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Goksen S, Varan G, Bilensoy E, Esendagli G. Folate Receptor β (FRβ) Expression on Myeloid Cells and the Impact of Reticuloendothelial System on Folate-Functionalized Nanoparticles' Biodistribution in Cancer. Mol Pharm 2024; 21:4688-4699. [PMID: 39105761 PMCID: PMC11372836 DOI: 10.1021/acs.molpharmaceut.4c00663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 07/27/2024] [Accepted: 07/30/2024] [Indexed: 08/07/2024]
Abstract
Folate uptake is largely mediated by folate receptor (FR)β, encoded by FOLR2 gene, in myeloid immune cells such as granulocytes, monocytes, and especially in macrophages that constitute the reticuloendothelial system (RES) and infiltrate the tumor microenvironment. Since the myeloid immune compartment dynamically changes during tumorigenesis, it is critical to assess the infiltration status of the tumors by FRβ-expressing myeloid cells to better define the targeting efficacy of folate-functionalized drug delivery systems. On the other hand, clearance by RES is a major limitation for the targeting efficacy of nanoparticles decorated with folate. Therefore, the aims of this study are (i) to determine the amount and subtypes of FRβ+ myeloid cells infiltrating the tumors at different stages, (ii) to compare the amount and subtype of FRβ+ myeloid cells in distinct organs of tumor-bearing and healthy animals, (iii) to test if the cancer-targeting efficacy and biodistribution of a prototypic folate-functionalized nanoparticle associates with the density of FRβ+ myeloid cells. Here, we report that myeloid cell infiltration was enhanced and FRβ was upregulated at distinct stages of tumorigenesis in a mouse breast cancer model. The CD206+ subset of macrophages highly expressed FRβ, prominently both in tumor-bearing and healthy mice. In tumor-bearing mice, the amount of all myeloid cells, but particularly granulocytes, was remarkably increased in the tumor, liver, lungs, spleen, kidneys, lymph nodes, peritoneal cavity, bone marrow, heart, and brain. Compared with macrophages, the level of FRβ was moderate in granulocytes and monocytes. The density of FRβ+ immune cells in the tumor microenvironment was not directly associated with the tumor-targeting efficacy of the folate-functionalized cyclodextrin nanoparticles. The lung was determined as a preferential site of accumulation for folate-functionalized nanoparticles, wherein FRβ+CD206+ macrophages significantly engulfed cyclodextrin nanoparticles. In conclusion, our results demonstrate that the tumor formation augments the FR levels and alters the infiltration and distribution of myeloid immune cells in all organs which should be considered as a major factor influencing the targeting efficacy of nanoparticles for drug delivery.
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Affiliation(s)
- Sibel Goksen
- Department
of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara 06100, Türkiye
| | - Gamze Varan
- Department
of Vaccine Technology, Hacettepe University
Vaccine Institute, Ankara 06100, Türkiye
| | - Erem Bilensoy
- Department
of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Türkiye
| | - Gunes Esendagli
- Department
of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara 06100, Türkiye
- Department
of Vaccinology, Hacettepe University Vaccine
Institute, Ankara 06100, Türkiye
- Department
of Basic Oncology, Hacettepe University
Cancer Institute, Ankara 06100, Türkiye
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Hu YW, Zhao YL, Yan JX, Ma CK. Coexistence of liver abscess, hepatic cystic echinococcosis and hepatocellular carcinoma: A case report. World J Clin Cases 2024; 12:2404-2411. [PMID: 38765738 PMCID: PMC11099406 DOI: 10.12998/wjcc.v12.i14.2404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/07/2020] [Accepted: 04/03/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.
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Affiliation(s)
- Ya-Wen Hu
- Department of Interventional Therapy, The Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Yi-Lin Zhao
- Department of Interventional Therapy, The Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Jing-Xin Yan
- West China Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
| | - Cun-Kai Ma
- Department of Interventional Therapy, The Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
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Schreiber M, Vajs V, Horák P. How tapeworms interact with cancers: a mini-review. PeerJ 2024; 12:e17196. [PMID: 38563013 PMCID: PMC10984186 DOI: 10.7717/peerj.17196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 03/14/2024] [Indexed: 04/04/2024] Open
Abstract
Cancer is one of the leading causes of death, with an estimated 19.3 million new cases and 10 million deaths worldwide in 2020 alone. Approximately 2.2 million cancer cases are attributed to infectious diseases, according to the World Health Organization (WHO). Despite the apparent involvement of some parasitic helminths (especially trematodes) in cancer induction, there are also records of the potential suppressive effects of helminth infections on cancer. Tapeworms such as Echinococcus granulosus, Taenia crassiceps, and more seem to have the potential to suppress malignant cell development, although in a few cases the evidence might be contradictory. Our review aims to summarize known epidemiological data on the cancer-helminth co-occurrence in the human population and the interactions of tapeworms with cancers, i.e., proven or hypothetical effects of tapeworms and their products on cancer cells in vivo (i.e., in experimental animals) or in vitro. The prospect of bioactive tapeworm molecules helping reduce the growth and metastasis of cancer is within the realm of future possibility, although extensive research is yet required due to certain concerns.
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Affiliation(s)
- Manfred Schreiber
- Department of Parasitology, Faculty of Science, Charles University Prague, Prague, Czech Republic
| | - Vojtěch Vajs
- Department of Parasitology, Faculty of Science, Charles University Prague, Prague, Czech Republic
| | - Petr Horák
- Department of Parasitology, Faculty of Science, Charles University Prague, Prague, Czech Republic
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4
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Sadr S, Borji H. Echinococcus granulosus as a Promising Therapeutic Agent against Triplenegative Breast Cancer. CURRENT CANCER THERAPY REVIEWS 2023; 19:292-297. [DOI: 10.2174/1573394719666230427094247] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 11/06/2022] [Accepted: 01/19/2023] [Indexed: 08/19/2024]
Abstract
Abstract:Breast cancer is a major cause of cancer deaths in women, with approximately 1.2 million new cases per year. Current treatment options for breast cancer include surgery, radiation, hormone therapy, and chemotherapy. However, the non-selective cytotoxicity of chemotherapeutic agents often leads to severe side effects, while drug resistance can worsen patient outcomes. Therefore, the development of more effective and less toxic anticancer drugs is a critical need. This study aimed to review the literature on Echinococcus granulosus antigens with anticancer potential against triple-negative breast cancer. Recent studies have suggested that certain parasite antigens may have potential anticancer effects. Specifically, research has shown that echinococcosis, a disease caused by the parasitic cestode Echinococcus granulosus, may have a protective effect against cancer. These findings offer new insights into the potential use of E. granulosus antigens in the development of novel cancer therapies and tumor cell vaccines. The findings of recent studies suggested that E. granulosus antigens may have the potential to be used in effective and less toxic cancer treatments. However, further research is needed to fully understand the mechanisms behind the anticancer effects of these antigens and develop new cancer therapies and vaccines
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Affiliation(s)
- Soheil Sadr
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Hassan Borji
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
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5
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Yousefi M, Akbari M, Hadipour M, Dehkordi AB, Farahbakhsh Z, Darani HY. Parasites as potential targets for cancer immunotherapy. J Cancer Res Clin Oncol 2023; 149:8027-8038. [PMID: 36949175 DOI: 10.1007/s00432-023-04694-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/13/2023] [Indexed: 03/24/2023]
Abstract
Parasites and cancers have some common antigens. Much scientific evidence in the human population, animal models, and in vitro experiments exhibit that parasites have significant anti-cancer effects. The larval stage of the tapeworm Echinococcus granulosus, Toxoplasma gondii, Trypanosoma cruzy, Plasmodium's, and Trichinella spiralis are among the parasites that have been subjects of anti-cancer research in the last decades. Anti-tumor effects of parasites may be due to the direct impact of the parasites per se or indirectly due to the immune response raised against common antigens between malignant cells and parasites. This manuscript reviews the anti-cancer effects of parasites and possible mechanisms of these effects. Options for using parasites or their antigens for cancer treatment in the future have been discussed.
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Affiliation(s)
- Morteza Yousefi
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadesmail Akbari
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mahboubeh Hadipour
- Department of Parasitology and Mycology, Faculty of Medicine, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Azar Balouti Dehkordi
- Department of Parasitology and Mycology, Faculty of Medicine, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zohreh Farahbakhsh
- Department of Parasitology and Mycology, Faculty of Medicine, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hossein Yousofi Darani
- Department of Parasitology and Mycology, Faculty of Medicine, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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6
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Yasen A, Ran B, Wang M, Lv G, Lin R, Shao Y, Aji T, Wen H. Roles of immune cells in the concurrence of Echinococcus granulosus sensu lato infection and hepatocellular carcinoma. Exp Parasitol 2022; 240:108321. [PMID: 35787385 DOI: 10.1016/j.exppara.2022.108321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 11/26/2022]
Abstract
Immune cells are pivotal players in the immune responses against both parasitic infection and malignancies. Substantial evidence demonstrated that there may exist possible relationship between echinococcus granulus sensu lato (E. granulosus s.l.) infection and hepatocellular carcinoma (HCC) development. Thus, this study aimed to observe crucial roles of immune cells in the formation of subcutaneous lesions after transplanting HepG2 cell lines with or without E. granulosus s.l. protoscoleces (PSCs). HepG2 cell lines were subcutaneously injected into nude mice in the control group. In the co-transplantation group, HepG2 cells were subcutaneously co-injected with high dosage of E. granulosus s.l. PSCs. From the 25th day of transplantation, volume of subcutaneous lesions was measured every four days, which were removed at the 37th day for further studies. Basic pathological and functional changes were observed. Moreover, expression of Ki67, Bcl-2, Caspase3, α-smooth muscle actin (α-SMA), T cell markers (CD3, CD4, CD8), PD1/PD-L1, nature killer (NK) cell markers (CD16, CD56) were further detected by immunohistochemical staining and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Subcutaneous lesions were gradually increased in volume and there occurred pathologically heterogeneous tumor cells, which were more significant in the co-transplantation group. Compared to the control group, expression of proliferation markers Ki67 and Bcl-2 was at higher levels in the co-transplantation group. Reversely, apoptotic marker Caspase3 was highly detected in the control group, suggesting promoting effects of E. granulosus s.l. PSCs on HCC development. Interestingly, subcutaneous lesions of the co-transplantation group were more functional in synthesizing and storing glycogen. Collagen and α-SMA+ cells were also at higher levels in the co-transplantation group than those in the control group. Most importantly, co-transplantation of HepG2 cells with E. granulosus s.l. PSCs led to significant increase in the expression of T cell markers, PD1/PD-L1 and NK cells markers. E. granulosus s.l. may have promoting effects on HCC development, which was closely associated with the immune responses of T cells and NK cells.
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Affiliation(s)
- Aimaiti Yasen
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, 830054, Urumqi, Xinjiang, China
| | - Bo Ran
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China
| | - Maolin Wang
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China
| | - Guodong Lv
- Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China
| | - Renyong Lin
- Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China
| | - Yingmei Shao
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China.
| | - Tuerganaili Aji
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, 830054, Urumqi, Xinjiang, China.
| | - Hao Wen
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, 830054, Urumqi, Xinjiang, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, 830054, Urumqi, Xinjiang, China.
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7
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Hepatocellular Carcinoma Presenting Simultaneously with Echinococcal Cyst Mimicking a Single Liver Lesion in a Non-Cirrhotic Patient: A Case Report and Review of the Literature. Diagnostics (Basel) 2022; 12:diagnostics12071583. [PMID: 35885489 PMCID: PMC9322078 DOI: 10.3390/diagnostics12071583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/19/2022] [Accepted: 06/25/2022] [Indexed: 11/26/2022] Open
Abstract
A coexistance of liver cystic echinococcosis (CE) and hepatocellular carcinoma (HCC) is very rare. HCC is the leading cause of cancer-related mortality worldwide, while CE is a globally endemic zoonosis caused by the cestode tapeworm Echinococcus granulosus. The association between these two diseases is still not well-defined. A preoperative diagnosis may be challenging, especially if HCC and CE present as a single lesion and if atypical imaging features are present. Herein, we present a case of the patient that was initially diagnosed as an extensive necrotic tumor in the left liver lobe and highly suspicious of being HCC associated with peritumoral hematoma. Left hemihepatectomy was performed, and the histopathological findings showed the collision of two lesions: a hydatid cyst and HCC.
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8
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Mohammadi M, Spotin A, Mahami-Oskouei M, Shanehbandi D, Ahmadpour E, Casulli A, Rostami A, Baghbanzadeh A, Asadi M. MicroRNA-365 promotes apoptosis in human melanoma cell A375 treated with hydatid cyst fluid of Echinococcus granulosus sensu stricto. Microb Pathog 2021; 153:104804. [PMID: 33609644 DOI: 10.1016/j.micpath.2021.104804] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 02/09/2021] [Accepted: 02/10/2021] [Indexed: 11/18/2022]
Abstract
Hydatid cyst fluid (HCF)-based therapeutics has experimentally targeted approaches for treating human cancer cell lines. MicroRNA-365 (miR-365) has been reported to be an important tumor suppressor miRNA in cancers. However, it remains unknown, how miR-365 plays a pivotal role in inducing apoptosis in HCF-treated cancer cells in vitro. The fertile/infertile HCF was aspirated from liver of infected sheep and in terms of molecular taxonomy was identified as G1 genotype of Echinococcus granulosus sensu stricto. A375 human melanoma cancer cells were cultured into two groups: fertile and infertile HCF-treated A375 cells. To assess the cytotoxicity of various concentrations of HCF on melanoma cells, cell viability was determined by using MTT assay. The IC50 value of HCF on A375 cells was determined 85 μg/mL. Caspase-3 enzymatic activity was evaluated by fluorometric assay in the HCF-treated melanoma cells. In addition, the mRNA expression of Bax, Bcl-2, Caspase-9 and miR-365 were determined by qRT-PCR. Findings of MTT assay showed that concentrations 85 μg/mL to 100 μg/mL of fertile HCF have the highest mortality (50%-52%) on A375 cells during 24 h. The fold change of Bax/Bcl-2 ratio, Caspase-9, miR-365 and Caspase-3 activity was higher in the fertile HCF-treated melanoma cells compared to infertile fluid treated A375 cells and human normal epithelial cell (as control cell). In conclusion, we over-expressed the miR-365 in melanoma A375 cells, via treatment of fertile HCF. Our findings suggested that inducing high expression of miR-365 might be a negative regulator of melanoma growth through activation of pro-apoptotic Bax, Caspase-9 and Caspase-3 that are essential to intrinsic apoptotic pathway. These findings provide new insights into the use of Echinococcus HCF-derived metabolites in the design of drug therapies and in vivo tumor cell vaccine to combat melanoma progression.
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Affiliation(s)
- Mahnaz Mohammadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Adel Spotin
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mahmoud Mahami-Oskouei
- Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Dariush Shanehbandi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ehsan Ahmadpour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Adriano Casulli
- WHO Collaborating Centre for the Epidemiology, Detection and Control of Cystic and Alveolar Echinococcosis, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy; European Union Reference Laboratory for Parasites (EURLP), Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Ali Rostami
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Milad Asadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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9
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Yasen A, Wang M, Ran B, Lv G, Aji T, Xiao H, Shao Y, Wen H. Echinococcus granulosus protoscoleces promotes proliferation and invasion of hepatocellular carcinoma cells. Cytotechnology 2021; 73:13-22. [PMID: 33505110 PMCID: PMC7817750 DOI: 10.1007/s10616-020-00437-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 10/30/2020] [Indexed: 10/23/2022] Open
Abstract
There may exist a connection between Echinococcus granulosus infection and cancer development. Here, it is aimed to investigate specific effects of E. granulosus protoscoleces (PSCs) on the proliferation and invasion capacities of hepatocellular carcinoma (HCC) cells in vitro and ex vitro. HepG2 cells were cultured with different quantities of E. granulosus PSCs in vitro. MTT analysis was used to evaluate effects of E. granulosus PSCs on the proliferation of HepG2 cells. Besides, scratch and transwell assays were respectively used for the detection of HepG2 cells migration and invasion capacities after co-culture with E. granulosus PSCs. Then, HepG2 cells were subcutaneously transplanted into nude mice with or without E. granulosus PSCs. From the 25th day of transplantation, the volume of subcutaneous lesions was measured every four days. At the 37th day, subcutaneous lesions were removed and their weight was evaluated. H&E staining was used for detecting basic pathological changes. HepG2 cells grew well without obvious morphological changes. Proliferation rate and migration capacity of HepG2 cells were higher in the co-culture group than the control group, which was closely associated with quantities of E. granulosus PSCs and co-culture time length. Moreover, HepG2 cells co-cultured with E. granulosus PSCs had stronger invasion ability than the control HepG2 cells. Importantly, there existed significant differences in the volume and weight of subcutaneous lesions after transplanting HepG2 cells with E. granulosus PSCs than the control group. HepG2 cells were also more pathologically heterogeneous in morphology after transplantation with E. granulosus PSCs. Thus, E. granulosus PSCs may promote proliferation and invasion of HCC cells.
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Affiliation(s)
- Aimaiti Yasen
- Hepatobiliary and Hydatid Disease Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
- The First Clinical College of Xinjiang Medical University, Urumqi, 830011 Xinjiang People’s Republic of China
| | - Maolin Wang
- Hepatobiliary and Hydatid Disease Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
- The First Clinical College of Xinjiang Medical University, Urumqi, 830011 Xinjiang People’s Republic of China
| | - Bo Ran
- The First Clinical College of Xinjiang Medical University, Urumqi, 830011 Xinjiang People’s Republic of China
- Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
- School of Public Health, Xinjiang Medical University, Urumqi, 830011 Xinjiang People’s Republic of China
| | - Guodong Lv
- Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
| | - Tuerganaili Aji
- Hepatobiliary and Hydatid Disease Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
- Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
| | - Hui Xiao
- School of Public Health, Xinjiang Medical University, Urumqi, 830011 Xinjiang People’s Republic of China
| | - Yingmei Shao
- Hepatobiliary and Hydatid Disease Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
- Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
| | - Hao Wen
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
- Hepatobiliary and Hydatid Disease Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054 Xinjiang People’s Republic of China
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10
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Porras-Silesky C, Mejías-Alpízar MJ, Mora J, Baneth G, Rojas A. Spirocerca lupi Proteomics and Its Role in Cancer Development: An Overview of Spirocercosis-Induced Sarcomas and Revision of Helminth-Induced Carcinomas. Pathogens 2021; 10:pathogens10020124. [PMID: 33530324 PMCID: PMC7911836 DOI: 10.3390/pathogens10020124] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 12/19/2022] Open
Abstract
Spirocerca lupi is a parasitic nematode of canids that induces a myriad of clinical manifestations in its host and, in 25% of infections, leads to the formation of sarcomas. The description of the protein composition of the excretory and secretory products (Sl-ESP) of S. lupi has shed light on its possible interactions with the host environment, including migration within the host and mechanisms of immunomodulation. Despite this, the process by which S. lupi induces cancer in the dog remains poorly understood, and some hypotheses have arisen regarding these possible mechanisms. In this review, we discuss the role of specific ESP from the carcinogenic helminths Clonorchis sinensis, Opisthorchis viverrini and Schistosoma haematobium in inducing chronic inflammation and cancer in their host’s tissues. The parasitic worms Taenia solium, Echinococcus granulosus, Heterakis gallinarum, Trichuris muris and Strongyloides stercoralis, which have less-characterized mechanisms of cancer induction, are also analyzed. Based on the pathological findings in spirocercosis and the mechanisms by which other parasitic helminths induce cancer, we propose that the sustained inflammatory response in the dog´s tissues produced in response to the release of Sl-ESP homologous to those of other carcinogenic worms may lead to the malignant process in infected dogs.
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Affiliation(s)
- Catalina Porras-Silesky
- Laboratory of Helminthology, Centro de Investigación en Enfermedades Tropicales, University of Costa Rica, 11501-2060 San José, Costa Rica; (C.P.-S.); (M.J.M.-A.); (J.M.)
| | - María José Mejías-Alpízar
- Laboratory of Helminthology, Centro de Investigación en Enfermedades Tropicales, University of Costa Rica, 11501-2060 San José, Costa Rica; (C.P.-S.); (M.J.M.-A.); (J.M.)
| | - Javier Mora
- Laboratory of Helminthology, Centro de Investigación en Enfermedades Tropicales, University of Costa Rica, 11501-2060 San José, Costa Rica; (C.P.-S.); (M.J.M.-A.); (J.M.)
| | - Gad Baneth
- Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 7610001, Israel;
| | - Alicia Rojas
- Laboratory of Helminthology, Centro de Investigación en Enfermedades Tropicales, University of Costa Rica, 11501-2060 San José, Costa Rica; (C.P.-S.); (M.J.M.-A.); (J.M.)
- Correspondence: ; Tel.: +506-2511-8644
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11
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Jiménez M, Hidalgo C, Stoore C, Corrêa F, Pereira I, Hernández M, Sáenz L, Benavides J, Ferreras MC, Royo M, Paredes R. Fasciola hepatica co-infection enhances Th1 immune response in the adventitial layer of non-fertile Echinococcus granulosus cysts. Vet Parasitol 2021; 290:109343. [PMID: 33422750 DOI: 10.1016/j.vetpar.2021.109343] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 12/24/2020] [Accepted: 12/27/2020] [Indexed: 11/18/2022]
Abstract
Cystic echinococcosis is a widespread zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus. In intermediary hosts, two types of echinococcal cysts can be found: fertile, which produce protoscoleces, the infective form of the parasite to dogs; and infertile, that do not present protoscoleces and therefore are not able to continue with the parasite life cycle. The adventitial layer, the local immune response against the cyst, plays an important role in cyst fertility. Grazing cattle can often feature Fasciola hepatica co-infection, a parasite known to modulate the host systemic immune response. In this work the cellular Th1/Th2 immune profiles were evaluated in the adventitial layer of fertile and non-fertile cysts with and without co-infection with Fasciola hepatica. Measuring with immunohistochemistry and qPCR in adventitial layer, we report that non-fertile cysts present higher levels of Th1 cytokines (IFN-γ (P < 0.0001) and TNF-α (P < 0.05)), and fertile cysts have higher levels of Th2 cytokines (IL-4 (P < 0.001)). Co-infection with Fasciola hepatica is associated with a decrease in the expression of IL-4 (P < 0.05) and an increase in the expression of IFN-γ (P < 0.0001) in the adventitial layer of fertile cysts. Non-fertile cysts were associated with higher levels of Th1 cytokines in the adventitial layer, with IFN-γ expression enhanced by F. hepatica co-infection (P < 0.0001), confirming that polyparasitism should be considered in the treatment and control of naturally infected cattle.
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Affiliation(s)
- Mauricio Jiménez
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile; Laboratorio de Biotecnología, LIMOR de Colombia S.A.S, Bogotá, Colombia
| | - Christian Hidalgo
- Instituto de Ciencias Agroalimentarias, Animales y Ambientales (ICA3), Universidad de O'Higgins, San Fernando, Chile
| | - Caroll Stoore
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Felipe Corrêa
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile; Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa
| | - Ismael Pereira
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Marcela Hernández
- Laboratorio de Biología Periodontal y Departamento de Patología y Medicina Oral, Facultad de Odontología, Universidad de Chile, Santiago, Chile
| | - Leonardo Sáenz
- Laboratory of Veterinary Vaccines, Department of Animal Biology, Faculty of Veterinary and Animal Science, Universidad de Chile, Santiago, Chile
| | - Julio Benavides
- Dpto de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-Universidad de León), Facultad de Veterinaria, Campus de Vegazana s/n, León, Spain
| | - M Carmen Ferreras
- Dpto de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-Universidad de León), Facultad de Veterinaria, Campus de Vegazana s/n, León, Spain
| | - Marcos Royo
- Dpto de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-Universidad de León), Facultad de Veterinaria, Campus de Vegazana s/n, León, Spain
| | - Rodolfo Paredes
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.
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12
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Omarova KG, Aleshina NI, Ponezhevа ZB, Gorelov AV, Maleev VV, Akimkin VG. [Risks of oncologic pathology in parasitosis at the present time]. TERAPEVT ARKH 2020; 92:82-85. [PMID: 33720610 DOI: 10.26442/00403660.2020.11.000710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 12/26/2020] [Indexed: 11/22/2022]
Abstract
An analysis of published literature data on the relationship of parasitic diseases and oncogenesis is carried out. Current knowledge about the association of parasitic infections and cancer formation has revealed several carcinogenic mechanisms, but the severity of the relationship between parasites and cancer formation (except for schistosome, opisthorchis and clonorchis) should be confirmed in future experimental and population studies.
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Affiliation(s)
| | | | | | | | - V V Maleev
- Central Research Institute of Epidemiology
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13
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Shakibapour M, Shojaie B, Yousofi Darani H. Immunization with Hydatid Cyst Wall Antigens Can Inhibit Breast Cancer through Changes in Serum Levels of Th1/Th2 Cytokines. Int J Prev Med 2020; 11:189. [PMID: 33815713 PMCID: PMC8000162 DOI: 10.4103/ijpvm.ijpvm_311_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 10/31/2019] [Indexed: 11/04/2022] Open
Abstract
Background Hydatid cysts are the larval stage of Echinococcus granulosus, which lead to humoral and cellular immune responses in hosts. Such immune responses play a key role in the inhibition of tumor growth and cancers. To test this hypothesis, it was attempted not only to examine the changes in serum level of some Th1 and Th2 cytokines but also to find relationships between the cytokines and cancer in 4T1 breast cancer-bearing mice immunized with hydatid cyst wall (HCW) antigens. Methods Six to eight-week-old Balb/c female mice were immunized with alum, PBS and HCW antigens, including crude extract of HCW (laminated layer) 28 and 27 kDa protein bands (upper and lower bands) and then challenged with 4T1 breast cancer cells. The amounts of IL2, TNF-α, IFN-γ (Th1 cytokines), and IL4 (Th2 cytokine) were estimated using ELISA. Correlations between these cytokines and cancer parameters (tumor growth, metastasis, and survival) were determined by Pearson's correlation coefficients. Results Overall, HCW antigens increased the amounts of IL2, TNF-α, IFN-γ, and IL4. Pearson's correlation coefficients indicated reverse relationships between changes in amounts of these cytokines and tumor growth/metastasis. However, except for IL-4, all cytokines had a direct relationship with mouse survival. Conclusions The results of this study indicated that the inhibition of breast tumor growth and metastasis and improvement of survival in 4T1 mice immunized with HCW antigens, especially laminated layer and 27 kDa protein band can occur through a rise in the levels of cytokines.
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Affiliation(s)
- Mahshid Shakibapour
- Department of Medical Parasitology and Mycology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Behrokh Shojaie
- Department of Medical Parasitology and Mycology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran
| | - Hossein Yousofi Darani
- Department of Medical Parasitology and Mycology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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14
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Proteomic analysis of plasma exosomes from Cystic Echinococcosis patients provides in vivo support for distinct immune response profiles in active vs inactive infection and suggests potential biomarkers. PLoS Negl Trop Dis 2020; 14:e0008586. [PMID: 33017416 PMCID: PMC7535053 DOI: 10.1371/journal.pntd.0008586] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Accepted: 07/10/2020] [Indexed: 02/07/2023] Open
Abstract
The reference diagnostic method of human abdominal Cystic Echinococcosis (CE) is imaging, particularly ultrasound, supported by serology when imaging is inconclusive. However, current diagnostic tools are neither optimal nor widely available. The availability of a test detecting circulating biomarkers would considerably improve CE diagnosis and cyst staging (active vs inactive), as well as treatments and follow-up of patients. Exosomes are extracellular vesicles involved in intercellular communication, including immune system responses, and are a recognized source of biomarkers. With the aim of identifying potential biomarkers, plasma pools from patients infected by active or inactive CE, as well as from control subjects, were processed to isolate exosomes for proteomic label-free quantitative analysis. Results were statistically processed and subjected to bioinformatics analysis to define distinct features associated with parasite viability. First, a few parasite proteins were identified that were specifically associated with either active or inactive CE, which represent potential biomarkers to be validated in further studies. Second, numerous identified proteins of human origin were common to active and inactive CE, confirming an overlap of several immune response pathways. However, a subset of human proteins specific to either active or inactive CE, and central in the respective protein-protein interaction networks, were identified. These include the Src family kinases Src and Lyn, and the immune-suppressive cytokine TGF-β in active CE, and Cdc42 in inactive CE. The Src and Lyn Kinases were confirmed as potential markers of active CE in totally independent plasma pools. In addition, insights were obtained on immune response profiles: largely consistent with previous evidence, our observations hint to a Th1/Th2/regulatory immune environment in patients with active CE and a Th1/inflammatory environment with a component of the wound healing response in the presence of inactive CE. Of note, our results were obtained for the first time from the analysis of samples obtained in vivo from a well-characterized, large cohort of human subjects.
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15
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Zarbaliyev E, Hacısalihoğlu P. Surgical treatment of liver hydatid cyst before autologous stem cell transplantation; presentation of two cases with literature review. Transpl Infect Dis 2020; 23:e13450. [PMID: 32810324 DOI: 10.1111/tid.13450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/24/2020] [Accepted: 08/11/2020] [Indexed: 11/30/2022]
Abstract
Hydatid cyst, caused by Echinococcus granulosus, is a parasitic disease which is frequently seen in endemic areas. The disease can be seen as an isolated entity or simultaneously with other diseases. Treatment of hydatid cyst in patients with malignancy as well as in patients in need of transplantation is still unclear. Although there is information in the form of case reports, a large number of patient data are needed to create a consensus on the management of these patients. We reviewed two cases with the need of autologuous stem cell transplantation which underwent liver hydatic cystectomy before transplantation.
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Affiliation(s)
- Elbrus Zarbaliyev
- Department of General Surgery, Gaziosmanpaşa Hospital, Yeni Yüzyil University, İstanbul, Turkey
| | - Payam Hacısalihoğlu
- Department of Pathology, Gaziosmanpaşa Hospital, Yeni Yüzyil University, İstanbul, Turkey
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16
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Bo R, Yasen A, Shao Y, Zhang W, Lin R, Jiang T, Wen H, Xiao H, Aji T. Co-existence of hepatocellular carcinoma and cystic echinococcosis. Infect Agent Cancer 2020; 15:5. [PMID: 32010203 PMCID: PMC6988235 DOI: 10.1186/s13027-020-0275-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 01/16/2020] [Indexed: 02/08/2023] Open
Abstract
PURPOSE Co-existence of hepatocellular carcinoma (HCC) and cystic echinococcus (CE) is extremely rare. Echinococcus granulosus may exhibit a protective effect against cancer. Herein, this study aimed to evaluate the possible effects of echinococcal infection on HCC patients. METHODS Three thousand three hundred hepatic CE patients and 815 HCC patients were retrospectively reviewed between January 2010 and December 2018 in Xinjiang, China, and these patients were 1:5 matched according to their sex, age and tumor TMN stage, and only 13 patients coexisted both CE and HCC. Preoperative ultrasonography (US), computed tomography (CT), liver magnetic resonance imaging (MRI) and dot immune-gold filtration assay (DIGFA) were used for preoperative identification and intraoperative specimens from liver resections were pathologically examined for further confirmation. Survival time was analyzed through Cox proportional hazard model analysis. RESULTS The co-existing incidence rate of two diseases was 0.39%. For these concurrent cases, HCC was all at the advanced stage and CE lesions were inactive. Median survival time for HCC patients was 6 month (1-17). However, it was 8 month (3-90) for the co-existing cases and was much longer than the median survival time of HCC patients (P<0.05), which was closely associated with tumor size, location, TMN stage and hydatid size, location, classification. Four of the patients underwent surgical intervention and their median survival time was 17 month (3-68). CONCLUSIONS Echinococcus granulosus may elicit a protective effect against the development and progression of HCC, while more basic and clinical researches are needed.
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Affiliation(s)
- Ran Bo
- Department of Liver Hydatid Disease, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- School of Public Health, Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Aimaiti Yasen
- Department of Liver Hydatid Disease, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- State Key Laboratory on Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Yingmei Shao
- Department of Liver Hydatid Disease, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- Xinjiang Key Laboratory of Echinococcosis, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Wenbao Zhang
- School of Public Health, Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Renyong Lin
- School of Public Health, Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Tiemin Jiang
- Department of Liver Hydatid Disease, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Hao Wen
- Department of Liver Hydatid Disease, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- School of Public Health, Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- Xinjiang Key Laboratory of Echinococcosis, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Hui Xiao
- State Key Laboratory on Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
| | - Tuerganaili Aji
- Department of Liver Hydatid Disease, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
- Xinjiang Key Laboratory of Echinococcosis, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang Uyghur Autonomous Region People’s Republic of China
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17
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Naar L, Hatzaras I, Arkadopoulos N. Management of Cystic Echinococcosis Complications and Dissemination. THE SURGICAL MANAGEMENT OF PARASITIC DISEASES 2020:209-228. [DOI: 10.1007/978-3-030-47948-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Guan W, Zhang X, Wang X, Lu S, Yin J, Zhang J. Employing Parasite Against Cancer: A Lesson From the Canine Tapeworm Echinococcus Granulocus. Front Pharmacol 2019; 10:1137. [PMID: 31607934 PMCID: PMC6774290 DOI: 10.3389/fphar.2019.01137] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 09/03/2019] [Indexed: 01/03/2023] Open
Abstract
Cystic echinococcosis (CE), a devastating zoonotic condition caused by the tapeworm Echinococcus granulosus, remain a significant public health problem worldwide. However, after a negative correlation between solid tumor and CE has been incidentally discovered, accumulating evidence have suggested that this parasite may induce anticancer effect through activating host immune response and secreting molecules with anticancer potential, which may provide some new understanding for immunotherapy. This article will review the evidence supporting the anticancer effect of E. granulosus and its underlying mechanisms and discuss the possible implications in immunotherapy.
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Affiliation(s)
- Wang Guan
- Department of Cancer Prevention and Treatment, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaoqin Zhang
- Intensive Care Unit, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiao Wang
- Department of Cancer Prevention and Treatment, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Shun Lu
- Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jun Yin
- Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jinxin Zhang
- School of Public Health, Sun Yat-sen University, Guangzhou, China
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19
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Jiménez M, Stoore C, Hidalgo C, Corrêa F, Hernández M, Benavides J, Ferreras MC, Sáenz L, Paredes R. Lymphocyte Populations in the Adventitial Layer of Hydatid Cysts in Cattle: Relationship With Cyst Fertility Status and Fasciola Hepatica Co-Infection. Vet Pathol 2019; 57:108-114. [PMID: 31526120 DOI: 10.1177/0300985819875721] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cystic echinococcosis is a worldwide zoonosis caused by the cestode Echinococcus granulosus. Two types of hydatid cysts occur in intermediate hosts: fertile cysts that generate protoscoleces from the germinal layer of the cyst, and infertile cysts that do not produce protoscoleces and are unable to continue the life cycle of the parasite. The adventitial layer, a host-derived fibrous capsule surrounding the hydatid cyst, is suggested to play an important role in local immune regulation during infection and in fertility of the cysts. Fasciola hepatica, another important parasite of cattle, induces a characteristic Th2-like immune response that could modulate the immune response against E. granulosus. Natural co-infection of both parasites is common in cattle, but no reports describe the local immune response against E. granulosus with F. hepatica infection in the same host. This study analyzed the number and distribution of T and B cells in the adventitial layer of liver and lung cysts and the relationship with cyst fertility and F. hepatica co-infection. T lymphocytes were the predominant cell type in the adventitial layer of infertile hydatid cysts and were more numerous in infertile hydatid cysts. B lymphocyte numbers were not associated with hydatid cyst fertility. Mast cells were infrequent in the adventitial layer. The number of T and B cells was not associated with F. hepatica co-infection. The present study contributes to the understanding of local immune responses in bovine cystic echinococcosis.
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Affiliation(s)
- Mauricio Jiménez
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Caroll Stoore
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Christian Hidalgo
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.,Instituto de Ciencias Agronómicas y Veterinarias, Universidad de O'Higgins, Rancagua, Chile
| | - Felipe Corrêa
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.,Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa
| | - Marcela Hernández
- Laboratorio de Biología Periodontal, Facultad de Odontología, Universidad de Chile
| | - J Benavides
- Dpto de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-Universidad de León), Facultad de Veterinaria, Campus de Vegazana s/n, León, Spain
| | - M C Ferreras
- Dpto de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-Universidad de León), Facultad de Veterinaria, Campus de Vegazana s/n, León, Spain
| | - Leonardo Sáenz
- Laboratory of Veterinary Vaccines, Department of Animal Biology, Faculty of Veterinary and Animal Science, Universidad de Chile, Santiago, Chile
| | - Rodolfo Paredes
- Laboratorio de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
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20
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Liao C, Cheng X, Liu M, Wang X, Boireau P. Trichinella spiralis and Tumors: Cause, Coincidence or Treatment? Anticancer Agents Med Chem 2019; 18:1091-1099. [PMID: 29173187 PMCID: PMC6340159 DOI: 10.2174/1871520617666171121115847] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Revised: 10/13/2017] [Accepted: 11/08/2017] [Indexed: 02/07/2023]
Abstract
Background: Conventional therapeutic strategies for tumors have had limited success, and innovative and more effective approaches to treatment are urgently required. The ancient idea that various biological, bacterial, yeast, viral, and para-sitic agents can be used as cancer therapeutics has gradually attracted considerable interest. Certain parasites have been widely discussed in association with human and animal tumors. The purpose of this review was to examine previous literatures which investigates the relations between Trichinella spiralis (T. spiralis) and tumors. Methods: Using PubMed, articles published before 2018 in the whole world have been searched and comprehensively re-viewed. Results: Many researches have provided proofs that T. spiralis possesses antitumor activities. The antitumor effect of T. spi-ralis was first described in the 1970s. However, its research has been inconsistent, and little progress has been made in this field. Therefore, the mechanisms underlying these inhibitory effects are still unclear, and convincing evidence of the links be-tween T. spiralis and the prevention or treatment of tumors from clinical trials is absent. Meanwhile, some other researches al-so suggested that T. spiralis may cause or contribute to coinfection with a tumors. Conclusion: The review has highlighted the scientific literature focussing on evidence for T. spiralis to act as a pro- or anti-tumorigenic agent is summarized and discussed, in hope of contributing to a better understanding of the relations between T. spiralis and tumors
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Affiliation(s)
- Chengshui Liao
- The Key Lab of Animal Disease and Public Health/ College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.,Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.,OIE Collaborating Center for Food-Borne Parasites in the Asian-Pacific Region, Changchun, China
| | - Xiangchao Cheng
- The Key Lab of Animal Disease and Public Health/ College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China
| | - Mingyuan Liu
- Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.,OIE Collaborating Center for Food-Borne Parasites in the Asian-Pacific Region, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Xuelin Wang
- Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.,OIE Collaborating Center for Food-Borne Parasites in the Asian-Pacific Region, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Pascal Boireau
- Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China.,OIE Collaborating Center for Food-Borne Parasites in the Asian-Pacific Region, Changchun, China.,ANSES, Laboratory for Animal Health, Maisons-Alfort, France
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21
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Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang W, McManus DP. Echinococcosis: Advances in the 21st Century. Clin Microbiol Rev 2019; 32:e00075-18. [PMID: 30760475 PMCID: PMC6431127 DOI: 10.1128/cmr.00075-18] [Citation(s) in RCA: 623] [Impact Index Per Article: 103.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Echinococcosis is a zoonosis caused by cestodes of the genus Echinococcus (family Taeniidae). This serious and near-cosmopolitan disease continues to be a significant public health issue, with western China being the area of highest endemicity for both the cystic (CE) and alveolar (AE) forms of echinococcosis. Considerable advances have been made in the 21st century on the genetics, genomics, and molecular epidemiology of the causative parasites, on diagnostic tools, and on treatment techniques and control strategies, including the development and deployment of vaccines. In terms of surgery, new procedures have superseded traditional techniques, and total cystectomy in CE, ex vivo resection with autotransplantation in AE, and percutaneous and perendoscopic procedures in both diseases have improved treatment efficacy and the quality of life of patients. In this review, we summarize recent progress on the biology, epidemiology, diagnosis, management, control, and prevention of CE and AE. Currently there is no alternative drug to albendazole to treat echinococcosis, and new compounds are required urgently. Recently acquired genomic and proteomic information can provide a platform for improving diagnosis and for finding new drug and vaccine targets, with direct impact in the future on the control of echinococcosis, which continues to be a global challenge.
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Affiliation(s)
- Hao Wen
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia and WHO Collaborating Centre for Prevention and Care Management of Echinococcosis, Urumqi, China
| | - Lucine Vuitton
- WHO Collaborating Centre for Prevention and Treatment of Human Echinococcosis and French National Centre for Echinococcosis, University Bourgogne Franche-Comte and University Hospital, Besançon, France
| | - Tuerhongjiang Tuxun
- Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jun Li
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia and WHO Collaborating Centre for Prevention and Care Management of Echinococcosis, Urumqi, China
- Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Dominique A Vuitton
- WHO Collaborating Centre for Prevention and Treatment of Human Echinococcosis and French National Centre for Echinococcosis, University Bourgogne Franche-Comte and University Hospital, Besançon, France
| | - Wenbao Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia and WHO Collaborating Centre for Prevention and Care Management of Echinococcosis, Urumqi, China
- Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Donald P McManus
- Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
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Zarbaliyev E, Hacısalihoğlu P, Sarsenov D. A Rare Case of Pancreatic Tail Hydatid Cyst with Incidental Adenocarcinoma of the Pancreatic Body. Cureus 2019; 11:e3927. [PMID: 30931195 PMCID: PMC6430308 DOI: 10.7759/cureus.3927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Pancreatic hydatid cyst is a rare disease found mostly in endemic regions. Having no specific clinical signs, it may present with tension related abdominal pain, dyspepsia, a palpable mass, and signs of external pressure on the surrounding organs in accordance with localization of the lesion. Pancreatic carcinoma as a neoplastic pathology with poor prognosis can have various clinical presentations changing with localization of the tumor which sometimes has cystic components. Due to the distinct nature of these pathologies, surgical approach can be fairly different. In this report, we present a case of a 70-year-old patient who had an isolated hydatid cyst in the tail of the pancreas with an incidental pancreatic carcinoma in the corpus of the pancreas. The patient was treated with a subtotal pancreatectomy, having no problems in the postoperative period leading to uncomplicated discharge.
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Affiliation(s)
- Elbrus Zarbaliyev
- General Surgery, Istanbul Yeni Yuzyıl University, Gaziosmanpasa Hospital, Istanbul, TUR
| | - Payam Hacısalihoğlu
- Pathology, Istanbul Yeni Yuzyıl University, Gaziosmanpasa Hospital, Istanbul, TUR
| | - Dauren Sarsenov
- General Surgery, Altunizade Acibadem Hospital, Istanbul, TUR
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Ranasinghe SL, McManus DP. Echinococcus granulosus: Cure for Cancer Revisited. Front Med (Lausanne) 2018; 5:60. [PMID: 29594121 PMCID: PMC5857532 DOI: 10.3389/fmed.2018.00060] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 02/19/2018] [Indexed: 12/19/2022] Open
Abstract
Whereas a number of parasites are well recognized risk factors for a number of different cancers in mammalian hosts, there is limited information on the ability of parasitic organisms to induce anticancer effects. There are conflicting reports that echinococcosis, caused by the canine tapeworm Echinococcus granulosus, can decrease or increase cancer risk. This review considers both indirect anticancer effects as the result of adaptive immunity generated against certain echinococcal antigens and the direct effect of molecules released by E. granulosus whose activity directly inhibits cancer cell migration and growth. In conclusion, E. granulosus probably secretes molecules that can be developed as anticancer therapeutics in future.
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Affiliation(s)
- Shiwanthi L Ranasinghe
- Molecular Parasitology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Donald P McManus
- Molecular Parasitology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
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24
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25
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Sevmis M, Yoyen-Ermis D, Aydin C, Bilgic E, Korkusuz P, Uner A, Hamaloglu E, Esendagli G, Karakoc D. Splenectomy-Induced Leukocytosis Promotes Intratumoral Accumulation of Myeloid-Derived Suppressor Cells, Angiogenesis and Metastasis. Immunol Invest 2017; 46:663-676. [DOI: 10.1080/08820139.2017.1360339] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Murat Sevmis
- Department of General Surgery, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Digdem Yoyen-Ermis
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
| | - Cisel Aydin
- Department of Pathology, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Elif Bilgic
- Department of Histology and Embryology, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Petek Korkusuz
- Department of Histology and Embryology, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Aysegul Uner
- Department of Pathology, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Erhan Hamaloglu
- Department of General Surgery, Medical Faculty, Hacettepe University, Ankara, Turkey
| | - Gunes Esendagli
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
| | - Derya Karakoc
- Department of General Surgery, Medical Faculty, Hacettepe University, Ankara, Turkey
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26
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Oikonomopoulou K, Yu H, Wang Z, Vasiliou SK, Brinc D, Christofi G, Theodorou M, Pavlou P, Hadjisavvas A, Demetriou CA, Kyriacou K, Diamandis EP. Association between Echinococcus granulosus infection and cancer risk - a pilot study in Cyprus. Clin Chem Lab Med 2017; 54:1955-1961. [PMID: 27327131 DOI: 10.1515/cclm-2016-0125] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 05/03/2016] [Indexed: 01/06/2023]
Abstract
BACKGROUND Infections from microorganisms and parasites have been connected with either increased or decreased cancer risk. The objective of this study was to investigate whether infection by Echinococcus granulosus is associated with cancer risk. METHODS We assembled a pilot retrospective cohort of patients who were diagnosed as being infected by E. granulosus in Cyprus between 1930 and 2011. Age/gender-matched non-infected family members and neighbors were selected as references. Medical history was ascertained from each study subject through in-person interview. Cox proportional hazards regression analysis was performed to assess the association of being infected by E. granulosus with cancer risk. RESULTS Individuals with prior infection by E. granulosus (n=249) were more likely to have cancer compared to those without infection (n=753), 11.65% vs. 8.37% (p=0.0492). Survival analysis also showed that subjects with prior infection had a higher risk for developing cancer. The hazards ratio (HR) was 1.595, [95% confidence interval (CI) between 1.008 and 2.525]. The risk ratio did not change significantly (HR=1.536; 95% CI: 0.965-2.445) after adjusting for gender, year of birth, smoking status, alcohol consumption, and family history of cancer. CONCLUSIONS Our study suggests that infection by E. granulosus may increase cancer risk. If this observation can be confirmed independently, further investigation of the mechanisms underlying the association is warranted.
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27
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Kern P, Menezes da Silva A, Akhan O, Müllhaupt B, Vizcaychipi KA, Budke C, Vuitton DA. The Echinococcoses: Diagnosis, Clinical Management and Burden of Disease. ADVANCES IN PARASITOLOGY 2017; 96:259-369. [PMID: 28212790 DOI: 10.1016/bs.apar.2016.09.006] [Citation(s) in RCA: 321] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The echinococcoses are chronic, parasitic diseases that are acquired after ingestion of infective taeniid tapeworm eggs from certain species of the genus Echinococcus. Cystic echinococcosis (CE) occurs worldwide, whereas, alveolar echinococcosis (AE) is restricted to the northern hemisphere, and neotropical echinococcosis (NE) has only been identified in Central and South America. Clinical manifestations and disease courses vary profoundly for the different species of Echinococcus. CE presents as small to large cysts, and has commonly been referred to as 'hydatid disease', or 'hydatidosis'. A structured stage-specific approach to CE management, based on the World Health Organization (WHO) ultrasound classification of liver cysts, is now recommended. Management options include percutaneous sterilization techniques, surgery, drug treatment, a 'watch-and-wait' approach or combinations thereof. In contrast, clinical manifestations associated with AE resemble those of a 'malignant', silently-progressing liver disease, with local tissue infiltration and metastases. Structured care is important for AE management and includes WHO staging, drug therapy and long-term follow-up for at least a decade. NE presents as polycystic or unicystic disease. Clinical characteristics resemble those of AE, and management needs to be structured accordingly. However, to date, only a few hundreds of cases have been reported in the literature. The echinococcoses are often expensive and complicated to treat, and prospective clinical studies are needed to better inform case management decisions.
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Affiliation(s)
- P Kern
- University Hospital of Ulm, Ulm, Germany
| | | | - O Akhan
- Hacettepe University, Ankara, Turkey
| | - B Müllhaupt
- University Hospital of Zurich, Zürich, Switzerland
| | - K A Vizcaychipi
- National Institute of Infectious Diseases, Buenos Aires, Argentina
| | - C Budke
- Texas A&M University, College Station, TX, United States
| | - D A Vuitton
- Université de Franche-Comté, Besançon, France
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28
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Peón AN, Ledesma-Soto Y, Terrazas LI. Regulation of immunity by Taeniids: lessons from animal models and in vitro studies. Parasite Immunol 2016; 38:124-35. [PMID: 26457989 DOI: 10.1111/pim.12289] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 10/01/2015] [Indexed: 02/06/2023]
Abstract
Taeniidae is the largest family of the Cyclophyllidea order of parasites despite being composed of just two genera: Taenia spp and Echinococcus spp. These parasites are flatworms with a terrestrial life cycle, having an immature or larval stage called metacestode, which develops into the mature form within the intestine of the primary host after being consumed in raw or poorly cooked meat. Consumed eggs hatch into oncospheres, penetrate the intestinal walls and are transported via the bloodstream to later develop into metacestodes within the muscles and internal organs of secondary and sometimes primary hosts, thereby initiating the cycle again. Larval stages of both Taenia spp and Echinococcus spp are well known to produce tissue-dwelling, long-lasting infections; in this stage, these parasites can reach centimetres (macroparasites) and both genera may cause life-threatening diseases in humans. Establishing such long-term infections requires an exceptional ability to modulate host immunity for long periods of time. In this review, we analyse the immunoregulatory mechanisms induced by these tapeworms and their products, mainly discussing the importance of taeniid strategies to successfully colonize their hosts, such as antigen-presenting cell phenotype manipulation and the consequent induction of T-cell anergy, among others.
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Affiliation(s)
- A N Peón
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, México
| | - Y Ledesma-Soto
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, México
| | - L I Terrazas
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, México
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29
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Díaz A, Casaravilla C, Barrios AA, Ferreira AM. Parasite molecules and host responses in cystic echinococcosis. Parasite Immunol 2016; 38:193-205. [PMID: 26425838 DOI: 10.1111/pim.12282] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 09/22/2015] [Indexed: 01/03/2023]
Abstract
Cystic echinococcosis is the infection by the larvae of cestode parasites belonging to the Echinococcus granulosus sensu lato species complex. Local host responses are strikingly subdued in relation to the size and persistence of these larvae, which develop within mammalian organs as 'hydatid cysts' measuring up to tens of cm in diameter. In a context in which helminth-derived immune-suppressive, as well as Th2-inducing, molecules garner much interest, knowledge on the interactions between E. granulosus molecules and the immune system lags behind. Here, we discuss what is known and what are the open questions on E. granulosus molecules and structures interacting with the innate and adaptive immune systems, potentially or in demonstrated form. We attempt a global biological approach on molecules that have been given consideration primarily as protective (Eg95) or diagnostic antigens (antigen B, antigen 5). We integrate glycobiological information, which traverses the discussions on antigen 5, the mucin-based protective laminated layer and immunologically active preparations from protoscoleces. We also highlight some less well-known molecules that appear as promising candidates to possess immune-regulatory activities. Finally, we point out gaps in the molecular-level knowledge of this infectious agent that hinder our understanding of its immunology.
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Affiliation(s)
- A Díaz
- Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) and Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay
| | - C Casaravilla
- Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) and Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay
| | - A A Barrios
- Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) and Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay
| | - A M Ferreira
- Cátedra de Inmunología, Departamento de Biociencias (Facultad de Química) and Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay
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Kursunel MA, Esendagli G. The untold story of IFN-γ in cancer biology. Cytokine Growth Factor Rev 2016; 31:73-81. [DOI: 10.1016/j.cytogfr.2016.07.005] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 07/07/2016] [Accepted: 07/07/2016] [Indexed: 12/21/2022]
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31
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Puzzling and ambivalent roles of malarial infections in cancer development and progression. Parasitology 2016; 143:1811-1823. [DOI: 10.1017/s0031182016001591] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
SUMMARYScientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth.Plasmodiumprotozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans,Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.
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Golubnitschaja O, Yeghiazaryan K, Stricker H, Trog D, Schild HH, Berliner L. Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours. BMC Cancer 2016; 16:357. [PMID: 27277077 PMCID: PMC4898377 DOI: 10.1186/s12885-016-2382-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 05/24/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. METHODS A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium(90) or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). RESULTS Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. CONCLUSIONS It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced metastatic disease of breast cancer be undertaken, with an appropriate patients' stratification, set-up of the relevant patient profiles and disease modelling.
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Affiliation(s)
- Olga Golubnitschaja
- Department of Radiology, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany.
| | - Kristina Yeghiazaryan
- Department of Radiology, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
| | - Helena Stricker
- Department of Radiology, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
| | | | - Hans H Schild
- Department of Radiology, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
| | - Leonard Berliner
- New York Methodist Hospital, NY Presbyterian Healthcare System, Brooklyn, NY, USA
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Abstract
The World Health Organization lists a constellation of 17 tropical diseases that afflict approximately one in six individuals on the planet and, until recently, few resources have been devoted to the treatment and eradication of those diseases. They are often referred to as the diseases of the “bottom billion,” because they are most prevalent among the poorest individuals in impoverished tropical nations. However, the few studies that have been performed reveal an extraordinary world of molecular and cellular adaptations that facilitate the pathogens’ survival in hosts ranging from insects to humans. A compelling case can be made that even a modest investment toward understanding the basic molecular and cell biology of these neglected pathogens has a high probability of yielding exciting new cellular mechanisms and insights into novel ways of combating these diseases.
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Affiliation(s)
- William Sullivan
- Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064
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34
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Machicado C, Marcos LA. Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review. Int J Cancer 2016; 138:2915-21. [DOI: 10.1002/ijc.30028] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 12/08/2015] [Accepted: 01/25/2016] [Indexed: 11/08/2022]
Affiliation(s)
- Claudia Machicado
- Research Scientist, Bioinformatics Laboratory, Department of Cellular and Molecular Sciences, School of Sciences and Philosophy; Universidad Peruana Cayetano Heredia; Av Honorio Delgado 430, Urb. Ingeniería Lima 31 Peru
- Institute for Biocomputation and Physics of Complex Systems; University of Zaragoza, Spain; Mariano Esquillor, Edificio I + D Zaragoza 50018 Spain
| | - Luis A. Marcos
- Department of Medicine; Stony Brook University; Stony Brook NY
- Instituto De Medicina Tropical Alexander Von Humboldt; Universidad Peruana Cayetano Heredia; Lima Peru
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35
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Tez S, Tez M. Echinococcus and cancer: unsolved mystery. Parasite Immunol 2015; 37:426. [PMID: 26216021 DOI: 10.1111/pim.12201] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 04/10/2015] [Indexed: 11/30/2022]
Affiliation(s)
- S Tez
- Department of Radiology, 19 Mayis Hospital, Dikmen, Ankara, Turkey
| | - M Tez
- Surgery Clinic, Numune Training and Research Hospital, Sıhhiye, Ankara, Turkey
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36
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Esendagli G, Abbasoglu O. Immune system in cancer and hydatid disease: cross‐reactivity vs. immune modulation. Parasite Immunol 2015; 37:427-428. [DOI: 10.1111/pim.12200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- G. Esendagli
- Department of Basic Oncology Hacettepe University Cancer Institute Ankara Turkey
| | - O. Abbasoglu
- Department of General Surgery Medical Faculty, Hacettepe University Ankara Turkey
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