scholarly journals Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

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.

2020 ◽  
Vol 1 ◽  
Author(s):  
Maria João Gouveia ◽  
Maria Y. Pakharukova ◽  
Gabriel Rinaldi ◽  
Viatcheslav A. Mordvinov ◽  
Paul J. Brindley ◽  
...  

AbstractEarlier reports revealed oxysterol metabolites of Opisthorchis spp. 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 to investigate, compare and contrast spectrograms of soluble extracts from Fasciola hepatica adult worms from bile ducts of cattle with those from O. viverrini and O.felineus from experimentally infected hamsters. F. hepatica and Opisthorchis spp. shared common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of F. hepatica included far fewer compounds than Opisthorchis species. These findings support the postulate that parasitic oxysterol-like metabolites could be related to carcinogenesis associated to infection and they point to a molecular basis for the differences among major groups of liver flukes concerning infection-induced malignancy.


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 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.


2017 ◽  
Vol 17 (2) ◽  
pp. 94-103
Author(s):  
K. Lalchhandama

Three flukes, Schistosoma haematobium (urinary blood fluke), Clonorchis sinensis (Chinese liver fluke), and Opisthorchis viverrini (Southeast Asian liver fluke) are, by official decree, Group 1 (fully proven) human carcinogens. Thus, they comprise a group of preventable carcinogens. But considering the situation of prevailing infection, from the lifestyle and food habits of people in the endemic regions, it is unlikely that they are eradicated in the near future. S. haematobium is transmitted by snails and infection is acquired from snail-infested water. C. sinensis and O. viverrini are both transmitted from eating fish. As medically important flukes, it is crucial to understand their biology, and this is an attempt to explain that in the light of the history of their discovery. Further, this is written with a hope that several facts, often erroneously presented in scientific literature, about these flukes are rectified.


2017 ◽  
Vol 17 (2) ◽  
pp. 78-93
Author(s):  
K. Lalchhandama

Cancer is multifaceted and multifarious disease. The diversity of cancer is complicated by so many types of carcinogens. Remarkably, helminth parasites are among the first well-established cancer agents. It started with the celebrated discovery of a roundworm Gongylonema neoplasticum (more famously, but wrongly, as Spiroptera carcinoma) by Johannes Fibiger, only to show that Nobel Prize selection can be a fallible operation. After almost a century of scepticism, it is now conceded that helminths, other than G. neoplasticum, are truly carcinogenic. For the first time in history, the International Agency for Research on Cancer finally proclaimed in 2009 that three flukes, Schistosoma haematobium (urinary blood fluke), Clonorchis sinensis (Chinese liver fluke), and Opisthorchis viverrini (Southeast Asian liver fluke) are Group 1, i.e. fully proven, carcinogens. The first is the leading cause of bladder cancer, while the latter two are of that of the bile duct (cholangiocarcinoma). This is the story of how they came to be.


2007 ◽  
Vol 388 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Sean L. Russell ◽  
Neil V. McFerran ◽  
Elizabeth M. Hoey ◽  
Alan Trudgett ◽  
David J. Timson

Abstract Calmodulin is a calcium ion-sensing signalling protein found in eukaryotics. Two calmodulin-like gene sequences were identified in an EST library from adult liver flukes. One codes for a protein (FhCaM1) homologous to mammalian calmodulins (98% identity), whereas the other protein (FhCaM2) has only 41% identity. These genes were cloned into expression vectors and the recombinant proteins were expressed in Escherichia coli. Gel shift assays showed that both proteins bind to calcium, magnesium and zinc ions. Homology models have been built for both proteins. As expected, FhCaM1 has a highly similar structure to other calmodulins. Although FhCaM2 has a similar fold, its surface charge is higher than FhCaM1. One of the potential metal ion-binding sites has lower metal-ion co-ordination capability, while another has an adjacent lysine residue, both of which may decrease the metal-binding affinity. These differences may reflect a specialised role for FhCaM2 in the liver fluke.


1974 ◽  
Vol 11 (5) ◽  
pp. 407-416 ◽  
Author(s):  
A. H. Cheema

Gall bladders from 80 mature cattle infested with liver flukes were shrunken; their walls were thickened; and mucosa was raised into rugose folds, nodules and papillary projections. All contained thick bile and mature liver flukes, predominantly Fasciola gigantica and to a lesser extent Fasciola hepatica. There was an adenomatous proliferation of the lining epithelium as well as of submucosal glands forming numerous tubuloalveolar structures and cysts lined with a uniform layer of columnar epithelium. Fibrous stroma was more than normal, and there was a mild to heavy infiltration by inflammatory cells. Some bladders had many enterochromaffin cells in the epithelium lining the glandular structures. Mitotic figures were rare, and there was no evidence of malignancy. The condition is inflammatory and hyperplastic and is believed to be common in cattle infested with liver fluke. The clinical effects of this condition have not been studied.


2013 ◽  
Vol 89 (2) ◽  
pp. 255-256 ◽  
Author(s):  
Y. Nawa ◽  
P.N. Doanh ◽  
U. Thaenkham

AbstractRecently, in the Journal of Helminthology (May 2013), Dao et al. reported that Opisthorchis viverrini-like flukes were found in the bile duct of domestic ducks in Vietnam. They stated that this is the first record of Opisthorchis sp. in birds in Vietnam. However, three Opisthorchis species – O. cheelis, O. longissimus and O. parageminus – in birds in Vietnam were described by Le in 2000. Amongst these, O. parageminus was first reported, by Oshmarin in 1970, as a new Opisthorchis species found in domestic ducks (Anas platyrhynchos) in Vietnam. Morphologially O. viverrini-like flukes described by Dao et al. are much more similar to O. parageminus than to O. viverrini. The phylogenetic trees of internal transcribed spacer 2 (ITS2) and cytochrome oxidase 1 (CO1) gene sequences also showed that the O. viverrini-like liver flukes from domestic ducks were closer to O. lobatus than to O. viverrini. Therefore, O. viverrini-like liver flukes reported by Dao et al. (2013) are most likely to be O. parageminus.


2006 ◽  
Vol 51 (3) ◽  
pp. 1096-1098 ◽  
Author(s):  
Jennifer Keiser ◽  
Xiao Shu-Hua ◽  
Jacques Chollet ◽  
Marcel Tanner ◽  
Jürg Utzinger

ABSTRACT We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica.


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.


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