Fred E. Bertrand

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The roles of the JAK/STAT, Raf/MEK/ERK and PI3K/Akt signal transduction pathways and the BCR-ABL oncoprotein in leukemogenesis and their importance in the regulation of cell cycle progression and apoptosis are discussed in this review. These pathways have evolved regulatory proteins, which serve to limit their proliferative and antiapoptotic effects. Small(More)
Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological properties have been elucidated, including their distinct replicative properties, cell surface phenotypes, their increased resistance to chemotherapeutic drugs and the involvement of growth-promoting chromosomal translocations. Of particular importance is(More)
The Ras/Raf/MEK/ERK and PI3K/PTEN/AKT signaling cascades play critical roles in the transmission of signals from growth factor receptors to regulate gene expression and prevent apoptosis. Components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf, PI3K, PTEN, Akt). Also, mutations occur at genes encoding upstream(More)
Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated(More)
The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer,(More)
Prostate tumorigenesis is associated with loss of PTEN gene expression. We and others have recently reported that PTEN is regulated by Notch-1 signaling. Herein, we tested the hypothesis that alterations of the Notch-1 signaling pathway are present in human prostate adenocarcinoma and that Notch-1 signaling regulates PTEN gene expression in prostate cells.(More)
The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are frequently activated in leukemia and other hematopoietic disorders by upstream mutations in cytokine receptors, aberrant chromosomal translocations as well as other genetic mechanisms. The Jak2 kinase is frequently mutated in many myeloproliferative disorders. Effective targeting of these(More)
Mixed lineage leukaemia gene-partial tandem duplications (MLL-PTD) characterise acute myeloid leukaemia (AML) with trisomy 11 and AML with a normal karyotype. MLL-PTD confer a worse prognosis with shortened overall and event free survival in childhood and adult AML. In spite of these clinical observations, the leukaemogenic mechanism has, so far, not been(More)
Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism,(More)
Colorectal cancer (CRC) is the third leading cause of cancer death in the United States, resulting in an average of 50,000 deaths per year. Surgery and combination chemotherapy comprise current treatment strategies. However, curative options are limited if surgery and chemotherapy are unsuccessful. Several studies have indicated that CRC aggressiveness and(More)