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  • 1
    Publication Date: 1998-03-07
    Description: The spindle checkpoint regulates the cell division cycle by keeping cells with defective spindles from leaving mitosis. In the two-hybrid system, three proteins that are components of the checkpoint, Mad1, Mad2, and Mad3, were shown to interact with Cdc20, a protein required for exit from mitosis. Mad2 and Mad3 coprecipitated with Cdc20 at all stages of the cell cycle. The binding of Mad2 depended on Mad1 and that of Mad3 on Mad1 and Mad2. Overexpression of Cdc20 allowed cells with a depolymerized spindle or damaged DNA to leave mitosis but did not overcome the arrest caused by unreplicated DNA. Mutants in Cdc20 that were resistant to the spindle checkpoint no longer bound Mad proteins, suggesting that Cdc20 is the target of the spindle checkpoint.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hwang, L H -- Lau, L F -- Smith, D L -- Mistrot, C A -- Hardwick, K G -- Hwang, E S -- Amon, A -- Murray, A W -- New York, N.Y. -- Science. 1998 Feb 13;279(5353):1041-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California at San Francisco, San Francisco, CA 94143-0444, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9461437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anaphase ; Anaphase-Promoting Complex-Cyclosome ; Cadherins ; Calcium-Binding Proteins/metabolism ; *Carrier Proteins ; Cdc20 Proteins ; Cdh1 Proteins ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; DNA Damage ; DNA Replication ; Fungal Proteins/chemistry/*metabolism ; Ligases/metabolism ; Mad2 Proteins ; *Mitosis ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/metabolism ; Phosphoproteins/metabolism ; *Repressor Proteins ; Saccharomyces cerevisiae/*cytology/*metabolism ; *Saccharomyces cerevisiae Proteins ; Spindle Apparatus/*metabolism ; *Ubiquitin-Protein Ligase Complexes ; Ubiquitin-Protein Ligases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-02-22
    Description: Retrospective clinical studies have used immune-based biomarkers, alone or in combination, to predict survival outcomes for women with breast cancer (BC); however, the limitations inherent to immunohistochemical analyses prevent comprehensive descriptions of leukocytic infiltrates, as well as evaluation of the functional state of leukocytes in BC stroma. To more fully evaluate this complexity, and to gain insight into immune responses after chemotherapy (CTX), we prospectively evaluated tumor and nonadjacent normal breast tissue from women with BC, who either had or had not received neoadjuvant CTX before surgery. Tissues were evaluated by polychromatic flow cytometry in combination with confocal immunofluorescence and immunohistochemical analysis of tissue sections. These studies revealed that activated T lymphocytes predominate in tumor tissue, whereas myeloid lineage cells are more prominant in “normal” breast tissue. Notably, residual tumors from an unselected group of BC patients treated with neoadjuvant CTX contained increased percentages of infiltrating myeloid cells, accompanied by an increased CD8/CD4 T-cell ratio and higher numbers of granzyme B-expressing cells, compared with tumors removed from patients treated primarily by surgery alone. These data provide an initial evaluation of differences in the immune microenvironment of BC compared with nonadjacent normal tissue and reveal the degree to which CTX may alter the complexity and presence of selective subsets of immune cells in tumors previously treated in the neoadjuvant setting.
    Keywords: Breast Cancer Special Feature
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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