In our experimental model, bone marrow-derived mesenchymal stem cells injection improved muscle regeneration and increased contractile function of anal sphincters after injury and repair. Therefore, mesenchymal stem cells may represent an attractive tool for treating anal sphincter lesions in humans. Investigations into the biologic basis of this phenomenon should increase our knowledge on underlying mechanisms involved in sphincter repair.

Background/Aims-Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with diVerent cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation. Methods-Well separated H pylori colonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined for cagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients' sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically. Results-Of the 747 colonies examined, 45.3% were cagA+. All colonies from four patients were cagA+, and all colonies from two patients were cagA−. In 13 patients (68%) both cagA+ and cagA− colonies were found. CagA expression of isolates corresponded to their cagA status. H pylori strains with diVerent CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p< 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites. Conclusions-Most patients with nonulcer dyspepsia are infected by both cagA+ and cagA− H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia. (Gut 1998;42:772-778)

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro , to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites.

The aim of this study was to investigate the relationship between preoperative serum ferritin levels, clinicopathological parameters and survival analysis of patients with colorectal cancer. Ninety-four patients (57 males) with a mean age of 65 years (39-87 years) underwent 63 curative and 31 palliative operations. Follow-up was at least 5 years. Patients were categorized with normal (30-215 ng/mL in men and 11-148 ng/mL in women), low, or high serum ferritin levels. Prognostic evaluation was undertaken with stratified survival analysis and Cox's regression model. Twenty-nine of the patients (30.9%) had raised ferritin levels and 14 (14.9%) had low values. Comparisons of the survival curves showed significant differences in stage C disease; specifically, patients with either low or high ferritin levels had a shorter survival than patients with normal levels. Patients who underwent palliative surgery and had high ferritin serum values also had a shorter survival. In multivariate analysis, the variables with a negative effect on survival were stage, serum ferritin levels and age. Our data suggest that patients with advanced colorectal cancer having normal preoperative serum ferritin levels may have a better prognosis, although the prognostic value related to this association requires further investigation.