Anti-Anisakis antibodies in colon cancer patients and their relationship with γδ T-cells.

Many pathogens are related to carcinogenesis. Chronic inflammation, as a result of persistent infection, leads to DNA damage, higher expression of oncogenes, decreased apoptosis and immunosuppression, which are some of the reasons for cancer induction. Among parasites, Schistosoma, Opistorchis and Clonorchis are recognised as infectious agents which contribute to cancer. A relationship between Anisakis and cancer was hypothesised because cellular responses to Anisakis products could result in inflammation and DNA damage. Previous research has shown a decrease in CD8+ γδ T-cells and an increase in αß and γδ T-cell apoptosis in colon cancer (CC) samples. Ninety-two CC patients and 60 healthy subjects were recruited. γδ and αß T-cells were analysed, and their apoptosis was evaluated. Anti-Anisakis antibodies were tested in sera from CC patients and controls. Anti-Anisakis IgG, IgM, IgA and IgE antibodies were significantly higher in CC patients. A significant increase in anti-Anisakis IgA levels was observed in patients with angiolymphatic invasion. The number of all γδ T-cells, as well as CD3+ CD4+ αß T-cells, was significantly lower in CC patients. The apoptosis of all T-cells was significantly increased in patients with CC. We observed a significantly higher percentage of anti-Anisakis IgE positive patients having a deficit of CD3+ γδ T-cells. Our results suggest a relationship between Anisakis and CC.

Three-dimensional (3D) culture of adult murine colon as an in vitro model of cryptosporidiosis: Proof of concept.

Cryptosporidium parvum is a major cause of diarrheal illness and was recently potentially associated with digestive carcinogenesis. Despite its impact on human health, Cryptosporidium pathogenesis remains poorly known, mainly due to the lack of a long-term culture method for this parasite. Thus, the aim of the present study was to develop a three-dimensional (3D) culture model from adult murine colon allowing biological investigations of the host-parasite interactions in an in vivo-like environment and, in particular, the development of parasite-induced neoplasia. Colonic explants were cultured and preserved ex vivo for 35 days and co-culturing was performed with C. parvum. Strikingly, the resulting system allowed the reproduction of neoplastic lesions in vitro at 27 days post-infection (PI), providing new evidence of the role of the parasite in the induction of carcinogenesis. This promising model could facilitate the study of host-pathogen interactions and the investigation of the process involved in Cryptosporidium-induced cell transformation.

High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients.

BACKGROUND: The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients. METHODOLOGY AND PRINCIPAL FINDINGS: Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65-9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44-89.02, P = 0.003). CONCLUSIONS: This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease.

Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer.

Dysfunctions at human intestinal barrier by water-borne protozoan parasites: lessons from cultured human fully differentiated colon cancer cell lines.

Some water-borne protozoan parasites induce diseases through their membrane-associated functional structures and virulence factors that hijack the host cellular molecules and signalling pathways leading to structural and functional lesions in the intestinal barrier. In this Microreview we analyse the insights on the mechanisms of pathogenesis of Entamoeba intestinalis, Giardia and Cryptosporidium observed in the human colon carcinoma fully differentiated colon cancer cell lines, cell subpopulations and clones expressing the structural and functional characteristics of highly specialized fully differentiated epithelial cells lining the intestinal epithelium and mimicking structurally and functionally an intestinal barrier.

Anisakidosis of the sigmoid colon disguising as metastatic carcinoma: a case report and review of the literature.

Intestinal anisakidosis is a rare nematode infestation caused by the ingestion of larvae-infected raw or undercooked fish. Most cases are incidentally diagnosed during surgery for other reasons. We present such a case of anisakid larvae seen in a patient's sigmoid colon resected for adenocarcinoma, where a subserosal nodule caused by the inflammatory reaction to the worm was presumed to be a lymph node involved by metastatic tumor. With the increasing popularity of raw fish consumption, the incidence of this parasitic infection is bound to increase, requiring surgical pathologists to be cognizant of its existence and aware of its histologic appearance.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients.

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Proximal tumors are associated with greater mortality in colon cancer.

BACKGROUND: Colon cancer is the third leading cause of death from cancer in the United States. Recent studies report on increasing proportions of proximal cancers. The etiology behind this epidemiological trend is unclear, and its implication on survival outcomes is unknown. Further analysis of the impact of anatomic site of disease among a large multiethnic population will help facilitate research and education to improve colon cancer screening and treatment. OBJECTIVE: To investigate the association between proximal tumor location and survival in patients with colon cancer. DESIGN AND PARTICIPANTS: A large retrospective cohort study in the US utilizing the Surveillance, Epidemiology, and End Results (SEER) cancer registry analyzed survival outcomes of patients with colon cancer. Multivariable logistic regression analyses investigated sex-specific, race/ethnicity-specific, and anatomic site-specific disparities in survival. MAIN MEASURES: Five-year survival outcomes from colon cancer. RESULTS: Our study demonstrated significant disparities in survival by sex, race/ethnicity, and anatomic site. Across all time periods and among most cohorts, patients with proximal cancers had significantly worse survival outcomes. When compared to distal cancers, patients with proximal cancers were 13% less likely to survive 5 years (OR 0.87; 95% CI, 0.82-0.91). When compared to non-Hispanic whites, blacks were 30% less likely to survive 5 years (OR 0.70; 95% CI, 0.68-0.73). Stage-specific multivariable regression analysis of localized cancers demonstrated similar findings. CONCLUSIONS: Significant race-specific, sex-specific, and anatomic site-specific disparities in colon cancer survival exist. Proximal cancers are associated with worse survival odds. These disparities may reflect differences in the genotype and phenotype of colon cancer among these groups. A modified risk assessment tool that incorporates these variations may be more effective in the early detection and treatment of colon cancer.

Intestinal protozoa are hypothesized to stimulate immunosurveillance against colon cancer.

Colon cancer in humans results in considerable morbidity and mortality throughout most of the world. During the twentieth century, there was a rapid rise in colon cancer within modernizing countries that has not been adequately explained, although the role of diet has been widely explored. Previously, we showed that the presence of the endemic Eimeria spp. protozoan in intestinal tissues is associated with regions of low tumorigenesis in the large and small bovine intestine and that an Eimeria surface protein is a potent activator of dendritic cells and a useful immunomodulator, with anti-cancer and anti-viral properties. Therefore, we hypothesize that the persistent presence of such an intestinal protozoan enhances immunosurveillance by elevating the intestinal alert status and that the loss of these organisms could lead to a higher incidence of colon cancer. Preliminary support of this hypothesis derives from the observations that domestic animals, known to maintain this protozoan, have very low colon cancer incidence. We propose that this also may occur in human populations that use human excrement (night soil) as a fertilizer, a practice that serves to complete the life cycle of this type of microbe. We examine some evidence for this hypothesis in Japan's mortality patterns, where we show that colon cancer increased after the cessation of night soil use, but before the change to a western diet. We conclude that this hypothesis, a variation of the hygiene hypothesis, is worth further consideration and continued elaboration.

Cryptosporidium parvum at different developmental stages modulates host cell apoptosis in vitro.

We studied apoptosis in a human ileocecal adenocarcinoma tumor cell line (HCT-8) infected with Cryptosporidium parvum, from 2 to 72 h postinfection (h.p.i.). At 2 h.p.i., the percentage of annexin V-positive cells in the cell culture had increased to 10% compared to 2.5% in noninfected control culture; sorted infected cells expressed mRNA of FasL, the active form of caspase 3, and high caspase 3 activity, whereas the noninfected neighboring cells sorted from the same culture showed no signs of apoptosis. At 24 h.p.i., the percentages of early (annexin V positive) and late (DNA fragment) apoptotic cells were 13 and 2%, respectively, in the entire cell culture, and these percentages were not statistically significant in comparison with those from noninfected control cultures. At this time, sorted infected cells expressed the inactive form of caspase 3, a low caspase 3 activity, and the antiapoptotic protein Bcl-2. Noninfected cells sorted from the same culture showed expression of the active form of caspase 3, a moderate caspase 3 activity, and no Bcl-2 expression. At 48 h.p.i., the percentages of early and late apoptotic cells and caspase 3 activity had increased in the total cell culture, and both sorted infected and noninfected cells showed the active form of caspase 3. These results show that C. parvum, depending on its developmental stage, can inhibit (at the trophozoite stage) or promote (at the sporozoite and merozoite stages) host cell apoptosis, suggesting that it is able to interact with and regulate the host-cell gene expression.

[Two cases of parasitic granuloma found incidentally in surgical specimens].

Occasionally, parasitosis demonstrates no clinical symptoms, and is found incidentally. We report 2 cases of parasitic granuloma found incidentally in surgical specimens in rare sites for parasitosis. Case 1 was a 40-year-old female. She was diagnosed with inguinal hernia, and operation was performed. A white nodule, measured 1.5 x 1 x 1 cm in size, was found in the hernia sac. The nodule was elastic hard and solid. Histologically, eosinophilic granuloma was demonstrated, and the parasite was characterized by renette cell and Y-shaped lateral cord, and suggesting extra-gastrointestinal anisakiasis. Case 2 was a 71-year-old female. She was diagnosed with colonic adenocarcinoma, and colectomy was performed. A white nodule, measured 1 x 1 x 0.8 cm in size was found in the omentum, at first identified as peritoneal dissemination of colonic carcinoma. However, histological findings of the nodule showed eosinophilic granuloma, and parasite was observed in the granuloma. The parasite was characterized by thick cuticle and muscular cells, and suggestive of dilofilariasis. In each case, no clinical symptoms of parasitosis were recognized, and each lesion presented in a rare site as anisakiasis or dirofilariasis. When any lesions as in the present cases is found in a surgical specimen, it is important to make differential diagnosis with consideration for parasitic granuloma.