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J. Clin. Med., Volume 4, Issue 12 (December 2015)

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Open AccessFeature PaperReview
Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?
J. Clin. Med. 2015, 4(12), 2028-2041; https://doi.org/10.3390/jcm4121958
Received: 19 November 2015 / Revised: 4 December 2015 / Accepted: 14 December 2015 / Published: 19 December 2015
Cited by 21 | Viewed by 2168 | PDF Full-text (493 KB) | HTML Full-text | XML Full-text
Abstract
In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the [...] Read more.
In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the epithelial cells lining the bile ducts (cholangiocytes) and characterized by an abundant stromal reaction. CCA carries a dismal prognosis, owing to a pronounced invasiveness and scarce therapeutic opportunities. In CCA, several reports indicate that cancer cells acquire a number of EMT biomarkers and functions. These phenotypic changes are likely induced by both autocrine and paracrine signals released in the tumor microenvironment (cytokines, growth factors, morphogens) and intracellular stimuli (microRNAs, oncogenes, tumor suppressor genes) variably associated with specific disease mechanisms, including chronic inflammation and hypoxia. Nevertheless, evidence supporting a complete EMT of neoplastic cholangiocytes into stromal cells is lacking, and the gain of EMT-like changes by CCA cells rather reflects a shift towards an enhanced pro-invasive phenotype, likely induced by the tumor stroma. This concept may help to identify new biomarkers of early metastatic behavior along with potential therapeutic targets. Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition)
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Open AccessArticle
Detection of Exosomal miRNAs in the Plasma of Melanoma Patients
J. Clin. Med. 2015, 4(12), 2012-2027; https://doi.org/10.3390/jcm4121957
Received: 3 August 2015 / Revised: 1 December 2015 / Accepted: 4 December 2015 / Published: 17 December 2015
Cited by 44 | Viewed by 3242 | PDF Full-text (1635 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are a class of 22–25 nucleotide RNAs that control gene expression at the post-transcriptional level. MiRNAs have potential as cancer biomarkers. Melanoma is a highly aggressive form of skin cancer accounting for almost 4% of cancers among men and women, and [...] Read more.
MicroRNAs (miRNAs) are a class of 22–25 nucleotide RNAs that control gene expression at the post-transcriptional level. MiRNAs have potential as cancer biomarkers. Melanoma is a highly aggressive form of skin cancer accounting for almost 4% of cancers among men and women, and ~80% of skin cancer-related deaths in the US. In the present study we analyzed plasma-derived exosomal miRNAs from clinically affected and unaffected familial melanoma patients (CDKN2A/p16 gene carriers) and compared them with affected (nonfamilial melanoma) and unaffected control subjects in order to identify novel risk biomarkers for melanoma. Intact miRNAs can be isolated from the circulation because of their presence in exosomes. A number of differentially regulated miRNAs identified by NanoString human V2 miRNA array were validated by quantitative PCR. Significantly, miR-17, miR-19a, miR-21, miR-126, and miR-149 were expressed at higher levels in patients with metastatic sporadic melanoma as compared with familial melanoma patients or unaffected control subjects. Surprisingly, no substantial differences in miRNA expression were detected between familial melanoma patients (all inclusive) and unaffected control subjects. The miRNAs differentially expressed in the different patient cohorts, especially in patients with metastatic melanoma, may play important roles in tumor progression and metastasis, and may be used as predictive biomarkers to monitor remission as well as relapse following therapeutic intervention. Full article
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Open AccessReview
Pork as a Source of Omega-3 (n-3) Fatty Acids
J. Clin. Med. 2015, 4(12), 1999-2011; https://doi.org/10.3390/jcm4121956
Received: 3 November 2015 / Revised: 8 December 2015 / Accepted: 8 December 2015 / Published: 16 December 2015
Cited by 23 | Viewed by 2661 | PDF Full-text (902 KB) | HTML Full-text | XML Full-text
Abstract
Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs [...] Read more.
Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority. Full article
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease) Printed Edition available
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Open AccessCorrection
Correction: Ripamonti, C.; Trippa, F.; Barone, G.; Maranzano, E. Prevention and Treatment of Bone Metastases in Breast Cancer. J. Clin. Med. 2013, 2, 151–175
J. Clin. Med. 2015, 4(12), 1998; https://doi.org/10.3390/jcm4121955
Received: 30 November 2015 / Revised: 4 December 2015 / Accepted: 4 December 2015 / Published: 10 December 2015
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Abstract
The authors wish to make the following corrections to this paper [1]: The authors’ names: [...] Full article
Open AccessArticle
Relevance of Rabbit VX2 Tumor Model for Studies on Human Hepatocellular Carcinoma: A MicroRNA-Based Study
J. Clin. Med. 2015, 4(12), 1989-1997; https://doi.org/10.3390/jcm4121954
Received: 23 August 2015 / Revised: 13 November 2015 / Accepted: 27 November 2015 / Published: 4 December 2015
Cited by 2 | Viewed by 2115 | PDF Full-text (618 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs are small (~22 nt), noncoding RNA molecules that have critical cellular functions in proliferation, differentiation, angiogenesis and apoptosis. miRNA expression profiling has been used to create signatures of solid tumors and, in many cases, it has been shown to correlate with the [...] Read more.
MicroRNAs are small (~22 nt), noncoding RNA molecules that have critical cellular functions in proliferation, differentiation, angiogenesis and apoptosis. miRNA expression profiling has been used to create signatures of solid tumors and, in many cases, it has been shown to correlate with the severity of the disease. The rabbit VX2 tumor model has been used widely to study a number of human cancers. Our objective in this study is to generate an miRNA signature of the VX2 tumor and to identify miRNAs that are highly expressed in this aggressive tumor. In this study, we performed miRNA profiling of the rabbit VX2 tumor using a microarray that has probes for 1292 unique miRNAs. Their expression in tumor samples was quantified and analyzed. We found that 35 miRNAs were significantly up-regulated in the VX2 tumor. Among these, 13 human miRNAs and eight members of the let-7 family were previously identified in cancers. In addition, we show that the expression of three miRNAs (miR-923, miR-1275, and miR-1308) is novel for the rabbit VX2 tumor, and their expression was not previously shown to be associated with any type of cancer. For the first time, we show the miRNA signature profile for a solid tumor in a rabbit model. miRNAs highly expressed in the VX2 tumor may serve as novel candidates for molecular biomarkers and as potential drug targets. Full article
(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers for Liver Diseases)
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Open AccessReview
MicroRNAs in Nonalcoholic Fatty Liver Disease
J. Clin. Med. 2015, 4(12), 1977-1988; https://doi.org/10.3390/jcm4121953
Received: 19 October 2015 / Revised: 20 November 2015 / Accepted: 27 November 2015 / Published: 4 December 2015
Cited by 22 | Viewed by 5962 | PDF Full-text (509 KB) | HTML Full-text | XML Full-text
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs) play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD. Full article
(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers for Liver Diseases)
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Open AccessReview
Claudin 1 in Breast Cancer: New Insights
J. Clin. Med. 2015, 4(12), 1960-1976; https://doi.org/10.3390/jcm4121952
Received: 1 October 2015 / Revised: 9 November 2015 / Accepted: 14 November 2015 / Published: 27 November 2015
Cited by 14 | Viewed by 3221 | PDF Full-text (785 KB) | HTML Full-text | XML Full-text
Abstract
Claudin 1 is a small transmembrane protein responsible for maintaining the barrier function that exists between epithelial cells. A tight junction protein that regulates the paracellular transport of small ions across adjacent cells, claudin 1 maintains cellular polarity and plays a major role [...] Read more.
Claudin 1 is a small transmembrane protein responsible for maintaining the barrier function that exists between epithelial cells. A tight junction protein that regulates the paracellular transport of small ions across adjacent cells, claudin 1 maintains cellular polarity and plays a major role in cell-cell communication and epithelial cell homeostasis. Long considered to be a putative tumor suppressor in human breast cancer, new studies suggest a role much more complex. While most invasive breast cancers exhibit a down regulation or absence of claudin 1, some aggressive subtypes that exhibit high claudin 1 levels have now been described. Furthermore, a causal role for claudin 1 in breast cancer progression has recently been demonstrated in some breast cancer cell lines. In this review we highlight new insights into the role of claudin 1 in breast cancer, including its involvement in collective migration and epithelial mesenchymal transition (EMT). Full article
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition)
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J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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