Perez Alamino R.,Health science Center |
Espinoza L.R.,Health science Center |
Zea A.H.,Stanley ott Cancer Center
Clinical Rheumatology | Year: 2013
IgG4-related disease is defined as a multi-organ systemic disorder with pathological findings affecting a wide range of organ systems. The condition unifies a large number of clinical diagnoses previously considered as being confined to single organ systems. At present, several issues related to its pathophysiology remained controversial, including the natural history of the disease, the pathogenic role of IgG4, and its use as a biomarker. Glucocorticoids are considered the treatment of choice for remission induction of IgG4-related disease manifestations; however, concerns regarding duration of therapy and management of refractory disease remained to be elucidated. © 2013 Clinical Rheumatology.
Lin T.L.,Stanley ott Cancer Center |
Lin T.L.,Health science Center New Orleans |
Smith B.D.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
American Journal of the Medical Sciences | Year: 2011
Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with variable clinical outcomes. Emerging data has identified molecular markers that provide additional prognostic information to better classify these patients into those with a more favorable prognosis and those with an unfavorable prognosis who may require more aggressive or investigational therapies. Markers such as mutations in nucleophosmin 1 gene and CCAAT/enhancer binding protein alpha gene have been associated with a more favorable prognosis in CN-AML. In contrast, FMS-related tyrosine kinase 3 mutations, partial tandem duplication of mixed-lineage leukemia gene and overexpression of brain and acute leukemia, cytoplasmic gene are associated with inferior clinical outcomes. In this article, the authors discuss the classical clinical features of AML and the importance of cytogenetics that predict prognosis in AML. They review the best-described molecular markers in CN-AML and their significance to clinical decision making in CN-AML. © 2011 Lippincott Williams & Wilkins.
Rathinam R.,Stanley ott Cancer Center |
Alahari S.K.,Stanley ott Cancer Center
Cancer and Metastasis Reviews | Year: 2010
Adhesion of breast cancer cells is supported by various integrins. Cell adhesion is critical for maintenance of both three-dimensional and normal function of these tissues. Several integrins have been shown to have higher expression levels in metastatic cancers and have been implicated in degrading basement membrane by interacting with proteolytic enzymes. This suggests that a group of integrins plays an important role in migration and invasion through the remodeling of the extracellular matrix. In this review, we highlight recent advances in our understanding of how integrins regulate breast cancer through modulation of the actin cytoskeleton and the mechanisms that regulate this process. Also, we highlight the importance of integrin-binding proteins in cell migration and mechanisms that operate in invasive cells, during breast cancer progression. © 2010 Springer Science+Business Media, LLC.
Stalder M.W.,Louisiana State University Health Sciences Center |
Anthony C.T.,Louisiana State University Health Sciences Center |
Woltering E.A.,Louisiana State University Health Sciences Center |
Woltering E.A.,Stanley ott Cancer Center
Journal of Surgical Research | Year: 2011
Background: High doses (10 nM) of epothilone B, a microtubule stabilizer, will inhibit the development of human tumor-derived angiogenesis following short (14 d) drug exposure times. Metronomic dosing regimes use lower drug doses and prolonged drug exposure times in an attempt to decrease toxicity compared with standard dosing schedules. We hypothesized that epothilone B would be an effective anti-angiogenic agent when administered at very low doses over an extended period of time. Methods: Fragments of four fresh human tumors were cultured in a fibrin-thrombin matrix and maintained in nutrient media plus 20% fetal bovine serum (FBS) for 56 d. Tumor fragments (n = 40-60 per group) were exposed to weekly doses of epothilone B at concentrations of 10, 5, 1, 0.5, or 0.1 nM. All of these concentrations are clinically achievable. Tumor angiogenesis was assessed weekly on d 14-56 using a validated visual grading system. This system rates neovessel growth, density, and length on a 0-16 scale [angiogenic index, (AI)]. The average change in AI between d 14 and 56 was calculated for all samples and used to evaluate the metronomic response. Results: Epothilone B produced a dose-dependent anti-angiogenic response in all tumors. Two of the four tumors demonstrated a clear and significant metronomic anti-angiogenic effect over time. Conclusions: Epothilone B, when dosed by a metronomic schedule may have a significant anti-angiogenic effect on human solid tumors. This study provides evidence for the potential use of epothilone B on a metronomic dosing schedule. © 2011 Elsevier Inc. All rights reserved.
Subramani D.,Stanley ott Cancer Center |
Alahari S.K.,Stanley ott Cancer Center
Molecular Cancer | Year: 2010
The RAS (rat sarcoma) superfamily of small GTPases is broadly subdivided into five groups: Ras, Rho, Rab, Ran, and Arf. Rab family proteins are important in regulating signal transduction and cellular processes such as differentiation, proliferation, vesicle transport, nuclear assembly, and cytoskeleton formation. However, some Rab proteins have been reported to be necessary for the adhesion and migration of cancer cells. Although Ras and Rho family members have been strongly implicated in cancer progression, knowledge of Rabs action in this regard is limited. Some reports have also linked Rab GTPases with cancer cell migration and invasiveness. This review discusses the implications of the involvement of Rabs in malignant transformation and cancer therapy through integrin-mediated signaling events, with particular emphasis on breast cancer. © 2010 Subramani and Alahari; licensee BioMed Central Ltd.
Alahari S.,Stanley ott Cancer Center
MicroRNA in Cancer | Year: 2013
The field of microRNA biology is really emerging in the last couple of years. Several investigators highlighted the importance of miRNAs in cancer. Although there is so much literature on microRNAs exist, a comprehensive book is still not available. Thus this book will be a great use to the scientists in the field of cancer biology. In addition, this book will be a good source of information for undergraduate, graduate students who want to develop their research careers in cancer biology. © 2013 Springer Science+Business Media Dordrecht.
Ghonim M.A.,Stanley ott Cancer Center |
Ghonim M.A.,Al - Azhar University of Egypt |
Pyakurel K.,Stanley ott Cancer Center |
Ju J.,Stanley ott Cancer Center |
And 8 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015
Background We reported that DNA-dependent protein kinase (DNA-PK) is critical for the expression of nuclear factor κB-dependent genes in TNF-α-treated glioblastoma cells, suggesting an involvement in inflammatory diseases. Objective We sought to investigate the role of DNA-PK in asthma. Methods Cell culture and ovalbumin (OVA)- or house dust mite-based murine asthma models were used in this study. Results DNA-PK was essential for monocyte adhesion to TNF-α-treated endothelial cells. Administration of the DNA-PK inhibitor NU7441 reduced airway eosinophilia, mucus hypersecretion, airway hyperresponsiveness, and OVA-specific IgE production in mice prechallenged with OVA. Such effects correlated with a marked reduction in lung vascular cell adhesion molecule 1 expression and production of several cytokines, including IL-4, IL-5, IL-13, eotaxin, IL-2, and IL-12 and the chemokines monocyte chemoattractant protein 1 and keratinocyte-derived chemokine, with a negligible effect on IL-10/IFN-γ production. DNA-PK inhibition by gene heterozygosity of the 450-kDa catalytic subunit of the kinase (DNA-PKcs+/-) also prevented manifestation of asthma-like traits. These results were confirmed in a chronic model of asthma by using house dust mite, a human allergen. Remarkably, such protection occurred without causing severe combined immunodeficiency. Adoptive transfer of TH2-skewed OT-II wild-type CD4+ T cells reversed IgE and TH2 cytokine production but not airway hyperresponsiveness in OVA-challenged DNA-PKcs+/- mice. DNA-PK inhibition reduced IL-4, IL-5, IL-13, eotaxin, IL-8, and monocyte chemoattractant protein 1 production without affecting IL-2, IL-12, IFN-γ, and interferon-inducible protein 10 production in CD3/CD28-stimulated human CD4+ T cells, potentially by blocking expression of Gata3. These effects occurred without significant reductions in T-cell proliferation. In mouse CD4+ T cells in vitro DNA-PK inhibition severely blocked CD3/CD28-induced Gata3 and T-bet expression in CD4+ T cells and prevented differentiation of TH1 and TH2 cells under respective TH1- and TH2-skewing conditions. Conclusion Our results suggest DNA-PK as a novel determinant of asthma and a potential target for the treatment of the disease. © 2014 American Academy of Allergy, Asthma & Immunology.
Boggiatto P.M.,Iowa State University |
Martinez P.A.,Iowa State University |
Pullikuth A.,Health science Center |
Jones D.E.,Iowa State University |
And 5 more authors.
Microbes and Infection | Year: 2014
Leishmania amazonensis infection promotes alteration of host cellular signaling and intracellular parasite survival, but specific mechanisms are poorly understood. We previously demonstrated that L. amazonensis infection of dendritic cells (DC) activated extracellular signal-regulated kinase (ERK), an MAP-kinase kinase kinase, leading to altered DC maturation and non-healing cutaneous leishmaniasis. Studies using growth factors and cell lines have shown that targeted, robust, intracellular phosphorylation of ERK1/2 from phagolysosomes required recruitment and association with scaffolding proteins, including p14/MP1 and MORG1, on the surface of late endosomes. Based on the intracellular localization of L. amazonensis within a parasitophorous vacuole with late endosome characteristics, we speculated that scaffolding proteins would be important for intracellular parasite-mediated ERK signaling. Our findings demonstrate that MP1, MORG1, and ERK all co-localized on the surface of parasite-containing LAMP2-positive phagolysosomes. Infection of MEK1 mutant fibroblasts unable to bind MP1 demonstrated dramatically reduced ERK1/2 phosphorylation following L. amazonensis infection but not following positive control EGF treatment. This novel mechanism for localization of intracellular L. amazonensis-mediated ERK1/2 phosphorylation required the endosomal scaffold protein MP1 and localized to L. amazonensis parasitophorous vacuoles. Understanding how L. amazonensis parasites hijack host cell scaffold proteins to modulate signaling cascades provides targets for antiprotozoal drug development. © 2014 Institut Pasteur.
Kher S.S.,Health science Center |
Struckhoff A.P.,Stanley ott Cancer Center |
Alberts A.S.,Van Andel Research Institute |
Worthylake R.A.,Health science Center
PLoS ONE | Year: 2014
Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF) family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module. © 2014 Kher et al.
Struckhoff A.P.,Stanley ott Cancer Center |
Del Valle L.,Stanley ott Cancer Center
Methods in Molecular Biology | Year: 2013
Cell cultures constitute an important tool for research as a way to reproduce pathological processes in a controlled system. However, the culture of brain-derived cells in monolayer presents significant challenges that obscure the fidelity of in vitro results. After a few number of passages, glial and neuronal cells begin to lose their morphological characteristics, and most importantly, their specific cellular markers and phenotype. In recent years, the discovery of Neural Progenitor Cells and the methodology to culture them in suspension maintaining their potentiality while still retaining the ability to differentiate into astrocytes, oligodendrocytes, and neurons have made significant contributions to the fields of neuroscience and neuropathology. In the brain, progenitor cells are located in the Germinal Matrix, in the subventricular zone and play an essential role in the homeostasis of the brain by providing the source to replace differentiated cells that have been lost or damaged by different pathological processes, such as injury, genetic conditions or disease. The discovery of these Neural Stem Cells in an organ traditionally thought to have limited or no regenerative capacity has open the door to the development of novel treatments, which include cell replacement therapy. Here we describe the culture and differentiation of neural progenitor cells from Neurospheres, and the phenotyping of the resulting cells using immunocytochemistry. The immunocytological methods outlined are not restricted to the analysis of Neurosphere-derived cultures but are also applicable for cell typing of primary glial or cell line-derived samples. © 2013 Springer Science+Business Media New York.