Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells and result in oxidative and nitrative DNA damage, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in the initiation and/or promotion of inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including parasites (Schistosoma haematobium(SH) andOpisthorchis viverrini(OV)), viruses (hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV)), and bacteriumHelicobacter pylori(HP). SH, OV, HCV, HPV, EBV, and HP are important risk factors for bladder cancer, cholangiocarcinoma, hepatocellular carcinoma, cervical cancer, nasopharyngeal carcinoma, and gastric cancer, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS) expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that oxidative and nitrative DNA damage in stem cells may play a key role in inflammation-related carcinogenesis.

Praziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis.

The present study was designed to identify the chemical constituents of the methanolic extract of Curcuma longa L. rhizomes and their inhibitory effect on a hepatoma cell line. The methanolic extract was subjected to GC-MS analysis to identify the volatile constituents and the other part of the same extract was subjected to liquid column chromatographic separation to isolate curcumin. The inhibition of cell growth in the hepatoma cell line and the cytopathological changes were studied. GC-MS analysis showed the presence of fifty compounds in the methanolic extract of C. longa. The major compounds were ar-turmerone (20.50 %), β-sesquiphellandrene (5.20 %) and curcumenol (5.11 %). Curcumin was identified using IR, ¹H and ¹³C NMR. The inhibition of cell growth by curcumin (IC₅₀ = 41.69 ± 2.87 μg mL^-1) was much more effective than that of methanolic extract (IC₅₀ = 196.12 ± 5.25 μg mL^-1). Degenerative and apoptotic changes were more evident in curcumin- treated hepatoma cells than in those treated with the methanol extract. Antitumor potential of the methanolic extract may be attributed to the presence of sesquiterpenes and phenolic constituents including curcumin (0.051 %, 511.39 μg g^-1 dried methanol extract) in C. longa rhizomes.

Inflammation may activate stem cells via prostaglandin E2 (PGE2) production mediated by cyclooxygenase-2 (COX-2) expression. We performed an immunohistochemical analysis of the expression of stemness markers (Oct3/4 and CD44v6) and COX-2 in urinary bladder tissues obtained from cystitis and cancer patients with and withoutSchistosoma haematobiuminfections. Immunoreactivity to Oct3/4 was significantly higher inS. haematobium-associated cystitis and cancer tissues than in normal tissues. CD44v6 expression was significantly higher in bladder cancer withoutS. haematobiumthan in normal tissues. COX-2 was located in the cytoplasmic membrane, cytoplasm, and nucleus of the cancer cells. Interestingly, the nuclear localization of COX-2, which was reported to function as a transcription factor, was significantly associated with the upregulation of Oct3/4 and CD44v6 in bladder cancer tissues with and withoutS. haematobiuminfection, respectively. COX-2 activation may be involved in inflammation-mediated stem cell proliferation/differentiation in urinary bladder carcinogenesis.