Table 2.

a and b: in vitro and in vivo studies of the anti-neoplastic activity of different parasites against hepato-pancreatic cancers (hepatocellular carcinoma and pancreatic cancer)

a. Hepatocellular carcinoma
Parasite	Type of study	Antineoplastic activity	References
Schistosoma japonicum
S. japonicum Sja-miRNA-7-5p	In vitro and in vivo	Significantly inhibited the migration of mouse and human hepatoma cells and significantly inhibited tumor growth in a xenograft animal model through down-regulation of the S-phase kinase-associated protein 2 gene	[111]
S. japonicum Sja-miR-3096	In vitro and in vivo	Significantly inhibited the migration of both murine and human hepatoma cell lines and significantly inhibited tumor growth in the murine model by targeting phosphoinositide 3-kinase class II alpha (PIK3C2A)	[112]
S. japonicum Sja-miR-61	In vitro and in vivo	Significantly inhibited the migration of both mouse and human hepatoma cells and significantly inhibited tumor growth in the murine model through anti-angiogenesis activity by targeting the PGAM1 gene	[113]
S. japonicum Sja-miR-71a	In vitro and in vivo	Significantly inhibited the migration of both mouse and human hepatoma and human HCC cell lines and significantly inhibited tumor growth in a xenograft mouse model by targeting the FZD4 gene	[114]
Fasciola hepatica
F. hepatica (biologically active substances)	In vitro	Significant inhibitory effect on MC29 hepatoma cell line proliferation	[116]
Trichinella spiralis
T. spiralis crude antigens (mixture from adult and newborn larvae)	In vitro	Apoptosis of ascitic hepatoma (cell line H22), and hepatoma cell line (H7402)	[104]
T. spiralis Excretory secretory products (ESP) from adult worms or muscle larvae	In vitro	Inhibited cellular proliferation and induced apoptosis in liver cancer (H22) cells through the mitochondrial pathway	[117]
T. spiralis infection	In vivo	Significantly inhibited mouse ascitic hepatoma H22 in ICR mice	[117]
T. spiralis protein encoded by the A200711 gene	In vitro	Induced apoptosis in human hepatoma H7402 cells	[118]
T. spiralis larval extract (peptide2 matched the hypothetical protein T01_4238 of T. spiralis)	In vitro	Inhibition of proliferation of HepG2 cells in a dose-dependent manner	[119]
T. spiralis infection	In vivo	Significantly inhibited hepatoma Hep1-6 carcinoma growth in the C57BL/6 mice	[120]
T. spiralis infection	In vivo	Decreased progression of the tumor with increased rate of apoptosis as shown by the decreased expression of Bcl-2 and increased rat survival time	[121]
Angiostrongylus cantonensis
A. cantonensis, excretory–secretory products (ESPs) and recombinant Calreticulin (rCRT) (a key effector protein of ESPs)	In vitro	Both induced apoptosis in human hepatoma HepG2 cells. rCRT had a stronger inhibitory effect on HepG2 cells compared to ESPs	[123]
A. cantonensis, excretory–secretory products (ESPs)	In vivo	Significantly reduced tumor growth in Hepa1-6 mouse tumor model	[123]
Setaria equina
S. equina excretory–secretory products (SeES) alone and in combination with diethylcarbamazine citrate (DEC)	In vivo	Had a beneficial effect on HCC development in the rat model by increasing the activity of antioxidant enzymes and decreasing the expression of NF κB. Combination with DEC modulates the antioxidant effect of SeES and induces immunomodulatory and protective effects on rat HCC	[124, 125]
Rabbit anti-S. equina extract and diethylcarbamazine citrate polyclonal IgG antibodies	Indirect ELISA and Western blotting	Cross-reactive protein bands in S. equina and Huh-7 hepatoma cells at 75 and 70 kDa by anti-S. equina and anti-diethylcarbamazine antibodies, respectively	[126]
Plasmodium spp.
P. berghei infection	In vivo	Reduced hepatic carcinoma development induced by aflatoxin B1 in rats	[128]
P. yoelii 17 XNL infection	In vivo	Significantly inhibited tumor progression in murine implanted hepatoma model and prolonged their survival time through suppression of angiogenesis within the tumor microenvironment	[129]
Plasmodium-based vector (P.y-GPC3) P. yoelii 17XNL expressing murine glypican-3 protein (expressed in Hepa1-6 cells)	In vivo	Significantly inhibited Hepa1-6-induced tumor growth in the implanted HCC murine model, prolonged their survival time, and induced tumor antigen-specific T-cell-mediated immunity	[131]
P. yoelii infection	In vivo	Significantly inhibited the recurrence and metastasis and improved the prognosis of HCC in both non-resection and resection murine orthotopic HCC models	[132]
Toxoplasma gondii
T. gondii tachyzoites RH strain	In vitro	Inhibited the proliferation and induced apoptosis of HCC (H7402) cells in a concentration-dependent manner	[133]
GRA16, a dense granule protein of T. gondii	In vitro and in vivo	Decreased cell proliferation, anti-apoptotic factors, p‐AKT/AKT ratio, cell migration, and invasive activity of hepatocellular carcinoma (HepG2) cells and decreased tumor size in HepG2 cell‐xenograft nude mice	[134]
T. gondii GRA15II-polarized macrophages	In vitro and in vivo	Significantly inhibited migration and invasion of the Hepa1-6 cells and markedly restricted tumor growth in tumor-bearing C57BL/6 mice	[135]

b. Pancreatic cancer
Parasite	Type of study	Antineoplastic activity	References
Echinococcus granulosus
E. granulosus live protoscolex to induce secondary hydatidosis	In vivo	Significantly inhibited the development of precursor foci of neoplastic changes in the pancreas in the azaserine-rat model	[138]
Toxoplasma gondii
A live, non-replicating avirulent uracil auxotroph vaccine strain (cps) of T. gondii	In vivo	Significantly regressed established tumor in pancreatic ductal adenocarcinoma mouse model	[139]
A live, non-replicating avirulent uracil auxotroph vaccine strain (cps) of T. gondii	In vivo	Induced significant therapeutic benefit through generating anti-tumor immune responses in established aggressive disseminated pancreatic cancer in a mouse model	[140]
A live, non-replicating avirulent uracil auxotroph vaccine strain (cps) of T. gondii	In vivo	Stimulated long-term strong immune protection against the recurrence of pancreatic cancer in mice that survived the primary pancreatic tumor after cps treatment	[141]
Attenuated Toxoplasma NRTUA strain and combination therapy with anti-PD-1 antibody	In vivo	Monotherapy with attenuated Toxoplasma NRTUA inhibited tumor growth in a mouse model of PDAC and its combination with anti-PD1 antibody enhanced its anti-tumor activity and controlled tumor growth in Pan02 tumor-bearing mice	[142]
T. gondii soluble antigen and T. gondii profilin	In vivo	Significantly decreased tumor volume and increased tumor infiltration with CD4+ and CD8+ T cells	[143]