TY  - JOUR
AB  - BACKGROUND/AIM: Rhenium(I)-diselenoether (Re-diSe) is a compound combining a rhenium tricarbonyl(I) core with a diselenide ligand. A high dose of 60 mg/kg had a pro-tumor effect in a previous study, in non-immune deficient 4T1 tumor-bearing mice, while doses of 1 and 10 mg/kg did not affect tumor growth, after repeated oral administrations. This study aimed to examine the tumor effects of a lower dose of 0.1 mg/kg with the same experimental design and to assay plasma Re and Se concentrations. MATERIALS AND METHODS: Syngenic BALB/cByJ (JAX) mice were orthotopically inoculated with 4T1 mammary breast cancer cells. Re-diSe was daily administered orally for 23 days at doses of 0.1, 1, and 10 mg/kg, whereas controls received no treatment. Tumor and mice weights were measured at the end of the experiment. Plasma Re and Se concentrations were assayed by an inductively coupled plasma sector field mass spectrometry instrument (ICP-sf-MS). RESULTS: The weight of the tumors did not vary in treated versus non-treated mice. The limit of detection (LOD) of Re was 0.34 nmol/l. Plasma Re concentrations were 14±20 nmol/l at doses of 0.1 mg/kg, and increased at higher doses, up to 792±167 nmol/l at doses of 10 mg/kg. Plasma Se concentrations were significantly increased in mice treated with the dose of 0.1 mg/kg (4,262±1,511 nmol/l) versus controls (1,262±888 nmol/l), but not from 0.1 to 1 mg/kg, nor from 1 to 10 mg/kg. CONCLUSION: The 0.1 mg/kg dose of Re-diSe resulted in detectable plasma Re concentrations and significantly increased plasma Se concentrations. In the future, doses as low as 0.1 mg/kg of Re-diSe will be tested, exploring its potential immune interest as a metronomic schedule of treatment, but in mouse models that readily develop extensive metastatic disease.
AU  - Collery, P.*
AU  - Michalke, B.
AU  - Lucio, M.
AU  - Varlet, D.*
AU  - Guigonis, J.M.*
AU  - Scimeca, J.C.*
AU  - Schmid-Antomarchi, H.*
AU  - Schmid-Alliana, A.*
C1  - 67512
C2  - 54077
CY  - Editorial Office 1st Km Kapandritiou-kalamou Rd Kapandriti, Po Box 22, Athens 19014, Greece
SP  - 1017-1023
TI  - Plasma rhenium and selenium concentrations after repeated daily oral administration of Rhenium(I)-diselenoether in 4T1 breast tumor-bearing mice.
JO  - Anticancer Res.
VL  - 43
IS  - 3
PB  - Int Inst Anticancer Research
PY  - 2023
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - BACKGROUND/AIM: Surgical resection for soft tissue sarcomas (STSs) is the gold standard for a curative oncologic therapy in combination with neoadjuvant or adjuvant radiation therapy (NRT/ART). The aim of this study was to determine prognostic factors influencing the survival of patients with STS undergoing NRT or ART considering various parameters in a retrospective, single-centre analysis over 15 years. PATIENTS AND METHODS: We included 119 patients (male 59) and the median follow-up period was 69 months (4-197). The patients received NRT (n=64) or ART (n=55). We recorded the histopathologic subtype of STS, tumour grade, localization, tumour margins, complications, survival, local recurrence, and metastases. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The overall survival rate was 68.9% at 5 years. The localization (epifascial/subfascial), resection margin and type of radiation therapy (NRT/ART) had no significant impact on survival. Tumour grade, tumour size, local recurrence and metastases were significantly correlated with patient survival (p<0.05). Local recurrence was significantly higher in patients with ART (p=0.044). CONCLUSION: Tumour grade and tumour size were independently associated with disease-specific survival, and patients with local recurrence and metastases had lower survival rates.
AU  - Muehlhofer, H.M.L.*
AU  - Schlossmacher, B.*
AU  - Lenze, U.*
AU  - Lenze, F.*
AU  - Burgkart, R.*
AU  - Gersing, A.S.*
AU  - Peeken, J.C.
AU  - Combs, S.E.
AU  - von Eisenhart-Rothe, R.*
AU  - Knebel, C.*
C1  - 60941
C2  - 49997
CY  - Editorial Office 1st Km Kapandritiou-kalamou Rd Kapandriti, Po Box 22, Athens 19014, Greece
SP  - 359-368
TI  - Oncological outcome and prognostic factors of surgery for soft tissue sarcoma after neoadjuvant or adjuvant radiation therapy: A retrospective analysis over 15 years.
JO  - Anticancer Res.
VL  - 41
IS  - 1
PB  - Int Inst Anticancer Research
PY  - 2021
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - Background/Aim: We evaluated the influence of smoking on head and neck squamous cell carcinomas (HNSCC), which are in their majority tobacco-driven. Tobacco smoke is expected to influence the expression of ABCG2-transporters involved in multidrug resistance. The aim of the study was to evaluate the effect of cigarette smoke condensate (CSC) on ABCG2 expression on HNSCC cells, to demonstrate the adverse effects of cigarette smoke during anticancer treatment in vitro and to assess the prevalence of ABCG2 expression in HNSCC. Materials and methods: HNSCC cell lines were treated with CSC and basal and induced ABCG2 expression was examined. The impact of CSC on cellular viability/proliferation during cytotoxic drug treatment was also evaluated. ABCG2 expression levels in HNSCC were correlated with the smoking history of patients. Results: HNSCC cells showed low basal ABCG2 expression. CSC treatment resulted in a threefold increase in the expression of ABCG2 and in resistance to cisplatin. Tumor samples of never smokers showed significantly higher ABCG2 expression compared to ever smokers. ABCG2 expression correlated with pack years of cigarette consumption. Conclusion: Tobacco consumption is linked to an inducible and increased ABCG2 protein expression and has an impact on drug resistance.
AU  - Simon, F.*
AU  - Schwenk-Zieger, S.*
AU  - Becker, S.*
AU  - Unger, K.
AU  - Gires, O.
AU  - Baumeister, P.
C1  - 58523
C2  - 48212
CY  - Editorial Office 1st Km Kapandritiou-kalamou Rd Kapandriti, Po Box 22, Athens 19014, Greece
SP  - 1277-1284
TI  - Cigarette smoke reduces the efficacy of cisplatin in head and neck cancer cells - role of ABCG2.
JO  - Anticancer Res.
VL  - 40
IS  - 3
PB  - Int Inst Anticancer Research
PY  - 2020
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - Background/Aim: Anthracyclines have been proven able to reduce the activity of vinca alkaloids by induction of cell-cycle arrest. The present study aims at identifying the critical initiation steps of signal transduction which transduce the inhibitory effects on the cytotoxicity of vinca alkaloids. MATERIALS AND METHODS: Several new cytostatic drug classes were evaluated together with vincristine in tumor cell lines and patients' tumor cells. RNA interference was used for molecular analyses. RESULTS: Inhibition of vincristine was observed by all cytostatic drugs, which induced cell-cycle arrest. Knockdown of proteins of the DNA damage response ascribed the inhibitory effect to a common pathway involving Chk-1, p53 and p21. Upstream of Chk-1 signal transduction depended on both ATM and ATR for all drugs except methotrexate. CONCLUSION: We have identified critical signaling steps of the DNA damage response system activated by cytostatic drugs, which reduce the anti-tumor activity of vinca alkaloids. The obtained results encourage the development of novel therapeutic strategies to prevent pathway interactions based on the molecular understanding of drug action and drug-drug interactions.  
AU  - Ehrhardt, H.
AU  - Pfeiffer, S.
AU  - Schrembs, D.
AU  - Wachter, F.
AU  - Grunert, M.
AU  - Jeremias, I.
C1  - 28640
C2  - 33512
SP  - 5273-5287
TI  - Activation of DNA damage response by antitumor therapy counteracts the activity of vinca alkaloids.
JO  - Anticancer Res.
VL  - 33
IS  - 12
PB  - Int. Inst. Anticancer Research
PY  - 2013
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - BACKGROUND: Glucocorticoids are widely used for cancer patients, although they can reduce the efficacy of anticancer treatment. MATERIALS AND METHODS: We characterized non-apoptotic actions of glucocorticoids on tumor cell lines, primary tumor cells and an in vivo model, together with molecular signaling studies. RESULTS: Glucocorticoids enhanced cell proliferation in 9/17 cell lines and significantly promoted tumor cell proliferation in a pre-clinical mouse model of lung carcinoma. 65/139 primary acute childhood leukemia samples were glucocorticoid-resistant. Both dexamethasone and prednisolone increased in vitro survival in 21/65 samples from glucocorticoid-resistant primary leukemias, revealing a completely new action of glucocorticoids. Dexamethasone-induced proliferation was mediated by glucocorticoid receptor and activated the proliferation signaling pathways of protein kinase B/AKT and p38 mitogen-activated protein kinase. CONCLUSION: Our data suggest that restriction of the use of glucocorticoids during anticancer treatment might improve the outcome of patients with solid tumors.
AU  - Gündisch, S.
AU  - Boeckeler, E.
AU  - Behrends, U.
AU  - Amtmann, E.*
AU  - Ehrhardt, H.
AU  - Jeremias, I.
C1  - 11145
C2  - 30518
SP  - 4251-4261
TI  - Glucocorticoids augment survival and proliferation of tumor cells.
JO  - Anticancer Res.
VL  - 32
IS  - 10
PB  - Int. Inst. Anticancer Research
PY  - 2012
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - BACKGROUND: A new promising approach to improve the outcome of head and neck squamous cell carcinoma (HNSCC) is the application of radio-labeled antibodies directed against tumor-associated antigens. Cytokeratin 8 (CK8), an intermediate filament forming protein, is shown to be de novo expressed in dysplastic lesions as well as in HNSCC. Therefore like the epithelial cell adhesion molecule CK8 seems to be a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to investigate the biodistribution of a radio-labeled Cytokeratin 8-specific monoclonal antibody (mAb) in a SCID (severe combined immunodeficiency disease) mouse model. MATERIALS AND METHODS: The mAb against CK8 was labeled with (131)I and biodistribution was tested in established HNSCC xenografts in SCID mice. The biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. RESULTS: Initially, after systemic administration of (131)I-anti CK8 monoclonal antibody high activity was seen in all the organs. Over time the general activity decreased, whereas activity accumulated in the tumor. This activity decayed compared to the other tissues with a two- to threefold prolonged radioactive half-life. CONCLUSION: Specific antibody-antigen-binding is probably responsible for the prolonged radioactive half-life in the tumor and the resulting cumulative activity due to enrichment of the (131)I-anti CK8 mAb, so that Cytokeratin 8 seems to be a suitable anchor molecule for radioimmunotherapy in HNSCC.
AU  - Andratschke, M.*
AU  - Luebbers, C.W.*
AU  - Johannson, V.*
AU  - Schmitt, B.*
AU  - Mack, B.*
AU  - Zeidler, R.
AU  - Lang, S.*
AU  - Wollenberg, B.*
AU  - Gildehaus, F.J.*
C1  - 7113
C2  - 29599
SP  - 3315-3321
TI  - Biodistribution of 131I-labeled anti-CK8 monoclonal antibody in HNSCC in xenotransplanted SCID mice.
JO  - Anticancer Res.
VL  - 31
IS  - 10
PB  - Int. Inst. Anticancer Research
PY  - 2011
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - BACKGROUND: The mortality from squamous cell carcinoma of the head and neck (SCCHN) remains high and almost unchanged throughout the last decades. Therefore, new therapeutic strategies are urgently needed. One promising approach is the application of radio-labeled antibodies directed against tumor-associated antigens. EpCAM is a transmembrane protein, which is overexpressed on almost all SCCHN, making it a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to establish an animal model to investigate the biodistribution and the therapeutic effect of a radio-labeled EpCAM-specific monoclonal antibody (mAb). MATERIALS AND METHODS: The mAb C215 was labeled with 131I and tested for its antitumor effect against established SCCHN xenografts in SCID mice. Initially, the biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. For therapeutic approaches 5, 15 or 25 MBq 131I-labeled mAb was injected as a single bolus into tumor-bearing mice. Control animals received either sodium chloride or the unlabeled mAb. The tumor growth and body weight of the animals were measured at various times after administration of the antibody. RESULTS: Initially, high activity was seen in all organs after systemic administration of 13I-C215. Over time general activity decreased whereas an accumulation of activity was seen in the tumor. Tumor growth was delayed in the groups receiving either 15 MBq or 25 MBq 131I-C215 relative to control groups and the 5 MBq group. However, animals in the high-dose groups suffered from treatment-related toxicity, which led to body weight loss of more than 20%. CONCLUSION: Our data demonstrate that the EpCAM-specific radio-labeled mAb C215 is a promising tool to target SCCHN leading to significant tumor control. Further studies are necessary to increase efficacy and reduce toxicity of this new therapeutic approach.
AU  - Andratschke, M.*
AU  - Gildehaus, F.J.*
AU  - Johannson, V.*
AU  - Schmitt, B.*
AU  - Mack, B.*
AU  - Reisbach, G.
AU  - Lang, S.*
AU  - Lindhofer, H.*
AU  - Zeidler, R.*
AU  - Wollenberg, B.*
AU  - Luebbers, C.W.*
C1  - 27646
C2  - 32783
SP  - 431-436
TI  - Biodistribution and radioimmunotherapy of SCCHN in xenotransplantated SCID mice with a 131I-labelled anti-EpCAM monoclonal antibody.
JO  - Anticancer Res.
VL  - 27
IS  - 1A
PY  - 2007
SN  - 0250-7005
ER  - 

TY  - JOUR
AU  - Meyer, A.
AU  - Andratschke, M.*
AU  - Pauli, C.*
AU  - Reitberger, E.*
AU  - Kolbow, K.*
AU  - Wollenberg, B.*
C1  - 390
C2  - 24126
SP  - 3917-3924
TI  - Liposomal transfection of squamous carcinoma cells of the head and neck with IL-2 and B7 plasmids inducing and autologous immune response in vitro.
JO  - Anticancer Res.
VL  - 25
PY  - 2005
SN  - 0250-7005
ER  - 

TY  - JOUR
AU  - Meyer, A.
AU  - Andratschke, M.*
AU  - Pauli, C.*
AU  - Graefe, H.*
AU  - Kolbow, K.*
AU  - Wollenberg, B.*
C1  - 391
C2  - 24127
SP  - 4075-4080
TI  - Generation of an autologous cell system for immunotherapy of squamous cell carcinoma of the head and neck.
JO  - Anticancer Res.
VL  - 25
PY  - 2005
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - BACKGROUND: New adjuvant immunological therapies, that selectively redirect effector cells towards tumors, are currently under development. These strategies include trifunctional bispecific antibodies (trAb) as promising tools for the elimination of disseminated tumor cells and micrometastases. To date, these chimeric molecules have demonstrated their antitumor potential mainly in vitro. Here, trAb-activated peripheral blood mononuclear cells (PBMCs) displayed considerable antitumor activity, accompanied by the release of cytokines, which contributed to the antitumor activity but, on the other hand, may evoke serious limiting side-effects in vivo, demanding therapeutic interventions. MATERIALS AND METHODS: The antitumor activity and cytokine release by trAb-activated PBMCs were studied in co-cultures with multicellular tumor spheroids (MTS), which represent a three-dimensional in vitro model for solid tumors, especially non-vascularized micrometastases. The glucocorticoid prednisolone was tested for its influence on the release of TNF-alpha and the activity of PBMCs. RESULTS: It was shown that PBMCs, which were stimulated with a trifunctional bispecific antibody, BiUII, displayed an excellent antitumor activity, resulting in complete disintegration of the MTS. Also, it was demonstrated that prednisolone significantly reduced the release of TNF-alpha, without impairing the antitumor activity of BiUII-activated PBMCs. In contrast, unspecific killing was reduced, as demonstrated with an identical trAb (Bi48), which recognizes an antigen absent from the target cells. CONCLUSION: The in vivo application of bispecific antibodies for adjuvant tumor therapies may be limited by the manifest activation of immune effectors, accompanied by overwhelming cytokine release. Glucocorticoids, like prednisolone, may effectively reduce cytokine release without impairing the antitumor activity of trAb-activated immune cells.
AU  - Walz, A.*
AU  - Andratschke, M.*
AU  - Wollenberg, B.*
AU  - Lindhofer, H.*
AU  - Zeidler, R.
C1  - 27644
C2  - 32782
SP  - 4239-4243
TI  - Prednisolone reduces TNF-alpha release by PBMCs activated with a trifunctional bispecific antibody but not their anti-tumor activity.
JO  - Anticancer Res.
VL  - 25
IS  - 6B
PY  - 2005
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - The epithelial cell adhesion molecule EpCAM is over- or de novo expressed during carcinogenesis. EpCAM expression correlates with increased proliferation and dedifferentiation. Recently, we reported the cloning of a 1.1 kilobase fragment upstream of the epcam gene and demonstrated its specific transcriptional activity. Here, we analyzed the potential of this fragment for targeted gene expression. The fragment was used to regulate the expression of the green fluorescent protein (GFP) and HSV-1 thymidine kinase (HSV-TK), as a model therapeutic gene. Transfection of the pEpProm-control or pEpProm-GFP plasmids resulted in the expression of functional GFP and HSV-TK proteins specifically in EpCAM-positive cells. Expression levels of both proteins correlated with the amount of EpCAM. Additionally, the targeted expression of HSV1-TK transferred a marked sensitivity to ganciclovir treatment in EpCAM-positive HEK293-EBNA1 and SkBr3 carcinoma cells. The EpCAM promoter fragment is, thus, a novel tool to allow for the transcription of therapeutic genes, specifically, in EpCAM-positive carcinomas.
AU  - Gires, O.
AU  - Pöckl, S.*
AU  - Chapman, R.D.
AU  - Münz, M.
C1  - 8693
C2  - 30216
SP  - 3715-3721
TI  - Targeted gene expression using a 1.1 kilobase promoter fragment of the tumour-associated antigen EpCAM.
JO  - Anticancer Res.
VL  - 24
IS  - 6
PB  - Hellenic Anticancer Institute
PY  - 2004
SN  - 0250-7005
ER  - 

TY  - JOUR
AU  - Walz, A.*
AU  - Mack, B.*
AU  - Schmitt, B.*
AU  - Gires, O.
AU  - Wollenberg, B.*
AU  - Zeidler, R.*
C1  - 2888
C2  - 22032
SP  - 887-894
TI  - Antitumour effects of a bidpecific trivalent antibody in multicellular tumour spheroids.
JO  - Anticancer Res.
VL  - 24
PY  - 2004
SN  - 0250-7005
ER  - 

TY  - JOUR
AU  - Gires, O.
AU  - Eskofier, S.*
AU  - Lang, S.*
AU  - Zeidler, R.*
AU  - Münz, M.
C1  - 1938
C2  - 22029
SP  - 3255-3262
TI  - Cloning and characterisation of a 1.1kb fragment of the carcinoma-associated epithelial cell adhesion molecule promoter.
JO  - Anticancer Res.
VL  - 23
PY  - 2003
SN  - 0250-7005
ER  - 

TY  - JOUR
AU  - Eichholtz-Wirth, H.
AU  - Sagan, D.
C1  - 10359
C2  - 20586
SP  - 235-240
TI  - Altered signaling of TNFalpha-TNFR1 and SODD/BAG4 is responsible for radioresistance in human HT-R15 cells. 
JO  - Anticancer Res.
VL  - 22
PY  - 2002
SN  - 0250-7005
ER  - 

TY  - JOUR
AB  - The effects of the DNA polymerase inhibitors a-ara A and beta-ara C have been compared with those of beta-ara A on the endpoints of cell growth, repair of x-ray induced potentially lethal damage (PLD) and repair of x-ray induced DNA double strand breaks, a-ara A was found to have no effects on any of the endpoints studied. beta-ara C inhibited cell growth and DNA double strand breaks repair more strongly than beta-ara A but it was less effective in inhibiting repair of PLD. The inhibition of PLD repair by beta-ara C resulted in a diminution of the shoulder width of the x-ray survival curve, a result similar to that previously found for beta-ara A. The effectiveness of beta-ara C was enhanced when cells were treated with the drug in fresh medium rather than under plateau phase conditions. The lower effectiveness of beta-ara C, when compared with beta-ara A in causing expression of PLD, is interpreted in terms of a difference in the ability of the two drugs to cause fixation or misrepair of the DNA double strand breaks during or after treatment with the drugs.
AU  - Iliakis, G.E.
AU  - Bryant, P.E.
C1  - 41406
C2  - 37731
SP  - 143-149
TI  - Effects of the nucleoside analogues α-ara A, β-ara A and β-ara C on cell growth and repair of both potentially lethal damage and DNA double strand breaks in mammalian cells in culture.
JO  - Anticancer Res.
VL  - 3
IS  - 2
PY  - 1983
SN  - 0250-7005
ER  -