TY  - JOUR
AB  - Metabolic reprogramming is one of the main hallmarks of cancer cells. It refers to the metabolic adaptations of tumor cells in response to nutrient deficiency, microenvironmental insults, and anti-cancer therapies. Metabolic transformation during tumor development plays a critical role in the continued tumor growth and progression and is driven by a complex interplay between the tumor mutational landscape, epigenetic modifications, and microenvironmental influences. Understanding the tumor metabolic vulnerabilities might open novel diagnostic and therapeutic approaches with the potential to improve the efficacy of current tumor treatments. Prostate cancer is a highly heterogeneous disease harboring different mutations and tumor cell phenotypes. While the increase of intra-tumor genetic and epigenetic heterogeneity is associated with tumor progression, less is known about metabolic regulation of prostate cancer cell heterogeneity and plasticity. This review summarizes the central metabolic adaptations in prostate tumors, state-of-the-art technologies for metabolic analysis, and the perspectives for metabolic targeting and diagnostic implications.
AU  - Peitzsch, C.*
AU  - Gorodetska, I.*
AU  - Klusa, D.*
AU  - Shi, Q.*
AU  - Alves, T.C.
AU  - Pantel, K.*
AU  - Dubrovska, A.*
C1  - 67015
C2  - 53379
SP  - 94-119
TI  - Metabolic regulation of prostate cancer heterogeneity and plasticity.
JO  - Semin. Cancer Biol.
VL  - 82
PY  - 2022
SN  - 1044-579X
ER  - 

TY  - JOUR
AB  - Deregulations promoting constitutive activation of canonical and non-canonical NF-κB signaling are a common feature of many lymphoid malignancies. Due to their cellular origin and the pivotal role of NF-κB for the normal function of B lymphocytes, B-cell malignancies are particularly prone to genetic aberrations that affect the pathway. Key positive regulators of NF-κB signaling can act as oncogenes that are often prone to chromosomal translocation, amplifications or activating mutations. Negative regulators of NF-κB have tumor suppressor functions and are frequently inactivated either by genomic deletions or point mutations. Whereas some aberrations are found in a variety of different lymphoid malignancies, some oncogenic alterations are very restricted to distinct lymphoma subsets, reflecting the clonal and cellular origin of specific lymphoma entities. NF-κB activation in many lymphoma cells is also driven by the microenvironment or chronic signaling that does not rely on genetic alterations. A number of drugs that target the NF-κB pathway are in preclinical or clinical development, revealing that there will be new options for therapies in the future. Since each lymphoma entity utilizes distinct mechanisms to activate NF-κB, a major challenge is to elucidate the exact pathological processes in order to faithfully predict clinical responses to the different therapeutic approaches.
AU  - Krappmann, D.
AU  - Vincendeau, M.
C1  - 48743
C2  - 41305
CY  - London
SP  - 3-14
TI  - Mechanisms of NF-κB deregulation in lymphoid malignancies.
JO  - Semin. Cancer Biol.
VL  - 39
PB  - Academic Press Ltd- Elsevier Science Ltd
PY  - 2016
SN  - 1044-579X
ER  - 

TY  - JOUR
AB  - For several reasons Burkitt's lymphoma (BL) has become a paradigm in cancer research: for its particular geographical distribution, the presence of Epstein-Barr virus (EBV) in the cases in high incidence areas, and for the activation of the proto-oncogene c-myc by chromosomal translocation in one of the immunoglobulin gene loci. As c-MYC activates both, proliferation and apoptosis, at least two events have to cooperate in lymphomagenesis: Activation of c-MYC and a shift in the balance from apoptosis towards survival. Antigenic and/or polyclonal stimulation of the B cell receptor, genetic instability imposed by activation induced deaminase (AID), as well as the viral gene products EBNA1 and several small non-coding non-polyadenylated RNAs are the main factors suspected to play an important role in the pathogenesis of BL Despite intensive research, the role of the virus has remained largely elusive in the past decades, but the discovery of two viral microRNA clusters that are expressed in EBV associated tumors including BL has raised new hopes and expectations that EBV is going to reveal its mystery. This review focuses on the interplay between cellular and viral factors and puts special emphasis on mouse models and experimental cell culture systems that address these points.
AU  - Bornkamm, G.W.
C1  - 479
C2  - 27086
SP  - 351-365
TI  - Epstein-Barr virus and its role in the pathogenesis of Burkitt's lymphoma: An unresolved issue.
JO  - Semin. Cancer Biol.
VL  - 19
IS  - 6
PB  - Elsevier
PY  - 2009
SN  - 1044-579X
ER  - 

TY  - JOUR
AB  - Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The 'mini-EBVs', for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might include the genetic identification and characterization of viral proteins involved in the modulation of the immune response and, in particular, immune evasion. Recombinant viral strains are already being used experimentally for the expansion of T cells in vitro prior to in vivo cellular therapy and have been proposed as potential prophylactic vaccines.
AU  - Delecluse, H.-J.*
AU  - Feederle, R.*
AU  - Behrends, U.
AU  - Mautner, J.
C1  - 3033
C2  - 25924
SP  - 409-415
TI  - Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus.
JO  - Semin. Cancer Biol.
VL  - 18
IS  - 6
PB  - Academic Press
PY  - 2008
SN  - 1044-579X
ER  - 

TY  - JOUR
AB  - The clear evidence that tumor-infiltrating lymphocytes with anti-tumor activity exist in situ raises the question why renal cell carcinomas (RCCs) progress in vivo. A complex array of factors and pathways has been identified that impinges on innate and adaptive effector cells thereby inhibiting their activity against RCCs. The current picture of suppressive mechanisms that contribute to the failure of the immune system to control RCCs is reviewed here. Understanding these complex host-tumor interactions has broad implications for successful application of cytokine therapy and other forms of immunotherapy for RCC.
AU  - Frankenberger, B.
AU  - Nößner, E.
AU  - Schendel, D.J.
C1  - 570
C2  - 24768
SP  - 330-343
TI  - Immune suppression in renal cell carcinoma.
JO  - Semin. Cancer Biol.
VL  - 17
IS  - 4
PB  - Saunders
PY  - 2007
SN  - 1044-579X
ER  - 

TY  - JOUR
AU  - Bohlander, S.K.
C1  - 5282
C2  - 23300
SP  - 162-174
TI  - ETV6: A versatile player in leukemogenesis.
JO  - Semin. Cancer Biol.
VL  - 15
PY  - 2005
SN  - 1044-579X
ER  - 

TY  - JOUR
AU  - Ensoli, B.*
AU  - Stürzl, M.
AU  - Monini, P.*
C1  - 21560
C2  - 19685
SP  - 367-381
TI  - Cytokine-mediated growth promotion of Kaposi's sarcoma and primary effuaion lymphoma.
JO  - Semin. Cancer Biol.
VL  - 10
PY  - 2000
SN  - 1044-579X
ER  -