Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Language
Year
  • 1
    Language: English
    In: International Journal of Pharmaceutics, 30 January 2013, Vol.441(1-2), pp.499-506
    Description: In this work, we evaluated combinations of doxorubicin with INNO-206, a (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) that is currently undergoing two phase II clinical trials, in a primarily chemoresistant tumor indication, pancreatic cancer. Thus, we compared the antitumor efficacy and tolerability of the following weekly intravenous treatments in the MIA PaCa-2 xenograft model: 3 × 6 mg doxorubicin (MTD), 3 × 24 mg/kg DOXO-EMCH (doxorubicin equivalents, MTD), 3 × 3 mg/kg doxorubicin followed 6 h later by 3 × 12 mg/kg DOXO-EMCH, and 3 × 12 mg/kg DOXO-EMCH followed 6 h later by 3 × 3 mg/kg doxorubicin. Whereas therapy with doxorubicin only produced a moderate tumor inhibition, all other therapy arms induced complete and partial remissions up to the end of the experiment on day 43. Although the total amount of doxorubicin equivalents is 72 mg/kg when DOXO-EMCH is administered alone, but only 45 mg/kg doxorubicin equivalents are administered in the combination regimens, the antitumor efficacy in all treated groups was essentially identical, a surprising finding of this study. However, there were significant differences in the tolerability as assessed by the body weight changes: whereas therapy at the MTD of DOXO-EMCH (3 × 24 mg/kg) produced a body weight loss of −16% including one death, therapy with 3 × 12 mg/kg DOXO-EMCH followed 6 h later by 3 × 3 mg/kg doxorubicin produced −7% body weight loss, and 3 × 3 mg/kg doxorubicin followed 6 h later by 3 × 12 mg/kg DOXO-EMCH produced a body weight gain of +2% as a clear indication of minimal systemic toxicity. In addition, cell culture experiments revealed additive to synergistic effects when MIA PaCa-2 cells were exposed to doxorubicin followed 6 h later to exposure of the albumin-bound form of DOXO-EMCH spanning a ratio of 1:5 to 5:1 (analyzed for synergistic, additive or antagonistic effects using the software program CalcuSyn ). This animal study demonstrates that the time-dependent schedule of an albumin-binding prodrug and a free drug has a critical influence on the overall tolerability. A combination of doxorubicin and DOXO-EMCH is currently being investigated in a phase Ib study.
    Keywords: Doxorubicin ; (6-Maleimidocaproyl)Hydrazone of Doxorubicin ; Doxo-Emch ; Inno-206 ; Prodrugs ; Human Serum Albumin ; Combination Therapy ; Pancreatic Cancer ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Cancer Research, 04/15/2011, Vol.71(8 Supplement), pp.2569-2569
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: PLoS ONE, 2014, Vol.9(5)
    Description: Background Large-scale genomic analyses of patient cohorts have revealed extensive heterogeneity between individual tumors, contributing to treatment failure and drug resistance. In malignant melanoma, heterogeneity is thought to arise as a consequence of the differentiation of melanoma-initiating cells that are defined by cell-surface markers like CD271 or CD133. Results Here we confirmed that the nerve growth factor receptor (CD271) is a crucial determinant of tumorigenicity, stem-like properties, heterogeneity and plasticity in melanoma cells. Stable shRNA mediated knock-down of CD271 in patient-derived melanoma cells abrogated their tumor-initiating and colony-forming capacity. A genome-wide expression profiling and gene-set enrichment analysis revealed novel connections of CD271 with melanoma-associated genes like CD133 and points to a neural crest stem cell (NCSC) signature lost upon CD271 knock-down. In a meta-analysis we have determined a shared set of 271 differentially regulated genes, linking CD271 to SOX10, a marker that specifies the neural crest. To dissect the connection of CD271 and CD133 we have analyzed 10 patient-derived melanoma-cell strains for cell-surface expression of both markers compared to established cell lines MeWo and A375. We found CD271 + cells in the majority of cell strains analyzed as well as in a set of 16 different patient-derived melanoma metastases. Strikingly, only 2/12 cell strains harbored a CD133 + sub-set that in addition comprised a fraction of cells of a CD271 + /CD133 + phenotype. Those cells were found in the label-retaining fraction and in vitro deduced from CD271 + but not CD271 knock-down cells. Conclusions Our present study provides a deeper insight into the regulation of melanoma cell properties and points CD271 out as a regulator of several melanoma-associated genes. Further, our data strongly suggest that CD271 is a crucial determinant of stem-like properties of melanoma cells like colony-formation and tumorigenicity.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Pharmaceutical Research, 2012, Vol.29(7), pp.1949-1959
    Description: Byline: Andrea Orthmann (1), Reiner Zeisig (2), Regine Suss (3), Dorothea Lorenz (4), Margit Lemm (1), Iduna Fichtner (1) Keywords: brain metastases; LRP; targeting; transcytosis; uptake Abstract: Purpose To test targeted liposomes in an effort to improve drug transport across cellular barriers into the brain. Methods Therefore we prepared Mitoxantrone (MTO) entrapping, rigid and fluid liposomes, equipped with a 19-mer angiopeptide as ligand for LDL lipoprotein receptor related protein (LRP) targeting. Results Fluid, ligand bearing liposomes showed in vitro the highest cellular uptake and transcytosis and were significantly better than the corresponding ligand-free liposomes and rigid, ligand-bearing vesicles. Treatment of mice, transplanted with human breast cancer cells subcutaneously and into the brain, with fluid membrane liposomes resulted in a significant reduction in the tumor volume by more than 80% and in a clear reduction in drug toxicity. The improvement was mainly depended on liposome fluidity while the targeting contributed only to a minor degree. Pharmacokinetic parameters were also improved for liposomal MTO formulations in comparison to the free drug. So the area under the curve was increased and t.sub.1/2 was extended for liposomes. Conclusion Our data show that it is possible to significantly improve the therapy of brain metastases if MTO-encapsulating, fluid membrane liposomes are used instead of free MTO. This effect could be further enhanced by fluid, ligand bearing liposomes. Author Affiliation: (1) Experimental Pharmacology, Max Delbruck Center for Molecular Medicine, Robert-Rossle-Str. 10, 13125, Berlin-Buch, Germany (2) Experimental Pharmacology & Oncology Berlin-Buch GmbH, Robert-Rossle-Str. 10, 13125, Berlin-Buch, Germany (3) Department of Pharmaceutical Technology and Biopharmacy, Albert-Ludwigs University, Stefan-Meier-Str. 19, 79104, Freiburg, Germany (4) Cellular Imaging Leibniz-Institut fur Molekulare Pharmakologie (FMP), Robert-Rossle-Str. 10, 13125, Berlin, Germany Article History: Registration Date: 24/02/2012 Received Date: 05/01/2012 Accepted Date: 24/02/2012 Online Date: 08/03/2012 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s11095-012-0723-7) contains supplementary material, which is available to authorized users.
    Keywords: brain metastases ; LRP ; targeting ; transcytosis ; uptake
    ISSN: 0724-8741
    E-ISSN: 1573-904X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: PLoS ONE, 2011, Vol.6(5), p.e20550
    Description: Breast cancer is the most common cancer and the second leading cause of cancer death in industrialized countries. Systemic treatment of breast cancer is effective at the beginning of therapy. However, after a variable period of time, progression occurs due to therapy resistance. Artesunate, clinically used as anti-malarial agent, has recently revealed remarkable anti-tumor activity offering a role as novel candidate for cancer chemotherapy. We analyzed the anti-tumor effects of artesunate in metastasizing breast carcinoma in vitro and in vivo . Unlike as expected, artesunate induced resistance in highly metastatic human breast cancer cells MDA-MB-231. Likewise acquired resistance led to abolishment of apoptosis and cytotoxicity in pre-treated MDA-MB-231 cells. In contrast, artesunate was more cytotoxic towards the less tumorigenic MDA-MB-468 cells without showing resistance. Unraveling the underlying molecular mechanisms, we found that resistance was induced due to activation of the tumor progression related transcription factors NFκB and AP-1. Thereby transcription, expression and activity of the matrix-degrading enzyme MMP-1, whose function is correlated with increased invasion and metastasis, was up-regulated upon acquisition of resistance. Additionally, activation of the apoptosis-related factor NFκB lead to increased expression of ant-apoptotic bcl2 and reduced expression of pro-apoptotic bax . Application of artesunate in vivo in a model of xenografted breast cancer showed, that tumors growth was not efficiently abolished as compared to the control drug doxorubicin. Taken together our in vitro and in vivo results correlate well showing for the first time that artesunate induces resistance in highly metastatic breast tumors.
    Keywords: Research Article ; Biology ; Chemistry ; Medicine ; Chemistry ; Oncology ; Pharmacology
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Cancer Research, 08/01/2015, Vol.75(15 Supplement), pp.3225-3225
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Cancer Research, 07/15/2016, Vol.76(14 Supplement), pp.5200-5200
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Cancer Research, 10/01/2014, Vol.74(19 Supplement), pp.4953-4953
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.3800-3800
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Cancer Research, 07/01/2017, Vol.77(13 Supplement), pp.1697-1697
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages