Development of Cryptosporidium parvum-Induced Gastrointestinal Neoplasia in Severe Combined Immunodeficiency (SCID) Mice: Severity of Lesions Is Correlated with Infection Intensity

Abstract

Abstract. We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium -induced cell transformation, SCID mice treated with dexamethasone were challenged with C. parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (10 6 -10 7

Fulminant Cryptosporidiosis after Near-Drowning: a Human Cryptosporidium parvum Strain Implicated in Invasive Gastrointestinal Adenocarcinoma and Cholangiocarcinoma in an Experimental Model

“…Additionally, the results of this study showed for the first time the ability of an isolate of C. parvum of human origin to cause gastrointestinal and biliary adenocarcinomas in an experimental model, providing supplementary evidence of a direct role of this parasite in the induction of digestive cancer (4)(5)(6). Furthermore, these findings demonstrate that C. parvum-induced neoplasia is an invasive process that can evolve rapidly in immunosuppressed hosts.…”

“…However, in this report it was unclear whether C. parvum behaved as a carcinogenesis factor or simply as an opportunistic agent whose development was enhanced by host immunosuppression. More consistent with a potential tumorigenic role of this parasite, we recently showed that IOWA and TUM1 strains of C. parvum of animal origin induced digestive neoplasia in a rodent model (4)(5)(6). We report herein the first evidence of the ability of a human-derived C. parvum strain to induce gastrointestinal cancer in mice.…”

“…On the other hand, the extremely high parasite shedding in this patient allowed us to purify a large amount of infective oocysts from stools and to infect SCID mice to test the tumorigenic potential of a human-derived C. parvum isolate. We recently showed that C. parvum strains of animal origin induce digestive cancer in SCID mice (4)(5)(6).…”

“…Oocyst viability was assessed by testing excystation (5,6), and the infectivity of parasites was verified by a preliminary oral inoculation of four SCID mice. These animals developed C. parvum infection and were followed throughout the experiment.…”

“…Parasite load in digestive sections was scored as follows: 0, no parasites; ϩ1, small number of parasites, focally distributed; ϩ2, moderate number of parasites, widely distributed; and ϩ3, abundant parasites present, widely distributed throughout the section (4,5). Lesions at different sites were scored as described previously (4,5), with slight modifications as follows: 0, no lesion; 1, inflammation and/or regenerative changes; 2, low-grade intraepithelial neoplasia (LGIEN); 3, high-grade intraepithelial neoplasia (HGIEN); 4, suspicion of invasive adenocarcinoma or invasive adenocarcinoma (penetration of dysplastic glands through the muscularis mucosae with desmoplastic stromal response); and 5, adenocarcinoma with the invasion through the submucosa and deeper. (Note that in category 3, adenoma with HGIEN, carcinoma in situ [limited to the epithelium], and intramucosal adenocarcinoma [invasion of the lamina propria] were also included.…”