Serum from patients with severe CHF downregulates eNOS expression and increases apoptosis. High levels of TNF-alpha likely play a role, but they cannot be the only factor responsible.

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Background-Endothelial apoptosis of atherosclerotic lesions is a possible determinant for the stable-to-vulnerable plaque transition.Recent data support the notion that plaque activation may be a pan-coronary process, advocating the existence of circulating triggers. Methods and Results-Serum from 40 healthy subjects (group 1) and 73 patients with stable angina (nϭ32; group 2) or acute coronary syndromes (nϭ41; group 3) was incubated with human umbilical vein endothelial cells. The percentage of apoptosis by flow cytometry and Fas, Bax, and Bcl-2 protein expression by immunoblotting were evaluated at entry in patients and control subjects and repeated after 12 months in group 3. At baseline, apoptotic nuclei were higher in group 3 (14Ϯ6%) than in group 2 (3.3Ϯ1.8%) and group 1 (1.35Ϯ0.8%) (PϽ0.001). Fas and Bcl-2 were increased in group 3 with respect to groups 1 and 2 (PϽ0.01). Coincubation of group 3 serum with anti-tumor necrosis factor-␣ and anti-interleukin-6 monoclonal antibodies did not affect the human umbilical vein endothelial cell apoptotic process, whereas addition of Trolox decreased apoptosis to Ͻ50%. The percentage of apoptosis in group 3 significantly correlated to the numbers of coronary complex lesions at angiography (rϭ0.58, PϽ0.0005). In group 3, apoptosis and the Bax/Bcl-2 ratio decreased at 1 year (PϽ0.0001, PϽ0.05 respectively). Conclusions-Serum from patients with acute coronary syndromes displays a proapoptotic effect on human endothelial cells, supporting the theory of the existence of circulating triggers potentially able to activate atherosclerotic lesions.

BACKGROUNDThe objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin‐dependent kinase inhibitor p27(Kip1) in patients with early‐stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers.METHODSImmunoreactivity for p27 protein was analyzed on tumor slides from 461 patients who were enrolled in the International Breast Cancer Study Group (IBCSG) Trial V (median follow‐up, 13 years), including 198 patients with lymph node negative disease and 263 patients with lymph node positive disease. Tumors with < 50% immunoreactive neoplastic cells were considered low expressors. Immunoreactivity for p27 was correlated with several clinicopathologic characteristics. Disease free survival (DFS) and overall survival were analyzed according to p27 immunoreactivity and treatment group.RESULTSIn the lymph node negative population, decreased p27 immunoreactivity was associated with higher tumor grade (P = 0.001) and HER‐2/neu overexpression (P = 0.04). In the lymph node positive population, low p27 expression was associated with higher tumor grade (P = 0.01), low expression of thymidylate synthase (P = 0.001), and higher Ki‐67 expression (P = 0.007). DFS was not significantly different according to p27 status in either lymph node negative patients (10‐year DFS: low p27 expression, 53% ± 5%; high p27 expression, 55% ± 5%) or in lymph node positive patients (10 year DFS: low p27 expression, 33% ± 4%; high p27 expression, 32% ± 4%). However, in the lymph node negative population, the benefit of one course of perioperative chemotherapy with cyclophosphamide, methotrexate, and 5‐fluorouracil was confined exclusively to patients with tumors that showed reduced p27 immunoreactivity (P = 0.03; test for interaction).CONCLUSIONSThis analysis indicates that p27 immunoreactivity has little if any prognostic value in patients with early‐stage breast carcinoma. However, these findings suggest that, in patients with breast carcinoma who have negative lymph node status, reduced p27 immunoreactivity is associated with HER‐2/neu overexpression and may be predictive of a benefit from the early administration of adjuvant chemotherapy. Cancer 2003;97:1591–600. © 2003 American Cancer Society.DOI 10.1002/cncr.11224

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The monoclonal antibody KP1, which recognizes the CD 68 antigen on macrophages and myeloid precursors, was tested on 28 malignant (primary and metastatic) melanomas, 28 naevi, and 17 skin biopsies showing either normal (10) or hyperplastic melanocytes (7). Sixteen of 20 primary melanomas and six of eight metastatic melanomas showed variable numbers of KP1 positive tumour cells. All but five benign melanocytic proliferations (two Spitz naevi and three intradermal naevi), as well as normal and hyperplastic melanocytes were negative. These results indicate that difficulties may occur with the use of KP1 in the differential diagnosis between melanomas and neoplasms derived from histiocytes-macrophages, and that the expression of CD 68 antigen might be related to tumour progression in melanocytic cells.