scholarly journals Epithelial–Mesenchymal Transition in Liver Fluke-Induced Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 791
Author(s):  
Kanlayanee Sawanyawisuth ◽  
Goro Sashida ◽  
Guojun Sheng

Cholangiocarcinoma (CCA) is the second most common type of hepatic cancer. In east and southeast Asia, intrahepatic CCA is caused predominantly by infection of Opisthorchis viverrini and Clonorchis sinensis, two species of parasitic liver flukes. In this review, we present molecular evidence that liver fluke-associated CCAs have enhanced features of epithelial–mesenchymal transition (EMT) in bile duct epithelial cells (cholangiocytes) and that some of those features are associated with mis-regulation at the epigenetic level. We hypothesize that both direct and indirect mechanisms underlie parasitic infection-induced EMT in CCA.

2020 ◽  
Vol 17 (3) ◽  
pp. 441-447
Author(s):  
Le Thanh Hoa ◽  
Nguyen Thi Bich Nga ◽  
Doan Thi Thanh Huong ◽  
Le Thi Kim Xuyen ◽  
Nguyen Thi Khue

Opisthorchiasis is a zoonotic parasitic infection caused by small liver fluke species, Opisthorchis viverrini,O. felineus and Clonorchis sinensis, in the family Opisthorchiidae. Vietnam has both species, of which C.sinensis is distributed in the northern and O. viverrini in the central provinces. In addition to the mitochondrialgenomes, the ribosomal DNA sequences (rDNA) of these species are highly needed to obtain for providingmolecular markers in species identification, classification, phylogeny and evolutionary studies. In this study,the near/complete nucleotide sequences of ribosomal transcription units (rTU) from O. viverrini (Vietnamesesample), O. felineus (Russian sample) and C. sinensis (Vietnamese sample) were analyzed. All rTUs for threespecies were determined, which is 7,839 bp for O. viverrini, 6,948 bp for O. felineus and 7,296 bp for C.sinensis containing structures of 18S, ITS1, 5,8S, ITS2 and 28S. The IGS region was not obtained for all threespecies. In all three species, sequence analysis revealed 2 tandem repetitive elements of 47-48 bp/each in ITS1but not in ITS2. The nucleotide sequences of 18S, ITS1, ITS2 and 28S are valuable ribosomal markers that thisstudy provides for diagnosis, identification, taxonomic classification and population genetics. In conclusion,the rTU sequences for the three species of the family Opisthorchiidae have been identified and providesmolecular markers for the use of phylogenetic analysis for species/family classification in the superfamilyOpisthorchioidea and the class Trematoda.


2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110148
Author(s):  
Xue Qiao ◽  
Xing Niu ◽  
Jiayi Liu ◽  
Lijie Chen ◽  
Yan Guo ◽  
...  

Ameloblastoma is a common odontogenic epithelial tumor that exhibits various biological behaviors, ranging from simple cystic expansion to aggressive solid masses characterized by local invasiveness, a high risk of recurrence, and even malignant transformation. We report on two cases of unusually large solid ameloblastomas. We detected epithelial–mesenchymal transition-related gene expression and HRAS gene single nucleotide polymorphisms, providing possible molecular evidence of mesenchymal morphological changes in ameloblastoma. The detailed analysis of the pathogenesis of these two cases of ameloblastoma may deepen our understanding of this rare disease and offer promising targets for future targeted therapy.


Author(s):  
DongHyang Kwon ◽  
Shira Ronen ◽  
Alessio Giubellino ◽  
Elizabeth Keiser ◽  
Phyu P. Aung ◽  
...  

4open ◽  
2019 ◽  
Vol 2 ◽  
pp. 23 ◽  
Author(s):  
Mariya Yurievna Pakharukova ◽  
José Manuel Correia da Costa ◽  
Viatcheslav Alekseevitch Mordvinov

Opisthorchiasis caused by the liver fluke Opisthorchis felineus is one of the most common helminthic infections in the Russian Federation. The largest area affected by opisthorchiasis felinea occupies almost the entire territory of Western Siberia and extends to northern Kazakhstan and a part of the Ural region. Natural endemic regions of opisthorchiasis also exist in the European part of Russia, and in the regions of Western and Eastern Europe. According to the official statistics of the Russian Federation, up to 40 000 patients with opisthorchiasis are registered annually in the country. Opisthorchiasis felinea affects the hepatobiliary system and causes serious liver disorders, including cancer of the biliary tract. Other parasitoses, opisthorchiasis viverrini and clonorchiasis, are widespread in the Southeast Asia and China. The causative agents of these diseases, liver flukes O. viverrini and Clonorchis sinensis, are officially recognized as Group 1 biological carcinogens and are classified as the main risk factors for cholangiocarcinoma. O. felineus is included in Group 3 of biological carcinogens and is not officially considered carcinogenic to humans. Studies on the carcinogenic potential of this liver fluke and the epidemiology of cholangiocarcinoma in the Russian Federation have started in earnest quite recently. Nevertheless, we have some evidence that infection with O. felineus leads to a precancerous state of the bile duct epithelium. This state, combined with additional risk factors, poses a real risk of cholangiocarcinoma. In our opinion, taking into consideration the accumulated facts, the classification of the carcinogenic potential of O. felineus requires revision. In this review, we focus on the relevant characteristics of the biology and epidemiology of this helminth as well as experimental data on opisthorchiasis felinea; this information might clarify the carcinogenicity of O. felineus to humans.


2019 ◽  
Author(s):  
Maria João Gouveia ◽  
Maria Y. Pakharukova ◽  
Banchob Sripa ◽  
Gabriel Rinaldi ◽  
Paul J. Brindley ◽  
...  

AbstractChronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in this list of biological carcinogens. By contrast, infections with close phylogenetic relatives including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here we employed liquid chromatography-mass spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis species included far fewer compounds than F. hepatica. These findings support the postulate that oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a molecular basis for the inconsistencies among major groups of liver flukes concerning infection-induced malignancy.Author SummarySeveral species of trematodes are parasites of the human hepatobiliary tract. Infection with two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the current findings is informative because they present a mass spectrometric analysis and catalog of the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be expected to provide deeper understanding of helminth infection induced malignancy.


Author(s):  
Caiqin Wang ◽  
Qing He ◽  
Yingxuan Yin ◽  
Yinjuan Wu ◽  
Xuerong Li

The biological functions of growth factor, such as granulins, have been explored in parasites, and we elucidated that Clonorchis sinensis granulin (CsGRN) promoted the metastasis of hepatocellular carcinoma in our previous study. However, it is still unclear for the malignant transformation role of CsGRN in normal human hepatocytes. In this study, by transfecting pEGFP-C1-CsGRN eukaryotic expression plasmid, a cell line with stable overexpression of CsGRN in normal hepatocyte (LO2-GRN cells) was constructed. The effects on cell proliferation were detected by carrying out cell counting kit-8 (CCK8) assay and colony formation assay. Additionally, we conducted flow cytometry analysis to determine whether the proliferation of CsGRN was due to cell cycle arrest. Subsequently, the migration ability and the invasion ability of LO2-GRN cells were evaluated through wound-healing assay and transwell assay. Meanwhile, the levels of the markers of RAS/MAPK/ERK and PI3K/Akt signaling pathways activation in LO2-GRN cells were assessed by quantitative RT-PCR and Western blot. Our results indicated that CsGRN promoted the proliferation of LO2 cells by regulating the expression of cell-cycle-related genes. Moreover, the overexpression of CsGRN regulates malignant metastasis of liver cells by inducing the upregulation of epithelial–mesenchymal transition (EMT) marker proteins. Furthermore, both mRNA and protein expression levels of p-EGFR, RAS, p-ERK, p-AKT, p-PI3K, and p-braf have been enhanced by CsGRN. These results showed that CsGRN promoted the malignant transformation of hepatocytes by regulating epidermal growth factor receptor (EGFR)-mediated RAS/MAPK/ERK and PI3K/Akt signaling pathways, which suggested that CsGRN could serve as a novel oncoprotein during Clonorchis sinensis–associated malignant transformation of hepatocytes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Y. Pakharukova ◽  
Oxana Zaparina ◽  
Sung-Jong Hong ◽  
Banchob Sripa ◽  
Viatcheslav A. Mordvinov

AbstractHelicobacter pylori causes a wide range of human diseases including cancer. Carcinogenic foodborne trematodes Opisthorchis viverrini, Clonorchis sinensis, and O. felineus might promote transmission and spread of H. pylori infection in the definitive mammalian host, which in turn might contribute to the liver fluke-associated malignancy. Our objectives were to find out whether liver flukes O. felineus, O. viverrini, and C. sinensis are carriers of Helicobacter pylori and to determine whether H. pylori is present in feces, bile, and stomach samples from the experimentally infected hamsters. We found that liver flukes are not reservoirs of H. pylori. Nevertheless, the prevalence of H. pylori and the H. pylori ureA gene copy number were significantly elevated after the infection. Overall, although the liver flukes O. felineus, C. sinensis, and O. viverrini are not reservoirs of H. pylori, the infection with the liver flukes significantly modifies the biliary and gut microbiota by increasing H. pylori abundance. This may be a feature of any liver fluke pathogenesis that have not previously been taken into account. Our findings appear to be novel in terms of comparative assessment of the host microbiota and Helicobacter abundance during epidemiologically important liver fluke infections.


Sign in / Sign up

Export Citation Format

Share Document