TY  - JOUR
AB  - To establish strategies for immunotherapy of B-cell lymphoma, it is mandatory to gain deeper insights into the mechanisms of tumor immune escape. In a mouse model of endogenously arising lymphoma, we investigated the impact of IL-10 on the regulation of antitumor responses. Despite progressive functional impairment of NK cells and lack of IFN-γ in the tumor milieu, we found an augmented fraction of T helper type 1 (Th1) cells, which continued to express IFN-γ but also upregulated IL-10 during disease development. Using a lymphoma microenvironment in vitro, we showed that Th1 cells were converted to Foxp3-negative T regulatory type 1 (Tr1) cells, which coexpressed IFN-γ and IL-10 and upregulated PD-1. This differentiation required pre-existing IL-10, which was primarily provided by malignant B cells and dendritic cells. IFN-γ only declined in cells with the uppermost PD-1 levels. Importantly, antibody-mediated IL-10 ablation in vivo improved effector cell functions and significantly suppressed tumor development. While the contribution of IL-10 to cancer immune escape has been controversially discussed in the past, we show that IL-10 suppresses ongoing, potentially protective immune responses in lymphoma and might be a target for immunotherapy.
AU  - Ma, Y.
AU  - Bauer, V.
AU  - Riedel, T.
AU  - Ahmetlic, F.
AU  - Hömberg, N.
AU  - Hofer, T.P.
AU  - Röcken, M.*
AU  - Mocikat, R.
C1  - 61189
C2  - 50009
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
SP  - 110-116
TI  - Interleukin-10 counteracts T-helper type 1 responses in B-cell lymphoma and is a target for tumor immunotherapy.
JO  - Cancer Lett.
VL  - 503
PB  - Elsevier Ireland Ltd
PY  - 2021
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Tumor-derived extracellular vesicles (TEVs) released from various tumor cell types comprise endosome-derived exosomes and microvesicles (MVs), which originate from plasma membrane budding. TEVs incorporate a myriad of biomolecules such as proteins, DNAs, metabolites and microRNAs, which can be transferred from cell-to-cell. Besides their role in the disposal of biomolecules, TEVs serve to orchestrate fundamental processes of normal and malignant development, including breast cancer (BC). As such, TEVs are important constituents of the tumor microenvironment (TME) that act as communication shuttles through transduction of encapsulated molecular cargos from a parent to a recipient cell and through direct interaction with target cells. Emerging evidence suggests that TEVs support BC development and disease progression by fostering invasion, angiogenesis, premetastatic niche preparation, escape from immune surveillance, and induction of resistance to treatment. Although there is a long way to go in order to translate the current knowledge into actual clinical applications, TEVs represent promising candidates for diagnostic biomarkers, therapeutic carriers and targets. In the present review, we will summarize the current knowledge on TEVs in BC.
AU  - Wang, H.X.*
AU  - Gires, O.
C1  - 56396
C2  - 47038
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
SP  - 54-64
TI  - Tumor-derived extracellular vesicles in breast cancer: From bench to bedside.
JO  - Cancer Lett.
VL  - 460
PB  - Elsevier Ireland Ltd
PY  - 2019
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy. Simultaneously inhibiting glutaminolysis and either beta oxidation with trimetazidine or autophagy with chloroquine both induced cancer cell death. Here we identified metabolic escape mechanisms contributing to cancer cell survival under treatment and we suggest potentially translational strategy for combined cancer therapy, given that chloroquine is an FDA approved drug. Our findings are first to show efficiency of combined inhibition of glutaminolysis and beta oxidation as potential anti-cancer strategy as well as add to the evidence that combined inhibition of glutaminolysis and autophagy may be effective in glutamine-addicted cancers.
AU  - Halama, A.*
AU  - Kulinski, M.*
AU  - Dib, S.S.*
AU  - Zaghlool, S.B.*
AU  - Siveen, K.S.*
AU  - Iskandarani, A.*
AU  - Zierer, J.*
AU  - Prabhu, K.S.*
AU  - Satheesh, N.J.*
AU  - Bhagwat, A.M.*
AU  - Uddin, S.*
AU  - Kastenmüller, G.
AU  - Elemento, O.*
AU  - Gross, S.S.*
AU  - Suhre, K.*
C1  - 53550
C2  - 44893
CY  - Po Box 211, 1000 Ae Amsterdam, Netherlands
SP  - 133-147
TI  - Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis.
JO  - Cancer Lett.
VL  - 430
PB  - Elsevier Science Bv
PY  - 2018
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM D-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation. While hyperglycemia (25 mM D-glucose) did not impact the mesenchymal phenotype of Pancl cells, CSC-properties were aggravated exemplified by increased Nanog expression and Nanog-dependent formation of holo- and meroclones. In H6c7-kras cells, high glucose increased secretion of Transforming-Growth-Factor-betal (TGF-beta 1) as well as TGF-beta 1 signaling, and in a TGF-beta 1-dependent manner reduced E-cadherin expression, increased Nestin expression and number of meroclones. Finally, reduced E-cadherin expression was detected in pancreatic ducts of hyperglycemic but not normoglycemic mice. These data suggest that hyperglycemia promotes the acquisition of mesenchymal and CSC-properties in PDEC by activating TGF-beta signaling and might explain how T2DM facilitates pancreatic tumorigenesis. (C) 2017 Elsevier B.V. All rights reserved.
AU  - Rahn, S.*
AU  - Zimmermann, V.*
AU  - Viol, F.*
AU  - Stemmer, K.
AU  - Peters, L.*
AU  - Lenk, L.*
AU  - Ungefroren, H.*
AU  - Saur, D.*
AU  - Schäfer, H.*
AU  - Helm, O.*
AU  - Sebens, S.*
C1  - 52513
C2  - 44153
CY  - Clare
SP  - 129-150
TI  - Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells.
JO  - Cancer Lett.
VL  - 415
PB  - Elsevier Ireland Ltd
PY  - 2018
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC.
AU  - Hess J.
AU  - Unger, K.
AU  - Orth, M.*
AU  - Schötz, U.*
AU  - Schüttrumpf, L.
AU  - Zangen, V.
AU  - Gimenez-Aznar, I.
AU  - Michna, A.
AU  - Schneider, L.
AU  - Stamp, R.
AU  - Selmansberger, M.
AU  - Braselmann, H.
AU  - Hieber, L.
AU  - Drexler, G.A.*
AU  - Kuger, S.
AU  - Klein, D.*
AU  - Jendrossek, V.*
AU  - Friedl, A.A.
AU  - Belka, C.
AU  - Zitzelsberger, H.
AU  - Lauber, K.
C1  - 50077
C2  - 42185
CY  - Clare
SP  - 87-99
TI  - Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.
JO  - Cancer Lett.
VL  - 386
PB  - Elsevier Ireland Ltd
PY  - 2017
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - The inhibition of heat shock protein 90 (Hsp90) is a promising strategy to increase the radiosensitivity of tumor cells. However, Hsp90 inhibition induces the expression of Hsp70 which is a prominent cytoprotective protein. Therefore, dual targeting of Hsp70 and Hsp90 might be beneficial to increase the radiosensitivity of tumor cells. Hsp70 inhibiting peptide aptamers have been shown to increase the sensitivity of tumor cells to apoptosis induced by different anticancer drugs. Herein, we studied the radiosensitizing activity of the Hsp70 inhibiting peptide aptamer A17 in combination with the Hsp90 inhibitor NVP-AUY922. Whereas A17 significantly increased apoptosis induction by NVP-AUY922 it did not significantly affect the radiosensitivity of human lung and breast cancer cells. However, Hsp70 inhibition by the aptamer A17 potentiated the radiosensitizing effects of the Hsp90 inhibitor NVP-AUY922. Mechanistically we speculate that an increased number of DNA double strand breaks and an enhanced G2/M arrest might be responsible for the increased radiosensitization in A17 expressing tumor cells. Therefore, the simultaneous inhibition of Hsp90 and Hsp70 combined with radiotherapy might provide a promising anti-cancer strategy.
AU  - Schilling, D.
AU  - Garrido, C.*
AU  - Combs, S.E.
AU  - Multhoff, G.
C1  - 50457
C2  - 42473
SP  - 146-152
TI  - The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition.
JO  - Cancer Lett.
VL  - 390
PY  - 2017
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Excessive matrix production by pancreatic stellate cells promotes local growth and metastasis of pancreatic ductal adenocarcinoma and provides a barrier for drug delivery. Collagen type V is a fibrillar, regulatory collagen up-regulated in the stroma of different malignant tumors. Here we show that collagen type V is expressed by pancreatic stellate cells in the stroma of pancreatic ductal adenocarcinoma and affects the malignant phenotype of various pancreatic cancer cell lines by promoting adhesion, migration and viability, also after treatment with chemotherapeutic drugs. Pharmacological and antibody-mediated inhibition of β1-integrin signaling abolishes collagen type V-induced effects on pancreatic cancer cells. Ablation of collagen type V secretion of pancreatic stellate cells by siRNA reduces invasion and proliferation of pancreatic cancer cells and tube formation of endothelial cells. Moreover, stable knock-down of collagen type V in pancreatic stellate cells reduces metastasis formation and angiogenesis in an orthotopic mouse model of ductal adenocarcinoma. In conclusion, paracrine loops involving cancer and stromal elements and mediated by collagen type V promote the malignant phenotype of pancreatic ductal adenocarcinoma and underline the relevance of epithelial-stromal interactions in the progression of this aggressive neoplasm.
AU  - Berchtold, S.*
AU  - Grünwald, B.*
AU  - Krüger, A.*
AU  - Reithmeier, A.*
AU  - Hähl, T.*
AU  - Cheng, T.*
AU  - Feuchtinger, A.
AU  - Born, D.*
AU  - Erkan, M.*
AU  - Kleeff, J.*
AU  - Esposito, I.*
C1  - 42895
C2  - 35811
CY  - Clare
SP  - 721-732
TI  - Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma.
JO  - Cancer Lett.
VL  - 356
IS  - 2
PB  - Elsevier Ireland Ltd
PY  - 2015
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Despite enormous progress in radiation technologies (high precision image-guided irradiation, proton irradiation, heavy ion irradiation), and radiotherapeutic concepts (hypofractionated irradiation schemes), the clinical outcome of radiotherapy in locally advanced and metastasized tumors and in hypoxic tumors which are radiation-resistant remain unsatisfactory. Given their key influence on a number of biological and immunological parameters, this article considers the influence of irradiation-induced stress proteins on radiation-induced immunomodulation. Depending on its location, the major stress-inducible Heat shock protein 70 (Hsp70) has been found to fulfill multiple roles. On the one hand, increased intracellular Hsp70 levels have been found to play a key role in the recovery from stress such as radio(chemo)therapy, and on the other hand extracellular Hsp70 proteins are potent stimulators of the innate immune system and mediators of anti-tumor immunity. Furthermore, if loaded with tumor-derived peptides, members of the Heat Shock Protein 70 (HSP70) and 90 (HSP90) families can stimulate the adaptive immune system via antigen cross-presentation. An irradiation-induced enhancement of the selective expression of a membrane form of Hsp70 on the surface of tumor cells which can act as a recognition structure for activated NK cells might have significant clinical relevance, in that the outcome of irradiation therapy for advanced tumors could be improved by combining it with cell-based and other immunotherapies that target this membrane form of Hsp70.
AU  - Multhoff, G.
AU  - Pockley, A.G.*
AU  - Schmid, T.E.*
AU  - Schilling, D.*
C1  - 43298
C2  - 36556
SP  - 179-184
TI  - The role of Heat shock protein 70 (Hsp70) in radiation-induced immunomodulation.
JO  - Cancer Lett.
VL  - 368
IS  - 2
PY  - 2015
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Considerable progress has recently been achieved in the understanding of molecular mechanisms involved in cellular radiation responses and radiation mediated microenvironmental communication. In line with that, it has become more and more obvious that X-irradiation causes distinct immunological effects ranging from anti-inflammatory activities if applied at low (<1Gy) doses to harmful inflammatory side effects, radiation-induced immune modulation or induction of anti-tumour immune responses at higher doses. Moreover, experimental and clinical evidences indicate that these effects not only originate from direct nuclear damage but also include non-(DNA) targeted mechanisms including bystander, out of field distant bystander (abscopal) effects and genomic instability. The purpose of the present review is to elucidate immune responses that are initiated or affected by ionizing radiation, with a special emphasis on anti-inflammatory and abscopal effects and the induction of stress-induced anti-tumour immunity.
AU  - Rödel, F.*
AU  - Frey, B.*
AU  - Multhoff, G.*
AU  - Gaipl, U.
C1  - 28099
C2  - 32933
CY  - Clare
SP  - 105-113
TI  - Contribution of the immune system to bystander and non-targeted effects of ionizing radiation.
JO  - Cancer Lett.
VL  - 356
IS  - 1
PB  - Elsevier Ireland
PY  - 2015
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Elevated levels of heat shock proteins (Hsps) contribute to tumor cell survival and mediate protection against radiation-induced cell death. Hsp90 inhibitors are promising radiosensitizers but also activate heat shock factor 1 (HSF1) and thereby induce the synthesis of cytoprotective Hsp70. In this study the heat shock response inhibitor NZ28 either alone or in combination with the Hsp90 inhibitor NVP-AUY922 was investigated for radiosensitizing effects, alterations in cell cycle distribution and effects on migratory/invasive capacity of radioresistant tumor cells. NZ28 reduced the constitutive and NVP-AUY922-induced Hsp70 expression by inhibition of the HSF1 activity and inhibited migration and invasion in human lung and breast tumor cells. Treatment of tumor cells with NZ28 significantly increased their radiation response. One possible mechanism might be a decrease of the radioresistant S-phase. When combined with the Hsp90 inhibitor NVP-AUY922 the concentration of NZ28 could be significantly reduced (1/10(th) to 1/20(th)) to achieve the same radiosensitization. Our results demonstrate that a dual targeting of Hsp70 and Hsp90 with NZ28 and NVP-AUY922 potentiates the radiation response of tumor cells that are otherwise resistant to ionizing radiation.
AU  - Schilling, D.
AU  - Kühnel, A.*
AU  - Konrad, S.*
AU  - Tetzlaff, F.*
AU  - Bayer, C.*
AU  - Yaglom, J.*
AU  - Multhoff, G.
C1  - 43519
C2  - 36557
CY  - Clare
SP  - 294-301
TI  - Sensitizing tumor cells to radiation by targeting the heat shock response.
JO  - Cancer Lett.
VL  - 360
IS  - 2
PB  - Elsevier Ireland Ltd
PY  - 2015
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Whole exome sequencing (WES) provides a powerful tool for medical genetic research. Several dozens of WES studies involving patients with hereditary cancer syndromes have already been reported. WES led to breakthrough in understanding of the genetic basis of some exceptionally rare syndromes; for example, identification of germ-line SMARCA4 mutations in patients with hypercalcemic small cell carcinomas indeed explains a noticeable share of familial aggregation of this disease. However, studies on common cancer types turned out to be more difficult. In particular, there is almost a dozen of reports describing WES analysis of breast cancer patients, but none of them yet succeeded to reveal a gene responsible for the significant share of missing heritability. Virtually all components of WES studies require substantial improvement, e.g. technical performance of WES, interpretation of WES results, mode of patient selection, etc. Most of contemporary investigations focus on genes with autosomal dominant mechanism of inheritance; however, recessive and oligogenic models of transmission of cancer susceptibility also need to be considered. It is expected that the list of medically relevant tumor-predisposing genes will be rapidly expanding in the next few years.
AU  - Sokolenko, A.P.*
AU  - Suspitsin, E.N.*
AU  - Kuligina, E.S.*
AU  - Bizin, I.V.*
AU  - Frishman, D.
AU  - Imyanitov, E.N.*
C1  - 46973
C2  - 39097
SP  - 274-288
TI  - Identification of novel hereditary cancer genes by whole exome sequencing.
JO  - Cancer Lett.
VL  - 369
IS  - 2
PY  - 2015
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Transketolase-like protein 1 (TKTL1) is a member of the family of transketolase enzymes of which the founder member transketolase (TKT) is known to play a central role in the non-oxidative part of the pentose phosphate pathway. According to several publications TKTL1 is the only family member, whose expression is substantially de-regulated in a variety of solid tumours. Over-expression of TKTL1 correlates with poor prognosis of cancer patients and TKTL1 itself represents a potential therapeutic target owing to its possible involvement in the regulation of the proliferation and metabolism of cancer cells. We show that exogenously expressed TKTL1 provides HEK293 cells with moderate growth advantages under standard culture conditions, while protecting cells from growth factor withdrawal-induced apoptosis. Importantly, we identified TKTL1 with the JFC12T10 antibody as a 65kDa protein, which was however absent in most tumour cell lines tested. Primary head and neck squamous cell carcinomas of various localisations were characterised by a focal pattern with single cells strongly expressing TKTL1, rather than by a homogeneous expression pattern within the tumour mass.
AU  - Hartmannsberger, D.*
AU  - Mack, B.*
AU  - Eggert, C.*
AU  - Denzel, S.
AU  - Stepp, H.*
AU  - Betz, C.S.*
AU  - Gires, O.
C1  - 5971
C2  - 27677
CY  - Clare, Ireland
SP  - 20-29
TI  - Transketolase-like protein 1 confers resistance to serum withdrawal in vitro.
JO  - Cancer Lett.
VL  - 300
IS  - 1
PB  - Elsevier
PY  - 2011
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - The majority of patients tolerate radiotherapy well, but some of them suffer from severe side effects. To find genes possibly predictive for radiosensitivity, mRNA profiles were generated before and 6h after in vitro irradiation with 5Gy. We analyzed lymphocytes from four head and neck and eight breast cancer patients with strong acute radiation toxicity and from 12 matching normal reacting patients in a blind study. Expression was also measured in lymphocyte subpopulations and Epstein-Barr transformed lymphocytes. Radiation response in whole lymphocyte populations was most similar to that of B cells. In peripheral blood lymphocytes of all patients; 153 genes were identified which were statistically significantly altered by a fold change of more than 50% by irradiation. The signatures of radio-responsive genes differed tremendously between primary and transformed cells. Pathway analysis revealed genes involved in p53 signalling, cell cycle control and apoptosis in response to radiation in primary lymphocytes. In these cells, a set of 67 radiation-induced genes was identified capable of differentiating between severe radiosensitive and normal reacting patients. More than one third of such classifying genes belong to the group of apoptosis or cell cycle regulating genes. The classifying potential of the expression signature has now to be validated in further patient cohorts.
AU  - Mayer, C.*
AU  - Popanda, O.*
AU  - Greve, B.*
AU  - Fritz, E.*
AU  - Illig, T.
AU  - Eckardt-Schupp, F.
AU  - Gomolka, M.*
AU  - Benner, A.*
AU  - Schmezer, P.*
C1  - 6282
C2  - 28351
SP  - 20-28
TI  - A radiation-induced gene expression signature as a tool to predict acute radiotherapy-induced adverse side effects.
JO  - Cancer Lett.
VL  - 302
IS  - 1
PB  - Elsevier
PY  - 2011
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Hybrids generated from tumor cells and dendritic cells (DC) have been proposed as tools for treating malignant disease. Here, we study the underlying principles and the feasibility for the adjuvant therapy of human B cell chronic-lymphocytic leukemia (B-CLL). CLL cells and allogeneic DC were only mixed or additionally fused. Using a combination of FACS and fluorescence microscopic analyses, we show that DC–CLL hybrids can be successfully generated. However, fusion frequencies have to be critically evaluated because the number of fused cells is overestimated when based on FACS analyses alone. The capability of activating patients' PBMC was examined by measuring cytokine secretion in co-culture assays. We made a systematic comparison of the immunostimulatory capacities of different stimulator cell populations, including DC–CLL fusion samples, unfused mixtures of DC and CLL cells as well as DC or tumor cells alone. Surprisingly, even unfused mixtures had a pronounced tumor-directed immunostimulatory effect. This could be explained by the capture of antigens from surrounding leukemia cells by DC during co-cultivation. Although fusion frequencies were low, PBMC stimulation was significantly more effective when the mixtures were subjected to cell fusion. The most potent stimulus was provided by DC–CLL fusion samples derived from mature DC, probably due to their enhanced costimulatory capacity. In summary, DC–tumor cell hybrids might be feasible in the treatment of B-CLL. It should be considered that FACS analysis is not sufficient to assess fusion frequencies and that interactions between unfused DC and CLL cells also result in PBMC activation.
AU  - Allgeier, T.
AU  - Garhammer, S.
AU  - Nößner, E.
AU  - Wahl, U.
AU  - Kronenberger, K.
AU  - Dreyling, M.*
AU  - Hallek, M.*
AU  - Mocikat, R.
C1  - 2836
C2  - 24384
SP  - 275-283
TI  - Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia.
JO  - Cancer Lett.
VL  - 245
IS  - 1-2
PB  - Elsevier
PY  - 2007
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - The epithelial cell adhesion molecule, EpCAM, is a transmembrane glycoprotein associated with both benign and malignant proliferation. In cancer cells, expression levels of this tumour-associated antigen correlate positively with the grade of dysplasia and are also a negative prognostic factor for breast cancer patients. De novo expression of EpCAM resulted in the rapid upregulation of the proto-oncogene c-Myc along with enhanced cell proliferation and metabolism. Here, we analyzed the effects of EpCAM onto the proteome of epithelial cells. The epidermal fatty acid binding protein, E-FABP, was identified as a new EpCAM-regulated protein. E-FABP is a major target of c-Myc and was rapidly upregulated upon induction of EpCAM. Additionally, E-FABP levels correlated with the amount of EpCAM in permanent squamous cell carcinoma lines and in vivo in primary head and neck carcinomas. Taken together, these results provide further evidence for the direct involvement of EpCAM in signalling processes, gene regulation, and cellular metabolism supporting its important role in tumour biology.
AU  - Münz, M.
AU  - Zeidler, R.*
AU  - Gires, O.
C1  - 4307
C2  - 23058
SP  - 151-157
TI  - The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP.
JO  - Cancer Lett.
VL  - 225
IS  - 1
PY  - 2005
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - The involvement of SODD/BAG-4 was studied in TNFR1 signaling, using SODD/BAG-4- overexpressing HeLa cells as a cellular model. Stable transfection of a SODD/BAG-4 cDNA leads to increased levels of the full-length 70-kDa protein and additional C-terminal fragments as well as altered expression of BAG-1. Concomitantly, the protein amounts of both the TNFR1 and, unexpectedly, the CD95 receptors are elevated. These biochemical changes are paralleled and confirmed by a reduced cellular sensitivity to treatment with extracellular TNFα and CD95 ligand. Moreover, ATP depletion by oligomycin is less toxic in SODD/BAG-4 overexpressing clones. The radiosensitivity is reduced in some, but not in all of these clones. Our results indicate that SODD/BAG-4 is not only a silencer of TNFR1 but also a modulator of CD95 activity, regulating the balance of both death-promoting and -depressing signals.
AU  - Eichholtz-Wirth, H.
AU  - Fritz, E.
AU  - Wolz, L.
C1  - 10314
C2  - 21456
SP  - 81-89
TI  - Overexpression of the 'silencer of death domain', SODD/BAG-4, modulates both TNFR1- and CD95-dependent cell death pathways.
JO  - Cancer Lett.
VL  - 194
IS  - 1
PY  - 2003
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - The tissue-specific glycosylation of the carcinoma (CA)-associated antigen epithelial cell adhesion molecule (EpCAM) was studied in 60 patients suffering from head and neck CAs, and 26 pairs of autologous healthy thyroid and CA biopsies. EpCAM was glycosylated in all tumor samples in which its expression was detectable (73%). Additionally, in 80.7% of patients, tumor-derived EpCAM was heavily glycosylated while EpCAM derived from autologous thyroid was not (76.2%) or weakly (23.8%). Four cases showed a similar glycosylation pattern (15.3%) and one case displayed a reverse pattern (3.8%). Additionally, the expression and glycosylation of EpCAM were assessed in tumor adjacent and distant tissue. EpCAM was glycosylated in tumor-adjacent while it was not or only weakly expressed in tumor distant tissue where it was unglycosylated. Thus, EpCAM is differentially glycosylated in healthy tissue and tumor cells of the head and neck area.
AU  - Pauli, C.*
AU  - Münz, M.*
AU  - Kieu, C.*
AU  - Mack, B.*
AU  - Breinl, P.*
AU  - Wollenberg, B.*
AU  - Lang, S.*
AU  - Zeidler, R.*
AU  - Gires, O.
C1  - 2610
C2  - 22028
SP  - 25-32
TI  - Tumor-specific glycosylation of the carcinoma-associated epithelial cell adhesion molecule EpCAM in head and neck carcinomas.
JO  - Cancer Lett.
VL  - 193
IS  - 1
PY  - 2003
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - The level of activity of O6-alkylguanine-DNA-alkyltransferase (AGT), a DNA repair enzyme, in blood lymphocytes may be a marker of susceptibility to lung cancer. We measured the AGT activity level, expressed as pmoles of repaired bases/mg protein, in leukocytes of 153 lung cancer cases (of whom 80 were never smokers) and 106 controls (76 never smokers) enrolled in eight centres from seven countries. Subjects were interviewed with respect to active smoking and exposure to environmental tobacco smoke (ETS). Among never smokers, the odds ratios (ORs) of lung cancer were 1.3 (95% confidence interval 0.5–3.9), 1.5 (0.6–4.1) and 1.4 (0.5–3.8) in quartiles of decreasing AGT activity level, as compared to the upper quartile (P value of test for linear trend 0.6). Corresponding ORs among smokers were 3.4 (0.9–13), 2.0 (0.5–8.3) and 0.4 (0.1–1.6) (P value of test for linear trend 0.4). No interaction was suggested between AGT activity level and either cumulative smoking or exposure to ETS. Reduced AGT activity was not clearly associated with increased lung cancer risk in either smokers or non-smokers. However, the small size of our study argues for a prudent interpretation of our results.
AU  - Boffetta, P.*
AU  - Nyberg, F.*
AU  - Mukeria, A.*
AU  - Benhamou, S.*
AU  - Constantinescu, V.*
AU  - Batura-Gabryel, H.*
AU  - Brüske, I.
AU  - Schmid, G.*
AU  - Simonato, L.*
AU  - Pelkonen, P.*
AU  - Hall, J.*
C1  - 22063
C2  - 20697
SP  - 33-39
TI  - O6-Alkylguanine-DNA-alkyltransferase activity in peripheral leukocytes, smoking and risk of lung cancer.
JO  - Cancer Lett.
VL  - 180
IS  - 1
PY  - 2002
SN  - 0304-3835
ER  - 

TY  - JOUR
AB  - Thiourea (TU) fails to enhance the incidence of foci deficient in adenosine-5'-trisphosphatase (ATPase) either by initiation or by promotion in a rat liver foci bioassay. To weanling female Sprague-Dawley rats, 3 x 200 or 3 x 500 mg/kg body wt of TU, respectively, were applied for initiation. One week later Clophen A 50, a technical mixture of polychlorinated biphenyls (PCBs) 2 x 10 mg/kg body wt were given twice weekly as promoting agent for 11 weeks. For promotion 0.2% of TU was administered with the drinking water for 51 days to rats of both sexes, and 0.1% and 0.05% of TU, respectively, for 70 days to females after initiation with 1 x 8 mg/kg body wt of diethylnitrosamine (DEN).
AU  - Oesterle, D.
AU  - Deml, E.
C1  - 42290
C2  - 36177
SP  - 245-249
TI  - Lack of initiating and promoting activity of thiourea in rat liver foci bioassay.
JO  - Cancer Lett.
VL  - 41
IS  - 3
PY  - 1988
SN  - 0304-3835
ER  -