthy controls or subjects with breast cancer, other types of cancer, galactophore hyperplasia or breast cancer post-surgery by using 2DE and enzyme-linked immunosorbent assay. Our results indicate that ILP-2 is a novel breast cancer biomarker in the peripheral blood. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Clinicopathological Signiﬁcance of NMIIA Overexpression in Human Gastric Cancer

by Dongning Liu, Lei Zhang, Zhiyong Shen, Fei Tan, Yanfeng Hu, Jiang Yu and Guoxin Li

Int. J. Mol. Sci. 2012, 13(11), 15291-15304; https://doi.org/10.3390/ijms131115291 - 19 Nov 2012

Cited by 33 | Viewed by 8190

Abstract

Altered expressions of nonmuscle myosin IIA (NMIIA) have been observed in certain types of cancers, but the impact of the alterations in gastric cancer (GC) remains unclear. The purpose of this study was to evaluate the expression of NMIIA at the mRNA and [...] Read more.

Altered expressions of nonmuscle myosin IIA (NMIIA) have been observed in certain types of cancers, but the impact of the alterations in gastric cancer (GC) remains unclear. The purpose of this study was to evaluate the expression of NMIIA at the mRNA and protein level in patients with GC and to assess its clinical significance. We investigated the expression of NMIIA in fresh, paired GC tissues by reverse transcriptase polymerase chain reaction (RT-PCR; n = 14) and Western blot analysis (n = 36). Simultaneously, we performed immunohistochemistry (IHC) on paraffin embedded specimens, including 96 GC specimens, 30 matched normal specimens and 30 paired metastatic lymph node samples. NMIIA is overexpressed in GC compared with the adjacent normal gastric epithelium (p < 0.001) and high-level NMIIA expression is significantly correlated with the depth of wall invasion, lymph node metastasis, distant metastasis and Tumor Node Metastasis (TNM) stage. Furthermore, elevated NMIIA expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.021). These findings indicate that overexpression of NMIIA may contribute to the progression and poor prognosis of GC. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Open AccessReview

The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients

by Yahya I. Elshimali, Husseina Khaddour, Marianna Sarkissyan, Yanyuan Wu and Jaydutt V. Vadgama

Int. J. Mol. Sci. 2013, 14(9), 18925-18958; https://doi.org/10.3390/ijms140918925 - 13 Sep 2013

Cited by 200 | Viewed by 16848

Abstract

Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms. Detecting circulating DNA in cancer patients may help develop a DNA profile for early stage diagnosis in malignancies. The technical issues of [...] Read more.

Qualitative and quantitative testing of circulating cell free DNA (CCFDNA) can be applied for the management of malignant and benign neoplasms. Detecting circulating DNA in cancer patients may help develop a DNA profile for early stage diagnosis in malignancies. The technical issues of obtaining, using, and analyzing CCFDNA from blood will be discussed. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Early Lung Cancer Diagnosis by Biosensors

by Yuqian Zhang, Dongliang Yang, Lixing Weng and Lianhui Wang

Int. J. Mol. Sci. 2013, 14(8), 15479-15509; https://doi.org/10.3390/ijms140815479 - 25 Jul 2013

Cited by 50 | Viewed by 9928

Abstract

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as [...] Read more.

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. Full article

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DNA Methylation and Cancer Diagnosis

by Yannick Delpu, Pierre Cordelier, William C. Cho and Jérôme Torrisani

Int. J. Mol. Sci. 2013, 14(7), 15029-15058; https://doi.org/10.3390/ijms140715029 - 18 Jul 2013

Cited by 135 | Viewed by 19294

Abstract

DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the [...] Read more.

DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Clinical Advances in Molecular Biomarkers for Cancer Diagnosis and Therapy

by Seema Sethi, Shadan Ali, Philip A. Philip and Fazlul H. Sarkar

Int. J. Mol. Sci. 2013, 14(7), 14771-14784; https://doi.org/10.3390/ijms140714771 - 16 Jul 2013

Cited by 76 | Viewed by 14456

Abstract

Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded [...] Read more.

Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer. Moreover, deregulating their activity offers novel cancer therapeutic approaches. The availability of high throughput techniques for the identification of altered cellular molecules allowed their use in cancer diagnosis. Their application to a variety of body specimens from blood to tissues has been helpful for appreciating their use in the clinical context. The development of innovative antibodies for immunohistochemical detection of proteins also assists in diagnosis and risk stratification. Overall, the novel cancer diagnostic tools have extended their application as prognostic risk factors and can be used as targets for personalized medicine. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Candidate Biomarkers for Genetic and Clinicopathological Diagnosis of Endometrial Cancer

by Kouji Banno, Yuya Nogami, Iori Kisu, Megumi Yanokura, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Nobuyuki Susumu and Daisuke Aoki

Int. J. Mol. Sci. 2013, 14(6), 12123-12137; https://doi.org/10.3390/ijms140612123 - 6 Jun 2013

Cited by 21 | Viewed by 9978

Abstract

The recent increase in the frequency of endometrial cancer has emphasized the need for accurate diagnosis and improved treatment. The current diagnosis is still based on conventional pathological indicators, such as clinical stage, tumor differentiation, invasion depth and vascular invasion. However, the genetic [...] Read more.

The recent increase in the frequency of endometrial cancer has emphasized the need for accurate diagnosis and improved treatment. The current diagnosis is still based on conventional pathological indicators, such as clinical stage, tumor differentiation, invasion depth and vascular invasion. However, the genetic mechanisms underlying endometrial cancer have gradually been determined, due to developments in molecular biology, leading to the possibility of new methods of diagnosis and treatment planning. New candidate biomarkers for endometrial cancer include those for molecular epigenetic mutations, such as microRNAs. These biomarkers may permit earlier detection of endometrial cancer and prediction of outcomes and are likely to contribute to future personalized therapy for endometrial cancer. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Methylated DNA and microRNA in Body Fluids as Biomarkers for Cancer Detection

by Yanning Ma, Xian Wang and Hongchuan Jin

Int. J. Mol. Sci. 2013, 14(5), 10307-10331; https://doi.org/10.3390/ijms140510307 - 16 May 2013

Cited by 35 | Viewed by 7498

Abstract

Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification [...] Read more.

Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification of circulating cell-free nuclear acids, increasing evidence demonstrated great potential of cell-free epigenetic biomarkers in the blood or other body fluids for cancer detection. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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Biomarkers for Anti-Angiogenic Therapy in Cancer

by Markus Wehland, Johann Bauer, Nils E. Magnusson, Manfred Infanger and Daniela Grimm

Int. J. Mol. Sci. 2013, 14(5), 9338-9364; https://doi.org/10.3390/ijms14059338 - 29 Apr 2013

Cited by 61 | Viewed by 10806

Abstract

Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs), together [...] Read more.

Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs), together with their related VEGF-receptors, have an exceptional position. Therefore, the blockade of VEGF signaling in order to inhibit angiogenesis was deemed an attractive approach for cancer therapy and drugs interfering with the VEGF-ligands, the VEGF receptors, and the intracellular VEGF-mediated signal transduction were developed. Although promising in pre-clinical trials, VEGF-inhibition proved to be problematic in the clinical context. One major drawback was the generally high variability in patient response to anti-angiogenic drugs and the rapid development of therapy resistance, so that, in total, only moderate effects on progression-free and overall survival were observed. Biomarkers predicting the response to VEGF-inhibition might attenuate this problem and help to further individualize drug and dosage determination. Although up to now no definitive biomarker has been identified for this purpose, several candidates are currently under investigation. This review aims to give an overview of the recent developments in this field, focusing on the most prevalent tumor species. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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The Role of Sox Genes in Lung Morphogenesis and Cancer

by Yongzhao Zhu, Yong Li, Jun Wei Jun Wei and Xiaoming Liu

Int. J. Mol. Sci. 2012, 13(12), 15767-15783; https://doi.org/10.3390/ijms131215767 - 26 Nov 2012

Cited by 45 | Viewed by 9664

Abstract

The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer [...] Read more.

The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry) box-containing) family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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