The Ability to Generate Senescent Progeny as a Mechanism Underlying Breast Cancer Cell Heterogeneity

Background Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity. Methodology/Principal Findings A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21Cip1 correlated with senescence in these cell lines. p21Cip1 knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and "normal-like" tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice. Conclusions/Significance Luminal A and "normal-like" breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential. © 2010 Mumcuoglu et al

Severe Lactic Acidosis Associated with Burkitt's Lymphoma

Lactic acidosis is a metabolic acidosis caused by either overproduction or underutilization of lactic acid. Overproduction of lactic acid, known as type A lactic acidosis, is frequent in critically ill patients with hypoperfusion states. Underutilization of lactic acid, known as type B lactic acidosis, is caused by many reasons, including hepatic and liver failure, thiamine deficiency, toxins, drugs, and certain malignancies such as lymphomas and leukemias. We report a patient with severe lactic acidosis and Burkitt's lymphoma without any signs of hypoperfusion that is relieved with chemotherapy

Effects of Industrial Lead Expossure on Coagulation System

Purpose: Lead is environmental and/or occupational toxicant. It has been known to induce hematological disturbance during haematopoiesis. However, it has not well known whether it has effects on coagulation system or not. Therefore, we aimed to investigate how coagulation system is affected by the level of elevated blood lead. Material and Methods: Fifty-two occupational lead exposure patients applied with load intoxication symptoms. Blood examples of patients were obtained for lead level, platelet count, in-vitro bleeding time, prothrombine time, partial thromboplastine time (aPTT), fibrinogen, thrombine time, protein C, protein S and antithrombine III. The patients are evaluated according to three groups as mild, moderate and severe. Results: Blood lead levels were mean 71,15 +/- 18,19 mu g/dl. Mean values results of primary and secondary hemostasis and physiological coagulation inhibitors tests were in normal ranges, except fibrinogen degree. Despite mean fibrinogen degree being under normal ranges, statistically significant difference between the groups was not detected. Mean aPTT and protein S degrees were in normal ranges, however, compared with the mild-toxicated group statistically important prolongment in aPTT and reducement in protein S degrees detected in moderate-toxicated group. Conclusion: As a result, although our results need suggestion by in vivo and in vitro studies, it is concluded that haemostatic parameters excluding fibrinogen were not effected by mild and moderate degree elevation of blood lead

Changes in CD34+cell count in peripheral blood after whole blood donation

Aim: We aimed to investigate the change in the number of stem cells and white cells in the early period following blood donation

Can low-dose preemptive valganciclovir replace standard intravenous ganciclovir treatment in recipients of allogeneic stem cell transplantation?

The aim of this retrospective study was to compare the efficacy and safety of standard intravenous ganciclovir (GCV) with low-dose oral valganciclovir (VGC) in preemptive treatment of cytomegalovirus (CMV) infection in patients who received allogeneic stem cell transplantation (ASCT). Fifty-nine adult ASCT patients with asymptomatic 68 CMV reactivations were included. For preemptive CMV treatment, VGC (900 mg/day) in 44 reactivations or GCV (5 mg/kg twice daily during the first week and once daily afterwards) in 24 CMV reactivations were administered for 21 days. Two consecutive negative results for PCR and/or CMV antigenemia were considered as treatment success. All patients with CMV reactivations were on immunosuppressive treatment. While no positivity was identified in any of the patients who received GCV on day 21, low-titer CMV positivity was noted in three of the patients in the VGC group (P = 0.264). In all three patients, VGC was continued at same dose and no positivity result was detected after 2-3 weeks. Low-grade neutropenia and high grade thrombocytopenia were significantly higher in the GCV group than in the VGC group (P = 0.018 and P = 0.04 respectively). Preemptive strategy of oral low-dose VGC appears preferable to the prevention of CMV disease in ASCT. These results require confirmation in prospective larger clinical studies