Fred Hutchinson Cancer Research Center

About: Fred Hutchinson Cancer Research Center is a nonprofit organization based out in Cape Town, South Africa. It is known for research contribution in the topics: Population & Transplantation. The organization has 12322 authors who have published 30954 publications receiving 2288772 citations. The organization is also known as: Fred Hutch & The Hutch.

Challenges to curing primary brain tumours

Abstract: Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour. The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment.

Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo.

Abstract: Eukaryotic translation initiation factor 4E (eIF4E) binds to the mRNA 5* cap and brings the mRNA into a complex with other protein synthesis initiation factors and ribosomes. The activity of mammalian eIF4E is important for the translation of capped mRNAs and is thought to be regulated by two mechanisms. First, eIF4E is sequestered by binding proteins, such as 4EBP1, in quiescent cells. Mitogens induce the release of eIF4E by stimulating the phosphorylation of 4EBP1. Second, mitogens and stresses induce the phosphorylation of eIF4E at Ser 209, increasing the affinity of eIF4E for capped mRNA and for an associated scaffolding protein, eIF4G. We previously showed that a mitogen- and stress-activated kinase, Mnk1, phosphorylates eIF4E in vitro at the physiological site. Here we show that Mnk1 regulates eIF4E phosphorylation in vivo. Mnk1 binds directly to eIF4G and copurifies with eIF4G and eIF4E. We identified activating phosphorylation sites in Mnk1 and developed dominant-negative and activated mutants. Expression of dominant-negative Mnk1 reduces mitogeninduced eIF4E phosphorylation, while expression of activated Mnk1 increases basal eIF4E phosphorylation. Activated mutant Mnk1 also induces extensive phosphorylation of eIF4E in cells overexpressing 4EBP1. This suggests that phosphorylation of eIF4E is catalyzed by Mnk1 or a very similar kinase in cells and is independent of other mitogenic signals that release eIF4E from 4EBP1.

Use of retroviral vectors for gene transfer and expression.

Abstract: Publisher Summary This chapter discusses the use of retroviral vectors for gene transfer and expression Retroviruses have evolved a highly efficient gene transfer capability that provides the basis for one of the most effective gene transfer systems available to date The retroviral vector system has proved useful for the transfer of genes into many cell types, such as hematopoietic cells and other primary cells that are difficult to transduce by using other methods Most attempts to make virus from a particular vector have been straightforward, resulting in high-titer virus carrying the unrearranged vector In some cases, it has proved difficult to generate high-titer virus from vectors carrying specific genes or cDNAs However, the presence of the intron in reverse orientation resulted in aberrant vector transcription and low vector titers Some reports suggest that the titer of retroviral vectors can be dramatically increased by the cocultivation of a vector-producing cell line with a packaging cell line having a different host range However, no more than a 2- to 10-fold increase has been found in titer by using this method, with the disadvantages of increased probability of helper virus generation and vector rearrangement

Non-Hodgkin's Lymphomas

Abstract: Part 1 Lymphomagenesis: Lymphocyte differentiation Adult T-cell leukaemia/Lymphoma - a model of retrovirus-induced lymphomagenesis Burkitt's lymphoma and Epstein-Barr virus-associated lymphoid malignancies - models for lymphomagenesis T(14 18) translocation. Part 2 Methods: Histological and immunohistochemical methods Genotype. Part 3 Nodal Non-Hodgkin's Lymphomas: The normal lymph node - structure and function Histological classification Staging of NHLs Analytical study of the different subtypes of NHLs - clinical, histological and immunohistochemical aspects NHLs in childhood NHLs associated with HIV infection. Part 4 Extra-Nodal Non-Hodgkin's lymphomas: Malignant lymphomas of mucosa-associated lymphoid tissues Primary gastrointestinal NHLs Pathology of gastro-intestinal NHLs Cutaneous lymphomas NHLs of the Mediastinum NHLs of the lung Bone marrow involvement Blood involvement in chronic (mature) B & T lymphoproliferative syndromes Liver involvement Spleen involvement Extra-cranial head-and-neck NHLs Central nervous system involvement NHLs of bone Urogenital localizations. Part 5 Treatment of Non-Hodgkin's Lymphomas: Methodology and problems in the comparison of results Treatment of lowgrade NHLs The role of radiation therapy Treatment of aggressive lymphomas (intermediate and highgrade) Intensive chemoradiotherapy and bone-marrow transplantation Salvage therapy after failure Treatment of NHLs in childhood.