BackgroundThe chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model.MethodsNOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 μg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively.ResultsThe anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated.ConclusionsThe anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies.
Cytomegalovirus (CMV) infections are usually described in immunodeficient patients. In immunocompetent patients active infection is uncommon, consisting usually of a mononucleosis-like syndrome. Numerous reports show that CMV is a potential pathogen in the gastrointestinal tract, even in immunocompetent patients, where it can produce lesions from the mouth to the anus. We report herein an uncommon association of chronic inflammation of the papilla and viral CMV inclusions with distal cholangiocarcinoma in a 72-year-old woman who presented jaundice, choluria, acholia and generalized pruritus. At laparotomy, dilatation of the bile ducts and an enlarged head of the pancreas were found. Pancreatoduodenectomy was performed. Pathology revealed an enlarged papilla, due to chronic inflammation with CMV inclusions. Histological analysis revealed moderately differentiated ductal adenocarcinoma of the distal bile tract.
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