Koilocytes indicate a role for human papilloma virus in breast cancer

Background: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. Methods: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. Results: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). Interpretation: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.6 page(s

The interstitium in cardiac repair: role of the immune-stromal cell interplay

Cardiac regeneration, that is, restoration of the original structure and function in a damaged heart, differs from tissue repair, in which collagen deposition and scar formation often lead to functional impairment. In both scenarios, the early-onset inflammatory response is essential to clear damaged cardiac cells and initiate organ repair, but the quality and extent of the immune response vary. Immune cells embedded in the damaged heart tissue sense and modulate inflammation through a dynamic interplay with stromal cells in the cardiac interstitium, which either leads to recapitulation of cardiac morphology by rebuilding functional scaffolds to support muscle regrowth in regenerative organisms or fails to resolve the inflammatory response and produces fibrotic scar tissue in adult mammals. Current investigation into the mechanistic basis of homeostasis and restoration of cardiac function has increasingly shifted focus away from stem cell-mediated cardiac repair towards a dynamic interplay of cells composing the less-studied interstitial compartment of the heart, offering unexpected insights into the immunoregulatory functions of cardiac interstitial components and the complex network of cell interactions that must be considered for clinical intervention in heart diseases

Efficient scavenger receptor-mediated uptake and cross-presentation of negatively charged soluble antigens by dendritic cells

Exogenous antigens endocytosed in large amounts by antigen-presenting cells (APC) are presented on major histocompatibility complex (MHC) class I molecules as well as on class II molecules, a process called cross-presentation. Among APC, dendritic cells (DC) play a key role in cross-presentation by transporting internalized antigen to the cytosol. The present study shows that ovalbumin (OVA) introduced with negative charges by succinylation (Suc-OVA), maleylation (Mal-OVA) or cis-aconitylation (Aco-OVA) was efficiently taken up by DC via scavenger receptors (SR). Mal-OVA and Aco-OVA were efficiently cross-presented by DC, while cross-presentation of Suc-OVA was hardly observed. MHC class I presentation of acylated OVA introduced directly into the cytosol was inefficient and presentation of exogenous native OVA but not of Aco-OVA was markedly augmented by chloroquine, an inhibitor of endosomal acidification, suggesting that deacylation in endosomes or lysosomes is necessary for cross-presentation of acylated OVA. MHC class I presentation of exogenous native OVA and Aco-OVA by DC was blocked by lactacystin and brefeldin A, demonstrating that exogenous antigens taken up by DC are cross-presented through the conventional cytosolic pathway. Therefore, SR-mediated delivery of antigen to DC leads to efficient cross-presentation, although the pathway of chemical modification should be considered