Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic.

Purpose: Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment.

Methods: Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting.

Features of triple-negative breast cancer: Analysis of 38,813 cases from the national cancer database.

The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB).

Accelerating stem cell proliferation by down-regulation of cell cycle regulator p21.

Background: Tissue engineering is often limited by the time required for culture expansion of cells necessary for scaffold seeding. Cell cycle regulators control entry and exit into the cell cycle and as such regulate cellular proliferation rates. The authors hypothesized that transient alteration in cell cycle regulators can be utilized as a means to accelerate stem cell proliferation.

Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell proliferation.

The t(7;11)(p15;p15) translocation, observed in acute myelogenous leukemia and myelodysplastic syndrome, generates a chimeric gene where the 5' portion of the sequence encoding the human nucleoporin NUP98 protein is fused to the 3' region of HOXA9. Here, we show that retroviral-mediated enforced expression of the NUP98-HOXA9 fusion protein in cord blood-derived CD34(+) cells confers a proliferative advantage in both cytokine-stimulated suspension cultures and stromal coculture. This advantage is reflected in the selective expansion of hematopoietic stem cells as measured in vitro by cobblestone area-forming cell assays and in vivo by competitive repopulation of nonobese diabetic/severe combined immunodeficient mice.

Molecular strategies for detection and quantitation of clonal cytotoxic T-cell responses in aplastic anemia and myelodysplastic syndrome.

Immune mechanisms are involved in the pathophysiology of aplastic anemia (AA) and myelodysplastic syndrome (MDS). Immune inhibition can result from cytotoxic T cell (CTL) attack against normal hematopoiesis or reflect immune surveillance. We used clonally unique T-cell receptor (TCR) variable beta-chain (VB) CDR3 regions as markers of pathogenic CTL responses and show that while marrow failure syndromes are characterized by polyclonal expansions, overexpanded clones exist in these diseases and can serve as investigative tools.

In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing.

Background: Aplastic anaemia is a bone-marrow-failure syndrome characterised by low blood-cell counts and fatty bone marrow. In most cases, no obvious aetiological factor can be identified. However, clinical responses to immunosuppression strongly suggest an immune pathophysiology.

Shared and individual specificities of immunodominant cytotoxic T-cell clones in paroxysmal nocturnal hemoglobinuria as determined by molecular analysis.

Objective: Similar immune mechanisms have been suggested to operate in aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH), and the presence of PNH clones in AA may indicate that an immune reaction directed against hematopoietic stem cells may be responsible for the immune selection pressure leading to PNH evolution. We previously described expansions of selective cytotoxic T-lymphocyte (CTL) clones in AA patients.

Materials And Methods: We applied a molecular analysis of the T-cell receptor repertoire to study the characteristics of CTL response in patients with various forms of PNH.

Molecular analysis of TCR clonotypes in LGL: a clonal model for polyclonal responses.

Large granular lymphocytic (LGL) leukemia is a clonal lymphoproliferative disorder of CTL associated with cytopenias resulting from an immune and cytokine attack on hemopoietic progenitor cells. Extreme clonality of CTL expansions seen in LGL leukemia makes it an ideal model to study the role of the T cell repertoire in other less-polarized immune-mediated disorders. Complementarity-determining region 3 (CDR3) of the TCR is a unique Ag-specific region that can serve as a molecular marker, or clonotype, of the disease-specific T cells.

Diamond blackfan anemia stem cells fail to repopulate erythropoiesis in NOD/SCID mice.

Diamond Blackfan Anemia (DBA) is a congenital disorder characterized by decreased red blood cell production and developmental abnormalities. We herein show that DBA progenitors produced lower numbers of phenotypically normal erythroid colonies in vitro, whereas nonerythroid colonies were normally abundant and developed. To determine whether DBA stem cells are capable of producing early erythroid, monocyto-granulocytic, and lymphoid progenitors in vivo we used a mouse xenotransplantation model.

Application of the molecular analysis of the T-cell receptor repertoire in the study of immune-mediated hematologic diseases.

The basis for the vast recognition spectrum of the T-cell receptor (TCR) can be determined by the rearrangement and recombination of the variable, diversity and joining regions of the variable portions of beta (B) and alpha (A) chains as well as their recombination and modification. Analysis of the TCR rearrangement has been routinely used to detect clonality for the diagnosis of lymphoid malignancies. However, molecular analysis of the TCR repertoire can be a powerful tool in the study of T-cell responses to pathogens and in autoimmune diseases.

Mitochondria play a central role in apoptosis induced by alpha-tocopheryl succinate, an agent with antineoplastic activity: comparison with receptor-mediated pro-apoptotic signaling.

alpha-Tocopheryl succinate (alpha-TOS) is a semisynthetic vitamin E analogue with high pro-apoptotic and anti-neoplastic activity [Weber, T et al. (2002) Clin. Cancer Res.

Expression of genes regulating angiogenesis in human circulating hematopoietic cord blood CD34+/CD133+ cells.

Objectives: Human CD34+ cells represent a heterogeneous population of immature cells which may differentiate to various cell types. The aim of the study was to determine angiogenesis regulating genes expression in CD34+ cells, their subpopulations, and during their differentiation induced by hematopoietic growth factors.

Material And Methods: We have measured the expression of angiogenesis regulating genes angiopoietin-1 (Ang-1), angiopoietin-1 (Ang-2) and their receptor Tie-2, vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2 in sorted population of CD34+ and CD34+/CD133+ cells from human cord blood and bone marrow, and in their differentiating progeny, using real time reverse transcriptase polymerase chain reaction.