Biomedical subjects

Vassiliki L Tsikitis

Publications and source records attributed to Vassiliki L Tsikitis.

3 recordsLinked to original sources

PubMed2006

Biology of ductal carcinoma in situ classification based on biologic potential.

Incidence of ductal carcinoma in situ (DCIS) has increased significantly during the last decade, comprising almost 20% of all breast cancers diagnosed today. DCIS is composed of malignant breast duct epithelial cells that have clonally proliferated and accumulated within the mammary duct lumen. It comprises a group of heterogeneous tumors with varying biologic behavior rendering its classification and management challenging. By definition, DCIS does not invade through the basement membrane; it is a preinvasive malignancy and systemic disease is nonexistent. The basis of treatment is to prevent progression into an invasive cancer such as ductal carcinoma. Most current DCIS classification schemes do not predict its potential to progress to invasive disease. In this review the natural history of DCIS, as it relates to its biologic potential to progress to invasive disease, is summarized, and a broad classification system that may provide a guideline for patient management is proposed.

Biomarkers, Tumor↗

PubMed2004

The lectin-like domain of complement receptor 3 protects endothelial barrier function from activated neutrophils.

The adhesion of neutrophils to endothelial cells is a central event leading to diapedesis and involves the binding of the I-domain of beta(2) integrins (CD11/CD18) to endothelial ICAMs. In addition to the I-domain, the beta(2) integrin complement receptor 3 (CR3) (CD11b/CD18) contains a lectin-like domain (LLD) that can alter leukocyte functions such as chemotaxis and cytotoxicity. The present study demonstrates that, in contrast to the CR3 I-domain, Ab blockade of the CR3 LLD has no role in mediating neutrophil-induced loss of endothelial barrier function. However, activation of CR3 with the LLD agonist beta-glucan protects the barrier function of endothelial cells in the presence of activated neutrophils and reduces transendothelial migration without affecting adhesion of the neutrophils to the endothelium. The LLD site-specific mAb VIM12 obviates beta-glucan protection while activation of the LLD by VIM12 cross-linking mimics the beta-glucan response by both preserving endothelial barrier function and reducing neutrophil transendothelial migration. beta-glucan has no direct effect on endothelial cell function in the absence of activated neutrophils. These findings demonstrate that signaling through the CR3 LLD prevents neutrophil-induced loss of endothelial barrier function and reduces diapedesis. This suggests that the LLD may be a suitable target for oligosaccharide-based anti-inflammatory therapeutics.

Chemotaxis, Leukocyte↗

PubMed2004

Beta-glucan affects leukocyte navigation in a complex chemotactic gradient.

BACKGROUND: Polymorphonuclear leukocytes (PMNs) must traverse endogenous chemotactic gradients (interleukin 8 [IL-8]) before reaching target chemoattractants (fMLP [N-formylmethionine-leucine-phenylalanine], C5a) produced at a site of bacterial infection. Complement receptor 3 (CR3; CD11b/CD18) contains 2 distinct binding sites, one that mediates adhesion and a lectin-like domain (LLD) that binds polysaccharides of microbial origin. This laboratory previously reported an increase in the chemotactic capacity of PMNs toward fMLP upon ligation of the CR3 LLD with beta-glucan, a CR3 agonist. Current studies sought to determine the effect of beta-glucan on PMN navigation toward other chemoattractants alone and in a competing chemotactic environment. METHODS: Migration was assessed by serum agarose overlay with the use of chambered slides containing or not, beta-glucan. Migration of human PMNs at 37 degrees C for 2 hours was evaluated toward C5a or IL-8 alone and in competing gradients. Selected groups were treated with anti-CR3-blocking antibodies. The number of chemotactic cells was quantified by microscopy. RESULTS: beta-glucan significantly enhanced chemotaxis toward C5a and suppressed that toward IL-8 in a CR3-dependent fashion. In the competing chemotactic gradient assays (C5a vs IL-8), beta-glucan further enhanced migration toward C5a while not affecting that toward IL-8. CONCLUSIONS: beta-glucan selectively upregulates PMN chemotaxis toward C5a while suppressing chemotaxis toward IL-8.

Cell Movement↗