Mannan binding lectin-associated serine protease 1 is induced by hepatitis C virus infection and activates human hepatic stellate cells.

Mannan binding lectin (MBL)-associated serine protease type 1 (MASP-1) has a central role in the lectin pathway of complement activation and is required for the formation of C3 convertase. The activity of MASP-1 in the peripheral blood has been identified previously as a highly significant predictor of the severity of liver fibrosis in hepatitis C virus (HCV) infection, but not in liver disease of other aetiologies. In this study we tested the hypotheses that expression of MASP-1 may promote disease progression in HCV disease by direct activation of hepatic stellate cells (HSCs) and may additionally be up-regulated by HCV. In order to do so, we utilized a model for the maintenance of primary human HSC in the quiescent state by culture on basement membrane substrate prior to stimulation. In comparison to controls, recombinant MASP-1 stimulated quiescent human HSCs to differentiate to the activated state as assessed by both morphology and up-regulation of HSC activation markers α-smooth muscle actin and tissue inhibitor of metalloproteinase 1. Further, the expression of MASP-1 was up-regulated significantly by HCV infection in hepatocyte cell lines. These observations suggest a new role for MASP-1 and provide a possible mechanistic link between high levels of MASP-1 and the severity of disease in HCV infection. Taken together with previous clinical observations, our new findings suggest that the balance of MASP-1 activity may be proinflammatory and act to accelerate fibrosis progression in HCV liver disease.

Primary adenocarcinoma in an ileostomy: a late complication of surgery for ulcerative colitis.

In the 1950s the treatment of ulcerative colitis was revolutionized by Brooke by way of a colectomy combined with an eversion ileostomy. This procedure is known to be associated with a number of complications that include skin excoriation, stenosis, intestinal obstruction, retraction or prolapse of the stoma, abscess and fistula formation, and ileitis. However, adenocarcinoma arising in the abnormally placed small intestinal mucosa 20 years or more after the initial operation is being increasingly recognized and reported. This article describes one such case and includes an extensive review of the current world literature on the subject of adenocarcinoma arising as a late complication of operation for ulcerative colitis.

Radical surgery for the solitary bony metastasis from renal-cell carcinoma.

We carried out excision of a solitary bony metastasis from renal-cell carcinoma in 25 patients in the hope that this would produce a prolonged disease-free interval. Two patients had excisions only, five had amputations and 18 had excision and endoprosthetic replacement. The one-, three- and five-year cumulative survival rates were 88%, 54% and 13%, respectively. There were three complications. One patient developed a local recurrence and three had problems related to the endoprosthesis. We recommend radical excision of a solitary bony metastasis from renal-cell carcinoma to achieve local control of the tumour for the remainder of the patient's life.

Novel shikonin derivatives targeting tubulin as anticancer agents.

In this study, we report the identification of a new shikonin-phenoxyacetic acid derivative, as an inhibitor of tubulin. A series of compounds were prepared; among them, compound 16 [(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(4- phenoxyphenyl) acetate] potently inhibited the function of microtubules, inducing cell growth inhibition, apoptosis of cancer cell lines in a concentration and time-dependent manner. Molecular docking involving 16 at the vinblastine binding site of tubulin indicated that a phenoxy moiety interacted with tubulin via hydrogen bonding with asparaginate (Asn) and tyrosine (Tyr). Analysis of microtubules with confocal microscopy demonstrated that 16 altered the microtubule architecture and exhibited a significant reduction in microtubule density. Cell cycle assay further proved that HepG2 cells were blocked in G2/M phase. Our study provides a new, promising compound for the development of tubulin inhibitors by proposing a new target for the anticancer activity of shikonin.

Does curettage without adjuvant therapy provide low recurrence rates in giant-cell tumors of bone?

UNLABELLED: Adjuvant treatment or filling agents have been recommended for reducing recurrence rates of giant-cell tumors of bone. However, reports of low recurrence rates without either caused us to question this concept. We retrospectively reviewed 193 patients treated during a 27-year period, comparing our results with historic controls. One hundred thirty-seven patients had curettage as a primary treatment, and of these, 26 (19%) had local recurrences. The local recurrence rate of giant-cell tumors confined to bone (Campanacci Grades I and II) was only 7% compared with 29% in tumors with extraosseous extension (Campanacci Grade III). Six patients (4%) had a fracture after curettage. Twenty-nine patients who were referred to us with local recurrences after treatment elsewhere had curettage, and 10 (34%) of these patients had local recurrences develop. Twenty-seven patients had excision as their primary treatment, and two (7%) of these patients had local recurrence develop. We recommend primary curettage for intraosseous giant-cell tumors without adjuvant treatment or filling agents, but tumors with soft tissue extension or with local recurrence require more aggressive treatment. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series--no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Epstein-Barr virus in B-cell lymphomas associated with chronic suppurative inflammation.

Chronic antigenic stimulation is considered to play an important role in neoplastic lymphoid transformation. This paper describes three cases of non-Hodgkin lymphomas (NHLs) associated with long-standing chronic suppuration. Two were primary bone lymphomas associated with long-standing chronic osteomyelitis and one was a primary skin lymphoma associated with chronic venous ulcers with a latent period of 13 years. All were diffuse large B-cell lymphomas, with plasmacytoid differentiation in two cases. Epstein-Barr virus (EBV)-encoded RNAs were demonstrated in virtually all tumour cells in all cases by in situ hybridization. Immunohistochemistry revealed EBV-encoded latent membrane protein (LMP)-1 expression in one case and BZLF1 protein expression in all three cases, whilst the EBV-encoded nuclear antigen (EBNA)-2 was not detected. Kaposi's sarcoma-associated herpesvirus (KSHV) sequences were absent in two cases studied. Our cases show similarities with pyothorax-associated pleural lymphomas reported mainly from Japan and recently from France, which are invariably associated with EBV. These findings suggest a causal effect of EBV in the development of this type of lymphoma complicating long-standing chronic suppuration. Localized immunodepression induced by chronic inflammation or immunosuppressive cytokines may favour the clonal proliferation of EBV-infected B cells.