Recombinant bispecific antibodies such as tandem scFv molecules (taFv), diabodies (Db), or single chain (scDb) have shown to be able retarget T lymphocytes tumor cells, leading their destruction. However, therapeutic efficacy is hampered by a short serum half-life of these small having molecule masses 50-60 kDa. Thus, improvement the pharmacokinetic properties antibody formats required enhance in vivo. In this study, we generated several recombinant antibody-albumin fusion proteins and...

There is evidence that the extent of G2/M arrest following irradiation correlated with tumour cell survival and hence therapeutic success. We studied regulation cellular response to radiation treatment by miR-21-mediated modulation cycle progression in breast cancer cells analysed miR-21 expression tissue samples long-term follow up. The levels were quantified (qRT-PCR) a panel 86 cases invasive carcinomas relation metastasis free survival. radiosensitivity human after was determined...

MiR-221/-222 are frequently overexpressed in breast cancer and associated with increased malignancy. The specific modification of microRNAs (miRNAs) expression could be a promising strategy therapy, leading to the suppression tumourigenic processes tumour cells. expressions were analysed 86 tissues by quantitative RT–PCR tested for correlation immunohistochemistry data clinical follow-up. In vitro assays conducted using human cell lines lentiviral overexpression miR-221/-222. tissues,...

Radiation resistance presents a challenge to the effective treatment of cancer. If therapeutic compounds were capable resensitizing resistant tumours then concurrent chemo-radiation could be used overcome radiation resistance. We have developed phenotypic assay investigate response breast cancer cells grown in 3D-microtissue spheroids combinations and established chemotherapeutic drugs. The effects quantified by real time high content imaging GFP detection area over 14 days. Ten drugs tested...

Mesenchymal stem cells (MSCs) are attracting increasing interest for cell-based therapies, making use of both their immuno-modulating and regenerative potential. For such therapeutic applications, a massive in vitro expansion donor is usually necessary to furnish sufficient material transplantation. It not established what extent the long-term genomic stability potency MSCs can be compromised as result this rapid ex vivo expansion. In study, we investigated DNA damage response chromosomal...

Abstract Background Although lentiviral transduction methods are widely used, their broader application is dependent upon the optimization of efficiency for a broad range cell types. In present study, we focus on evaluation two chemical classes with respect to ability increase without cytotoxicity. Methods We compared activity adjuvants that already used lentivirus delivery novel selected basis and physical characteristics. Results The poloxamer synperonic F108 demonstrated superior...

A 3D microtissues using T47D and JIMT-1 cells were generated to analyze tissue-like response of breast cancer after combined human epidermal growth factor receptor 2 (HER2)-targeted treatment radiation. Following lentiviral knockdown HER2, we compared rate alterations 2D monolayers, microtissues, mouse xenografts. Additionally, model therapeutic strategies, treated HER2-depleted trastuzumab (anti-HER2 antibody) in combination with irradiation. Comparison HER2 corresponding controls revealed...

During polychemotherapy, cytotoxic drugs are given in combinations to enhance their anti-tumor effectiveness. For most drug combinations, underlying signaling mechanisms responsible for positive drug–drug interactions remain elusive. Here, we prove a decisive role the Bcl-2 family member NOXA mediate cell death by certain even if were combined which acted independently from NOXA, when alone. In proof-of-principle studies, betulinic acid, doxorubicin and vincristine induced p53-...

// Ines Leinhäuser 1, 2 , Andrea Richter 1 Misu Lee Höfig Nataša Anastasov Falko Fend 3 Tonino Ercolino 4 Massimo Mannelli 5 Anne-Paule Gimenez-Roqueplo 6, 7, 8 Mercedes Robledo 9 Ronald de Krijger 10 Felix Beuschlein 11 Michael J. Atkinson Natalia S. Pellegata Institute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany Radiation Biology, Pathology and Neuropathology Comprehensive Cancer Center Tübingen University Tübingen, Azienda Ospedaliero-Universitaria di Careggi, Endocrine...

The human epidermal growth factor receptor 2 (HER2) and the protein tyrosine kinase 6 (PTK6) are often co‐ over‐expressed in invasive breast cancers. At early diagnosis, only distinct groups, such as HER2‐or hormone receptor‐positive benefit from a targeted therapy. However, part of these tumours develops resistance within year administration drug but majority patients depends on general therapies with severe side effects. A PTK6‐directed approach does not yet exist. In our present study, we...

Mesenchymal stem cells (MSCs) are a source of adult multipotent important in tissue regeneration. Murine MSCs known to proliferate poorly vitro under normoxia. The aim this study is analyze the interaction nonphysiological high oxygen and low‐dose γ ‐irradiation onto growth, senescence, DNA damage. Tri‐potent bone marrow‐derived from p53 wildtype p53−/− mice were cultured either 21% or 2% O 2 . Long‐term observations revealed decreasing ability mMSCs form colonies extended culture This was...

Abstract Background Signaling studies in cell lines are hampered by non-physiological alterations obtained vitro. Physiologic primary tumor cells from patients with leukemia require passaging through immune-compromised mice for amplification. The aim was to enable molecular work patients' ALL establishing siRNA transfection into amplified mice. Results We established delivering these without affecting viability. Knockdown of single or multiple genes reduced constitutive induced protein...

Abstract Background We present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction from transcriptomic microarray data. was previously identified as potential marker for radiation induced papillary thyroid carcinoma (PTC) young patients in aftermath Chernobyl reactor accident. Considering rising cancer incidence rates western societies, potentially related to medical exposure, characterization is relevance and contributes knowledge about...

Abstract Introduction Rats carrying a germline loss-of-function mutation in p27 (MENX syndrome) develop bilateral pheochromcoytoma (PCC) with complete penetrance. Gene expression profiling of rat PCCs identified genes highly expressed tumors versus normal adrenal medulla. Several them were found up-regulated also human (both sporadic and familial), including the BMP7 gene encoding member bone morphogenic protein family. has been shown to be involved other cancers, but its role PCC...

Abstract A stem cell like subpopulation of human T47D and MDA-MB-361 breast cancer cells (CD44+CD24-) was enriched by irradiation (2 Gy) isolated using magnetic activated sorting. As an additional model, primary murine mesenchymal (MSCs) were from the bone marrow C3HxBL mice. We confirmed stemness phenotype repopulating heterogeneous lines CD44+CD24- or inducing differentiation MSCs to osteocyte, adipocyte chondrocyte lineage. For gene delivery in research, lentiviral transduction protocols...

Abstract Among breast cancer patients, radiation therapy resistance is a common problem in treatment. Overcoming the mechanisms responsible for this phenotype an ongoing challenge. Options include repurposing established chemotherapeutics and discovery of new radiosensitizing compounds. Three-dimensional (3D) microtissue models offer physiological environment efficient preclinical drug testing. We have adopted 3D technology (Insphero, AG) to generate highly reproducible mammary microtissues...

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)

Abstract Although lentiviral transduction methods are widely used in cancer research their application is frequently hindered by the low efficiency seen for a number of different cell types, particular primary cells. We have previously reported that mixture poloxamer synperonic F108 and polybrene combines reduced toxicity increased gene delivery into range cultures (1). now report further improvement through novel combination poloxamer-based adjuvant with modified envelope. The envelope was...

Abstract The two key issues in chemo- and radiation therapy is the development of tumor resistance as well toxic effects on normal tissue. In this sense new strategies are required to increase efficacy improve therapeutic impact reduce toxicological side effects. performance 3D cell culture systems over classical 2D has been shown provide a closer representation tissue-level biology. This led rapid adoption for both drug discovery toxicology. InSphero developed highly reproducible hanging...