Special Issue "Models of Experimental Liver Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 31 August 2019

Special Issue Editor

Guest Editor
Prof. Dr. Diego F. Calvisi

Professor of Experimental Tumor Pathology, Institut für Pathologie, Universitätsklinikum, Regensburg, Germany;
Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
Website | E-Mail
Interests: liver cancer; hepatocellular carcinoma; cholangiocarcinoma; hepatoblastoma; mouse models; cancer genetics and epigenetics; signal transduction; cancer metabolism; precision medicine

Special Issue Information

Dear Colleagues,

Primary liver cancer (PLC) ranks among the most frequent and deadly tumors worldwide, with a steadily increasing incidence and few therapeutic options. PLC consists of two main histological subtypes in the adult, namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), and of hepatoblastoma (HBL) in children. Due to the paucity of symptoms and the absence of reliable biomarkers for early detection, PLC is most often detected in advanced stages, when curative therapies are not applicable and loco-regional approaches are of limited patient benefit. To overcome this gloomy scenario, a number of in vitro and in vivo experimental models have been generated and are currently under development. These models have been highly useful to understand the genetic predisposition to liver cancer, the malignant properties of chemicals and environmental factors, the histopathological alterations occurring along liver tumor development and progression, the identification of diagnostic and prognostic markers, and the oncogenic potential of aberrantly activated or inactivated signaling pathways. Recent and future models will be extremely helpful to address pivotal unsolved questions, such as intratumor heterogeneity, functional interplay between PLC cells and the tumor microenvironment, the role of signaling pathways crosstalk, metabolic addiction, and response/resistance to conventional and tailored therapies.

Given the importance of PLC in the field of medicine and research, the journal Cancers is launching this Special Issue. Our aim is to bring together a collection of original research articles and incisive reviews providing fertile ground for insightful discussions and new ideas for the understanding and the treatment of this pernicious disease.

Prof. Dr. Diego F. Calvisi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (2 papers)

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Research

Open AccessArticle Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine
Cancers 2019, 11(4), 519; https://doi.org/10.3390/cancers11040519
Received: 7 March 2019 / Revised: 5 April 2019 / Accepted: 7 April 2019 / Published: 11 April 2019
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Abstract
Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. Late diagnosis and chemotherapy resistance contribute to the scarce outfit and poor survival. Resistance mechanisms are still poorly understood. Here, we established a Gemcitabine (GEM) resistant model, the MT-CHC01R1.5 cell line, obtained [...] Read more.
Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. Late diagnosis and chemotherapy resistance contribute to the scarce outfit and poor survival. Resistance mechanisms are still poorly understood. Here, we established a Gemcitabine (GEM) resistant model, the MT-CHC01R1.5 cell line, obtained by a GEM gradual exposure (up to 1.5 µM) of the sensitive counterpart, MT-CHC01. GEM resistance was irreversible, even at high doses. The in vitro and in vivo growth was slower than MT-CHC01, and no differences were highlighted in terms of migration and invasion. Drug prediction analysis suggested that Paclitaxel and Doxycycline might overcome GEM resistance. Indeed, in vitro MT-CHC01R1.5 growth was reduced by Paclitaxel and Doxycycline. Importantly, Doxycycline pretreatment at very low doses restored GEM sensitivity. To assess molecular mechanisms underlying the acquisition of GEM resistance, a detailed analysis of the transcriptome in MT-CHC01R1.5 cells versus the corresponding parental counterpart was performed. Transcriptomic analysis showed that most up-regulated genes were involved in cell cycle regulation and in the DNA related process, while most down-regulated genes were involved in the response to stimuli, xenobiotic metabolism, and angiogenesis. Furthermore, additional panels of drug resistance and epithelial to mesenchymal transition genes (n = 168) were tested by qRT-PCR and the expression of 20 genes was affected. Next, based on a comparison between qRT-PCR and microarray data, a list of up-regulated genes in MT-CHC01R1.5 was selected and further confirmed in a primary cell culture obtained from an ICC patient resistant to GEM. In conclusion, we characterized a new GEM resistance ICC model that could be exploited either to study alternative mechanisms of resistance or to explore new therapies. Full article
(This article belongs to the Special Issue Models of Experimental Liver Cancer)
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Open AccessArticle Assessment of a High Sensitivity Method for Identification of IDH1 R132x Mutations in Tumors and Plasma of Intrahepatic Cholangiocarcinoma Patients
Cancers 2019, 11(4), 454; https://doi.org/10.3390/cancers11040454
Received: 11 March 2019 / Revised: 26 March 2019 / Accepted: 28 March 2019 / Published: 30 March 2019
PDF Full-text (2295 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Hotspot codon 132 mutations (R132xIDH1m) are frequent in intrahepatic cholangiocarcinoma (ICC), are druggable by anti-IDH1m agents, and could represent a marker of disease progression. Developing an assay to identify R132xIDH1m would provide a useful tool to select [...] Read more.
Hotspot codon 132 mutations (R132xIDH1m) are frequent in intrahepatic cholangiocarcinoma (ICC), are druggable by anti-IDH1m agents, and could represent a marker of disease progression. Developing an assay to identify R132xIDH1m would provide a useful tool to select patients benefitting from targeted treatments. We tested a quantitative real-time allele-specific polymerase chain reaction (qPCR)-based method to detect the main R132xIDH1m in an Italian ICC series (n = 61) of formalin-fixed paraffin-embedded (FFPE) samples, and on circulating-free DNA samples. The outcomes were compared with nested PCR/Sanger sequencing. Reconstitution experiments of plasmids harboring the different R132xIDH1m mixed with wild-type (WT) DNA demonstrated that qPCR is able to detect at least 2% of all mutated allele. High efficiency was also observed on patient-derived mutated DNA mixed with WT DNA (up to 10% and 0.3 ng of mutated template); qPCR detected 16.4% of mutated samples (one R132G, three R132C and six R132L) while nested PCR/Sanger sequencing only 8.2% (four R132L and one R132G). In a single patient with an R132C-mutated tumor, qPCR was also performed on plasma samples collected at four time-points, observing an increase correlating with disease progression. In conclusion, we developed a qPCR assay which could represent a fast, inexpensive and sensitive tool both for detection of R132xIDH1m in ICC samples and monitoring disease progression from liquid biopsy. Full article
(This article belongs to the Special Issue Models of Experimental Liver Cancer)
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