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Introduction to Cancer
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Certain parasitic worms are known to be carcinogenic. These include Clonorchis sinensis (the organism causing Clonorchiasis) and Opisthorchis viverrini (causing Opisthorchiasis), which have both been associated with cholangiocarcinoma. In addition, Schistosoma species (the organisms causing Schistosomiasis) have been associated with bladder cancers. For example, Schistosoma haematobium is a highly prevalent blood fluke and human parasite with a proven link to malignant bladder cancer.
Opisthorchis viverrini
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
T. Boonmars, R. Aukkanimart, P. Sriraj, S. Boonjaraspinyo, P. Luamuanwai, J. Songsri, P. Sripan
O. viverrini causes chronic inflammation around the biliary tract, with severe hyperplasia of the cholangiocytes that line the biliary tract proximal to the flukes. Metaplasia of the biliary epithelial cells into mucin-producing cells occurs early during the infection, as these cells proliferate to produce small gland-like structures in the mucosa, leading to persistent and excessive mucus in the bile.14,61,65 Severity of this periductal fibrosis correlates with the duration of infection,1,14 the parasite burden,66 and genetic susceptibility of the host.61,67–69 The host immune response mediates much of the hepatobiliary damage in opisthorchiasis.13 As with other causes of chronic inflammation, persistent irritants sustain the simultaneous production of growth factors and fibrogenic cytokines, which in turn stimulate the deposition of connective tissue that progressively remodels and destroys the normal tissue architecture of the biliary epithelium, resulting in the accumulation of fibrotic elements.70–72 Chronic infection with O. viverrini alone cannot induce cholangiocarcinoma development: infection must be combined with other factors (consumption of alcohol, steroidal drugs, and nitrosamine in fermented foods) for cholangiocarcinoma to develop.13,14,28
Praziquantel
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Pyrazinoisoquinoline derivatives were first evaluated by Merck in the 1970s as potential tranquilizers before being passed on to Bayer and subject to a veterinary screening process (Groll, 1984). Praziquantel was found to be active against a wide range of trematode and cestode helminths (Andrews et al., 1983), and was the most active of a group of over 400 related compounds. The drug was initially developed for veterinary use before being developed for use in humans. Praziquantel is currently the mainstay of treatment for schistosomiasis and opisthorchiasis.
Fish-borne trematode infections in wild fishes in Bangladesh
Published in Pathogens and Global Health, 2020
Sharmin S. Labony, M. Abdul Alim, Muhammad Mehedi Hasan, Md. Shahadat Hossain, Ausraful Islam, Mohammad Zahangir Alam, Naotoshi Tsuji
More than 45 million people are affected globally only with opisthorchiasis, diseases caused by opisthorchid flukes. Of the opisthorchid flukes, Clonorchis sinensis, the most important liver fluke, affects 15 million people only in East Asia, including 13 million in China and 1 million in northern Vietnam [7,8]. Historically, although C. sinensis infection was highly endemic in Japan, only a few cases have recently been reported; however, approximately 1.2 million individuals are infected in South Korea [8]. On the other hand, 8.6 million people have been infected with Opisthorchis viverrini in Southeast Asian countries, approximately 6 million of whom were in Thailand [9]. Additionally, 1.6 million individuals are infected with O. felineus globally, including 1.5 million in the former Union of Soviet Socialist Republics [10]. According to Nguyen et al. [4], more than 750 million individuals are at risk to fish borne liver flukes throughout Asia. Furthermore, 40–50 million individuals have been affected with one or more species of fish-borne intestinal flukes and approximately half a billion individuals are at risk globally [11]. In a recent study, the disability-adjusted life years (DALYs) of FBTs had been reported to be 1.8 million, and estimated to have increased by 8.5% within 2007–2017 [12]. FBTs, particularly liver flukes, have been implicated in biliary tract obstruction, bile flux block, and icterus [13]. Infections by intestinal flukes cause fatigue and mild gastrointestinal symptoms, such as epigastric pain, anorexia, and diarrhea, however, in severe infections they cause abdominal cramps, malabsorption, and weight loss [14].
Novel and emerging targets for cholangiocarcinoma progression: therapeutic implications
Published in Expert Opinion on Therapeutic Targets, 2022
Lionel A. Kankeu Fonkoua, Pedro Luiz Serrano Uson Junior, Kabir Mody, Amit Mahipal, Mitesh J. Borad, Lewis R. Roberts
The carcinogenic etiology of CCA may also present distinct radiographic features that may be helpful in attaining an early diagnosis and treatment, particularly for OV-induced CCA. Several US features of opisthorchiasis have been identified and associated with progression of CCA, including hepatomegaly, periductal fibrosis, intrahepatic lithiasis, gallstone, gallbladder sludge and poor gallbladder contraction [31–33]. Given the correlation between the degree of pathogenicity and clinical involvement of OV infection, reversal of these radiographic features have been observed with praziquantel treatment[34]. Population-based OV screening and monitoring of at-risk patients would be a logical strategy for early CCA detection but no randomized trial to date has shown a clear benefit of this approach. Until a preventive intervention is implemented, it is imperative that screening and monitoring programs adapted to etiological factors endemic to each area be developed. The Cholangiocarcinoma Screening and Care Program (CASCAP) is one such programs launched in northeast Thailand, an area with a very high incidence of OV-related CCA[35]. In this ongoing prospective cohort study, the use of US evaluation in conjunction with stool density of OV eggs is proving to be a powerful tool for screening and early intervention. While microscopy-based stool examination remains the ‘gold standard’ diagnostic technique for OV infection, an enzyme-linked immunosorbent assay (ELISA) was recently developed for Ov excretory-secretory (ES) antigen detection in urine samples and exhibits much better diagnostic sensitivity and specificity [36–38]. This urine Ov-ES antigen assay has the potential to be a better companion diagnostic test for OV-induced CCA, in conjunction with US.
Recent trends in praziquantel nanoformulations for helminthiasis treatment
Published in Expert Opinion on Drug Delivery, 2022
Ana C. Mengarda, Bruno Iles, João Paulo F. Longo, Josué de Moraes
Chemotherapy is the main method for controlling infections caused by flatworms, but although helminthiases can cause significant mortality and devastating social and economic consequences, few drugs are available to treat flatworm infections. Since its discovery in the 1970s, the pyrazinoisoquinoline derivative praziquantel (PZQ, Figure 1) has replaced many other drugs as the sole treatment for a range of flatworm infections in humans and animals worldwide [7]. PZQ has potent cestocidal activity against species of Taenia, Echinococcus, Mesocestoides, Dipylidium, and Hymenolepis. It crosses the blood-brain barrier, which explains its effectiveness in neurocysticercosis [8]. PZQ is also highly effective against food-borne trematodiasis such as paragonimiasis, clonorchiasis, and opisthorchiasis (Figure 2). In addition, PZQ is effective against all species of the trematode worm Schistosoma and it is the mainstay of mass drug administration programs. Schistosomiasis transmission has already been reported in 78 countries, and recent estimates show that at least 236.6 million people required preventive treatment with PZQ [9]. However, because schistosomiasis has high re-infection rates, PZQ is administered every 6 to 12 months. PZQ is included in the World Health Organization (WHO) Model List of Essential Medicines for Children [9], but there is no oral formulation adapted for use by the youngest children. Fortunately, research on a pediatric formulation is ongoing by the Pediatric Praziquantel Consortium [10]. Effective treatment of schistosomiasis, and other flatworm infections, needs to become a healthcare priority, to reduce the impact and inequity of helminthiasis diseases, which are undeniably of global medical importance.