Background: Apoptosis plays a major role in depleting CD4+ lymphocytes during infection with HIV-1. Few data exist on its role during HIV infection of children. Sensitivity of peripheral blood ...lymphocytes (PBLs) to apoptotic stimuli and the importance of the patient’s age remain unclear. Objectives: We sought to analyze the following: (1) markers of cell death-activation (CD95, CD45 isoforms, and CD28) in PBLs from vertically HIV-infected children of different ages before highly active antiretroviral therapy; (2) changes in other PBL populations; (3) PBL sensitivity to cell death and mitochondrial damages; and (4) role of age during progression of infection. Methods: Cell culture techniques and flow cytometry were used to analyze surface antigens, PBL susceptibility to apoptosis, or PBL susceptibility to change of mitochondrial membrane potential. Results: Donor age had a strong negative correlation with numbers of CD4+ and CD8+ T cells. Virgin T lymphocyte (CD45RA+, CD95–) levels and those of CD95+ cells showed no correlation with the children’s clinical status but did show a correlation with patient age. CD28– T lymphocytes were markedly augmented in HIV-infected children but were unrelated to stage of infection or age. A relevant decrease in B lymphocytes and an increase in natural killer cells were also found. Finally, PBLs from HIV-positive children had a marked tendency to undergo apoptosis and mitochondrial damage. Conclusion: Changes in PBL phenotype, increased expression of CD95, and high sensitivity to apoptosis suggest that a precocious aging of the immune system occurs in HIV-infected children. (J Allergy Clin Immunol 2001;108:439-45.)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The real practice of breast cancer diagnosis and treatment is often very different from guideline recommendations. Screening programs should minimize deviations from "best practice". The aim of the ...study was to compare cases detected by screening programs with cases that were not part of the public screening program, analyzing the diagnostic pathways from the first suspected breast problem to therapeutic intervention for breast cancer.
We interviewed a random sample of 268 women aged 49-70 years in three Italian regions (Lazio, Tuscany, Basilicata) who were treated for breast cancer, stratified by screening participation.
In the nonscreened group, 48% of women were symptomatic and 50% were diagnosed by preventive tests. The proportion of women treated within 30 days of diagnosis was significantly lower in the screened group, 21.3% vs 35.8% (P = 0.0003). The mean number of tests (mammography, ultrasonography, cytology and histology) performed in the screened group was significantly higher than in the nonscreened group, 3.7 vs 2.8 (P = 0.001). The percentage of women treated without a preoperative histological or cytological diagnosis was lower in the screened group than in the nonscreened group, 14% vs 25% (P = 0.024).
Participation in screening programs seems to lead to more appropriate disease management even for breast cancer cases treated at the same hospital.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We previously identified the aberrantly expressed cell cycle regulator cyclin B1 as a tumor antigen that can elicit both humoral and cellular immune responses in cancer patients. While cyclin B1 is ...only transiently expressed in normal cells, cancers of many tissue origins constitutively overexpress the cell cyclin in the cytoplasm, which correlates with poorer patient prognosis. We propose that this tumor-specific overabundance and cytoplasmic location of cyclin B1 leads to the presentation of high—and therefore immunogenic—concentrations of cyclin B1 peptides to the immune system. Our studies focused on the source of immune responses against cyclin B1 and the significance of these immune responses in the setting of cancer. To study the significance of the anti-cyclin B1 immune response in human cancer, we tested plasma from patients with non-small cell lung cancer (NSCLC) for anti-cyclin B1 IgG and demonstrated that a longer overall survival in patients with stage IB NSCLC is correlated with high levels of anti-cyclin B1 IgG. We also demonstrated that cyclin B1-specific antibody and T cell responses exist in healthy individuals who have no history of cancer. Further, the cyclin B1-specific T cells in healthy individuals are antigen experienced and in both CD4+ and CD8+ T cell compartments. We then sought to determine the potential significance of a preexisting anti-cyclin B1 immune response in the setting of cyclin B1+ tumor development. Using both transplantable and spontaneous mouse models of cyclin B1+ tumors, we demonstrated that vaccination against cyclin B1 prior to the administration or spontaneous development of cyclin B1+ tumors inhibits tumor growth. Finally, given that viral infection has been shown to lead to overexpression of cyclin B1, we proposed that the anti-abnormal self protein, anti-tumor antigen immune responses we observed in healthy people were a result of a virus infection. The extension of that hypothesis is that infections with viruses can train the immune system to recognize abnormal expression of self proteins and therefore protect from cancers that abnormally express those proteins as well. We demonstrated that infection with ectromelia, a murine pox virus, protects from tumor challenge.
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