Fred E Bertrand's research while affiliated with University of Alabama at Birmingham and other places
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Publications (48)
Colorectal cancer (CRC) remains a challenging disease to treat due to several factors including stemness and epithelial to mesenchymal transition (EMT). Dysfunctional signaling pathways such as Notch and TGF-β contribute to these phenomena. We previously found that cells expressing constitutively active Notch1 also had increased expression of Smad3...
A role for cancer initiating cells (CIC) in tumor growth, drug resistance, relapse, and metastasis via epithelial to mesenchymal transition (EMT) has been supported by experimental evidence. It is well-documented that Notch-1 receptor signaling participates in stem cell maintenance and lineage commitment in various organs, including the colon, and...
Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also, the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promot...
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 aggressiv...
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA
Prostate cancer affects one in three men over the age of 60. Loss of expression or function of PTEN is the most commonly observed molecular defect in human prostate cancer. Thirty to 70% of clinical cases exhibit loss of this critical tumor suppressor. PTEN is an essential negat...
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA
Colorectal cancer (CRC) is the second leading cause of cancer death nationwide. In 2013, nearly 156,000 patients will be diagnosed with CRC. Surgical resection for early stage disease offers the best chance for cure; however, up to 30% of patients will relapse. Current models of...
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,...
Over the past decade, our understanding of the role that Notch-signaling has in tumorigenesis has shifted from leukemogenesis into cancers of solid tumors. Emerging data suggests that in addition to direct effects mediated through the canonical Notch pathway, Notch may participate in epithelial tumor development through regulation of pathways such...
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, e...
A hallmark of cancer is reactivation/alteration of pathways that control cellular differentiation during developmental processes. Evidence indicates that WNT, Notch, BMP and Hedgehog pathways have a role in normal epithelial cell differentiation, and that alterations in these pathways accompany establishment of the tumorigenic state. Interestingly,...
Gamma-glutamyl transferase (GGT1) is a cell membrane bound enzyme that functions in gamma-glutamyl cycling, to provide cells with intracellular glutathione (GSH). GGT1 has been recognized to participate in chemotherapeutic resistance of tumors to carboplatin and various alkylating agents by increasing GSH levels intracellularly, thus allowing the t...
Notch-1 is part of an evolutionarily ancient cell surface receptor signaling pathway that functions in the determination of stem/progenitor cell fate. The human genome encodes four Notch-receptors (Notch-1, -2, -3, and -4) and at least five Notch-ligands (Delta-1, -3, -4, Jagged-1, and-2). Signaling is initiated upon ligand binding to the Notch rec...
Automated classification of biological cells according to their 3D morphology is highly desired in a flow cytometer setting. We have investigated this possibility experimentally and numerically using a diffraction imaging approach. A fast image analysis software based on the gray level co-occurrence matrix (GLCM) algorithm has been developed to ext...
FDTD modeling and angle-resolved measurement of Mueller matrix elements have been conducted with suspensions of two white blood cell lines at three wavelengths. We found that S12 exhibits the largest difference.
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 prostat...
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 impor...
The homeobox (Hox) gene family encodes a group of transcription factors preferentially expressed during embryonic development and hematopoiesis. Deregulation of Hox gene expression is frequently associated with acute leukemia. HoxA9 is the most commonly overexpressed Hox gene in acute leukemia. However, little is known regarding specific pathways r...
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 re...
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 thes...
The homeobox (Hox) gene family encodes a group of transcription factors preferentially expressed during embryonic development and hematopoiesis. Overexpression of Hox genes is frequently associated with acute leukemia. HoxA9 is the most commonly overexpressed Hox gene in acute leukemia and forms part of a genetic signature that characterizes AML an...
The ability to identify specific chromosomes with certainty has been established by the development of several cytogenetic techniques based on staining. Here, we report the use of a new optical technique, laser tweezers and Raman spectroscopy (LTRS), to capture and manipulate chromosomes in order to obtain their spectral patterns for molecular anal...
The PTEN gene regulates multiple signaling pathways that influence cell proliferation, survival and differentiation. Loss of PTEN expression is closely linked with oncogenesis. Little is known regarding regulation of PTEN gene expression. The PTEN promoter region has been reported and is regulated in part by p53. In a previous study, we found that...
The Ras/Raf/MEK/ERK pathway plays a critical role in the transmission of signals from growth factor receptors to the nucleus
to regulate gene expression. Components of this pathway (e.g., Ras and B-Raf) are frequently mutated in human cancer. Mutations
at upstream receptors (e.g., epidermal growth factor receptor [EGFR] and Flt-3) and chimeric chro...
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, n...
The Insulin-like growth factor-1 receptor (IGF-1R) is overexpressed in a variety of tumors including breast, prostate and myeloma. Thus, IGF-1R and its downstream signaling effectors are good candidates for molecular-based targeted antitumor therapies. Indeed, protein inhibitors of IGF-1R signaling and IGF-1R blocking antibodies are undergoing clin...
We demonstrated that different numbered human chromosomes could be discriminated and sorted with confocal Raman-tweezers spectroscopy, and the result was confirmed with G-band technique.
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 upst...
Mutations in the Ras pathway have been detected in approximately 50% of hematopoietic malignancies. These mutations usually occur at KRAS, NRAS or upstream FLT3. Recent results from an Asian based leukemia study indicated that the BRAF gene is mutated in 4% of AMLs and 3% of NHL. We sought to determine whether the BRAF, KRAS, PI3K genes were mutate...
The Raf/MEK/ERK and PI3K/Akt kinase cascades are pivotal in transmitting signals from membrane receptors to transcription factors which regulate growth, apoptosis and chemotherapeutic drug resistance. Previously we determined that activated Raf-1 or Akt expression by themselves, did not relieve cytokine-dependence of FL5.12 hematopoietic cells. How...
Mammalian Notch-1 is part of an evolutionarily conserved family of transmembrane receptors best known for involvement in cell fate decisions. Mutations that result in Notch-1 activation result in T-lineage oncogenesis. In other cell lineages, however, studies have indicated that cooperation with cellular signaling pathways, such as Ras, is necessar...
Over the past 30 years, a relatively simple growth factor and its cognate receptor have provided seminal insights into the understanding of the genetic basis of cancer, as well as growth factor signalling. The epidermal growth factor (EGF), its cognate receptor (EGFR) and related family members have been shown to be important in normal, as well as...
v-ErbB is an oncogene related to the Epidermal Growth Factor Receptor (EGFR). EGFR overexpression has been observed in many pathological situations. There is a truncated form of EGFR, referred to as EGFvIII, which resembles v-ErbB in biological properties and is often expressed in certain human tumors. Aberrant EGFR expression in human cancers is o...
Epidermal growth factor (EGF) is commonly thought to affect the proliferation of many cells, especially epithelial cells. Aberrant expression of the receptor for EGF, (EGFR) or members of the EGFR family is often implicated in the etiology of many cancers. Ligation of the EGFR results in the activation of many downstream signaling pathways which ha...
Commentary to:
An Optimized Conditional Suicide Switch Using Doxycycline-Dependent Expression of Human tBid
Anja Knott, Lars Drueppel, Thomas Beyer, Kristin Garke, Christian Berens, Martin Herrmann, and Wolfgang Hillen
http://www.landesbioscience.com/journals/cbt/abstract.php?id=1658
B-lineage acute leukemia (B-ALL) cells often require stromal cell support for optimal proliferation and apoptotic resistance. In addition, stromal cell contact can promote resistance to chemotherapeutic agents. However, the precise biochemical pathways within the leukemic cell that are activated by the bone marrow microenvironment which result prom...
Bone marrow stromal cells are essential for the differentiation, survival and proliferation of normal and leukemic human B-lineage cells. Leukemic cells require stromal cell support for optimal proliferation and apoptotic resistance. Stromal cell contact can promote resistance to chemotherapeutic agents. In this study, we have made use of small mol...
A prior diagnosis of HIV increases the risk of lymphoma between 150 to 250- fold, depending on the subtype, as compared with the risk observed in the general population. The advent of highly active anti-retroviral therapy (HAART) has seen a dramatic reduction in AIDS morbidity and a modest reduction in the incidence of opportunistic infections alon...
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a phosphatase that removes phosphates primarily from lipids. It has also been called mutated in multiple advanced cancers 1 and transforming growth factor-beta regulated epithelial cell-enriched phosphatase 1. The best described substrate of PTEN is phosphatidyliniositol (3,4,5)-tr...
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 effect...
Infant acute lymphoblastic leukemia (ALL) is frequently characterized by the t(4;11)(q21;q23) cytogenetic abnormality encoding the MLL/AF4 oncogene, increased HOX gene expression and a pro-B/monocytoid phenotype. We have previously established a novel MLL/AF4-positive cell line, B-lineage 3 (BLIN-3), which retains several features of normal B-linea...
Novel approaches have been designed to treat leukemia based on our understanding of the genetic and biochemical lesions present in different malignancies. This meeting report summarizes some of the recent advances in leukemia treatment. Based on the discoveries of cellular oncogenes, chromosomal translocations, monoclonal antibodies, multidrug resi...
The most common chromosomal abnormality of infant acute lymphoblastic leukemia (ALL) is the t(4;11)(q21;q23) that gives rise to the MLL/AF4 fusion gene. Leukemic blasts expressing MLL/AF4 are arrested at an early progenitor stage with lymphoid or monocytoid characteristics. A novel B-lineage ALL cell line termed B-lineage-3 (BLIN-3) requiring human...
The Notch genes encode a conserved family of receptors that influence developmental fate in many species. Prior studies have indicated that Notch-1 and Notch-2 signaling influence the development of hematopoietic stems cells and thymocytes, but little is known regarding Notch expression and function in B-lineage cells. We analyzed the expression of...
Mammalian B-cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B-lineage and functional Ig gene rearrangement--culminating in expression of the pre-B-cell receptor (pre-BCR) and the BCR. Progression of cells through these checkpoints is profoundl...
Citations
... In contrast, in this study, MTTP expression was increased in the order of normal, LGG, and GBM and also was associated with the stage and age of patients with brain tumors (Figure 1, Table 2), suggesting that the function of MTTP was altered depending on kinds of cancer. For instance, high Notch signaling is associated with tumor grade and metastasis, but it has an inhibitory effect on GBM (19,20). Therefore, the role of MTTP in the occurrence and progression of cancers may be dependent on the cancer type. ...
... Notch signal regulates the cell proliferation (Mu et al., 2017), stemness (Jin et al., 2017) and Epithelial to Mesenchymal Transition (EMT) (Fender et al., 2014) of CRC. Similar to the Wnt/β-catenin pathway, deregulated Notch signaling pathway as well as its aberrant crosstalk with other pathways including the canonical Wnt signaling pathway are tightly associated with the development of CRC (Vinson et al., 2016). ...
... These pathogens are known to be opportunistic and can cause acute intestinal infections in patients suffering from IBD and CRC. Additionally, they have been linked to an increased risk of IBS and CRC [36][37][38][39][40]. Our research revealed a positive correlation between Peptostreptococcaceae abundance and the expression of host genes PYGB and NCK2 in IBD, but a negative correlation with the expression of host gene HAS2 in IBS. ...
... Subsequently, the increased phosphorylation of p38MAPK and GSK-3β was found in the xenograft co-injected with BMSCs. The activation of p38MAPK potentially influences GSK-3β and downstream β-catenin signaling pathways [33,34]. The activity of GSK-3β played a role in the proliferation of human ovarian cancer cells in laboratory settings (in vitro) and within living organisms (in vivo) [35]. ...
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... With various functions in cell growth, survival, and metabolism, PTEN, also known as phosphatase and tensin homolog, is an essential regulator in cellular signaling pathways (Álvarez-Garcia et al. 2019). Because PTEN is a lipid phosphatase, it dephosphorylates PIP, which prevents Akt activation and hence opposes the PI3K/Akt circuit (Bertrand et al. 2014). Due to this, downstream signaling necessary for cell survival and proliferation is adversely regulated (Carnero et al. 2008). ...
... GSK-3β plays a vital role in regulating various biological processes, including cell proliferation and apoptosis. Accumulating evidence indicates that GSK-3β can actively contribute to the transduction of inflammation-related pathways, such as NF-κB and Wnt/β-catenin (McCubrey et al., 2014). This involvement enables GSK-3β to modulate the production of inflammatory mediators and impact the progression of neuroinflammation. ...
... The Notch-1 pathway has been associated with the stemness process, which is necessary for several cancers, including CRC [39]. Notch-1 is a transmembrane receptor activated by binding a transmembrane substrate and is thought to play a role in cell-to-cell communication [40]. ...
... Binding of nerve growth factor to TrkA stimulates a signal transduction cascade that promotes neuron survival through inhibition of apoptotic proteins via the PI-3K/AKT pathway [158]- [160], through MEK/MAPK pathway stimulation of anti-apoptotic (pro-survival) proteins [161]- [163], and through upregulation of CREB [162] [163]. The MEK/MAPK pathway has also been shown to protect sympathetic neurons from cytokine arabinoside induced apoptosis and cerebellar neurons from apoptosis due to oxidative stress [163]- [166]. Several studies have illustrated the protective effect of NGF in animal models. ...
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... PTEN has been reported to be involved in PI3K-Akt-mTOR axis and JAK-STAT signaling pathway, and therefore participates in various biological processes (Chetram and Hinton, 2012;Gallaher and Steward, 2018;Mccubrey et al., 2008;Sun et al., 2011;Yuzugullu et al., 2016;Mccubrey et al., 2006). Accordingly, we investigated the effect of miR-26a/PTEN on activation of these two signaling pathways in H 2 O 2treated NMVCs. ...
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... Therefore, when doctors need to check whether a patient suffers from a certain disease, the most intuitive way is to detect whether WBCs in the human body have undergone quantitative changes or lesions [16,17]. In clinical practice, WBCs are generally identified by manual microscopy [18][19][20], which is time-consuming and labour-intensive. In addition, human errors are inevitable during the identifying process due to some human subjective factors. ...
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