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
Type of Medium
Language
Year
  • 1
    Language: English
    In: Oncogene, August 2018, Vol.37(33), pp.4546-4561
    Description: Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.
    Keywords: Drug Resistance, Neoplasm -- Physiology ; Reactive Oxygen Species -- Metabolism ; Triple Negative Breast Neoplasms -- Metabolism
    ISSN: 09509232
    E-ISSN: 1476-5594
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Cancer Research, 07/01/2018, Vol.78(13 Supplement), pp.1348-1348
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Cancer and Metastasis Reviews, 2018, Vol.37(4), pp.749-766
    Description: Resistance to therapy is one of the prime causes for treatment failure in cancer and recurrent disease. In recent years, autophagy has emerged as an important cell survival mechanism in response to different stress conditions that are associated with cancer treatment and aging. Autophagy is an evolutionary conserved catabolic process through which damaged cellular contents are degraded after uptake into autophagosomes that subsequently fuse with lysosomes for cargo degradation, thereby alleviating stress. In addition, autophagy serves to maintain cellular homeostasis by enriching nutrient pools. Although autophagy can act as a double-edged sword at the interface of cell survival and cell death, increasing evidence suggest that in the context of cancer therapy-induced stress responses, it predominantly functions as a cell survival mechanism. Here, we provide an up-to-date overview on our current knowledge of the role of pro-survival autophagy in cancer therapy at the preclinical and clinical stages and delineate the molecular mechanisms of autophagy regulation in response to therapy-related stress conditions. A better understanding of the interplay of cancer therapy and autophagy may allow to unveil new targets and avenues for an improved treatment of therapy-resistant tumors in the foreseeable future.
    Keywords: Cancer ; Therapy resistance ; Stress condition ; Pro-survival autophagy
    ISSN: 0167-7659
    E-ISSN: 1573-7233
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Cell Proliferation, February 2018, Vol.51(1), pp.n/a-n/a
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/cpr.12411/abstract Byline: Prajna Paramita Naik, Subhadip Mukhopadhyay, Prashanta Kumar Panda, Niharika Sinha, Chandan Kanta Das, Rajakishore Mishra, Shankargouda Patil,Sujit Kumar Bhutia Keywords: ABCB1; ADAM17; autophagy; CD44; chemoresistance; stemness Abstract Objective We inspected the relevance of CD44, ABCB1 and ADAM17 in OSCC stemness and deciphered the role of autophagy/mitophagy in regulating stemness and chemoresistance. Material and methods A retrospective analysis of CD44, ABCB1 and ADAM17 with respect to the various clinico-pathological factors and their correlation was analysed in sixty OSCC samples. Furthermore, the stemness and chemoresistance were studied in resistant oral cancer cells using sphere formation assay, flow cytometry and florescence microscopy. The role of autophagy/mitophagy was investigated by transient transfection of siATG14, GFP-LC3, tF-LC3, mKeima-Red-Mito7 and Western blot analysis of autophagic and mitochondrial proteins. Results In OSCC, high CD44, ABCB1 and ADAM17 expressions were correlated with higher tumour grades and poor differentiation and show significant correlation in their co-expression. In vitro and OSCC tissue double labelling confirmed that CD44.sub.+ cells co-expresses ABCB1 and ADAM17. Further, cisplatin (CDDP)-resistant FaDu cells displayed stem-like features and higher CD44, ABCB1 and ADAM17 expression. Higher autophagic flux and mitophagy were observed in resistant FaDu cells as compared to parental cells, and inhibition of autophagy led to the decrease in stemness, restoration of mitochondrial proteins and reduced expression of CD44, ABCB1 and ADAM17. Conclusion The CD44.sub.+/ABCB1.sub.+/ADAM17.sub.+ expression in OSCC is associated with stemness and chemoresistance. Further, this study highlights the involvement of mitophagy in chemoresistance and autophagic regulation of stemness in OSCC. CAPTION(S):
    Keywords: Abcb 1 ; Adam 17 ; Autophagy ; Cd 44 ; Chemoresistance ; Stemness
    ISSN: 0960-7722
    E-ISSN: 1365-2184
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: RSC Advances, 2016, Vol.6(75), pp.71612-71623
    Description: Lipopeptides are versatile bio-active weapons having antifungal, antibacterial, antimycoplasma and anticancer properties. In this study, the therapeutic potential and safety assessment of a lipopeptide molecule Iturin A were evaluated. Iturin A was found to inhibit in vivo tumor growth in a sarcoma 180 mouse xenograft model. The antitumor efficacy of Iturin A was correlated with increased DNA fragmentation and modulation of CD-31, Ki-67, P-Akt, P-MAPK, apoptotic and anti-apoptotic proteins. Further, safety assessment was carried out in Sprague Dawley rats by 28 days repeated dose (28 days) toxicity and a bio-distribution study. In the toxicity study, Iturin A (10, 20 and 50 mg per kg per day) was administered to the animals for 28 days. Another group was kept for another 14 days without drug exposure after 28 days of treatment to access the reversibility of the toxicity. At the end of the treatment, body weight, food and water intake, organ weight, motility, hematology, serum biochemistry and histopathology of the major organs were evaluated. The bio-distribution of Iturin A was also performed in plasma as well as in different major organs by a well-developed and validated administration of Iturin A radiolabeled with 99m Tc. The in vitro cytotoxic effect of Iturin A was also evaluated in BRL-3A rat liver cells. In the treated groups, various toxicities were found in the liver and spleen. However, these adverse effects were transient and reversible after discontinuation of Iturin A treatment. In conclusion, this pre-clinical study offered a preliminary investigation regarding the efficacy and safety assessment of Iturin A.
    Keywords: Biocompatibility ; In Vitro Testing ; Assessments ; Safety ; Liver ; Iturin A ; Toxicity ; Effectiveness ; Chemical and Electrochemical Properties (MD) ; Chemical and Electrochemical Properties (Ep) ; Chemical and Electrochemical Properties (Ed) ; Chemical and Electrochemical Properties (EC);
    ISSN: 2046-2069
    E-ISSN: 2046-2069
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Neoplasia, March 2018, Vol.20(3), pp.263-279
    Description: Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549 DOX ) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468 5-FU ) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549 DOX and MDA-MB-468 5-FU cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer.
    Keywords: Medicine
    ISSN: 1476-5586
    E-ISSN: 1476-5586
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Das, Chandan Kanta and Linder, Benedikt and Bonn, Florian and Rothweiler, Florian and Dikic, Ivan and Michaelis, Martin and Cinatl, Jindrich and Mandal, Mahitosh and Kögel, Donat (2018) BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells. Neoplasia, 20 (3). pp. 263-279.
    Description: Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549DOX) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-4685-FU) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549DOX and MDA-MB-4685-FU cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer.
    Keywords: RM Therapeutics. Pharmacology
    ISSN: 1476-5586
    Source: University of Kent
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: Food and Chemical Toxicology, February 2014, Vol.64, pp.369-377
    Description: In this study we unravel the mechanism underlying the antitumorigenic effects of Peanut agglutinin (PNA) isolated from in Dalton’s lymphoma (DL) bearing mice and elucidated the mechanism in HeLa cells. PNA administration at 1 and 2 mg/kg body weight reduced DL proliferation with increase in autophagic and apoptotic characteristics. data showed that PNA at 0.1–100 μg/ml dose exhibit selective antiproliferative activity on various cancer cell lines without displaying cytotoxic effect on normal cells. However, heat denatured PNA failed to show any antiproliferative activity. Moreover, PNA was found to induce autophagic and apoptotic cell death in HeLa cells. Exponential increase in reactive oxygen species (ROS) was proved to be the master signal for promoting PNA induced cell death in HeLa cells. Interestingly, when HeLa cells were pre-exposed with N-acetylcysteine (NAC) and followed to PNA treatment, there was sharp decline in autophagy, apoptosis and a concomitant abrogation of antiproliferative potential. PNA at lower doses was also seen to inflict senescence. Hence, this common culinary item derived molecule whose discovery dates back to late 1970s was for the first time evaluated mechanistically and as a novel naturally occurring therapeutic agent against cancer.
    Keywords: Peanut Agglutinin ; Apoptosis ; Autophagy ; Ros ; Senescence ; Dalton’s Lymphoma ; Chemistry ; Public Health ; Economics
    ISSN: 0278-6915
    E-ISSN: 1873-6351
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Cancer Letters, 01 March 2017, Vol.388, pp.292-302
    Description: Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy.
    Keywords: Liposome ; Somatostatin Analogue (Sst) ; Diacerein and Breast Cancer ; Medicine
    ISSN: 0304-3835
    E-ISSN: 1872-7980
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Seminars in cancer biology, 17 August 2019
    Description: Autophagy is an evolutionary conserved catabolic process that regulates the cellular homeostasis by targeting damaged cellular contents and organelles for lysosomal degradation and sustains genomic integrity, cellular metabolism, and cell survival during diverse stress and adverse conditions. Recently, the role of autophagy is extremely debated in the regulation of cancer initiation and progression. Although autophagy has a dichotomous role in the regulation of cancer, growing numbers of studies largely indicate the pro-survival role of autophagy in cancer progression and metastasis. In this review, we discuss the detailed mechanisms of autophagy, the role of pro-survival autophagy that positively drives several classical as well as emerging hallmarks of cancer for tumorigenic progression, and also we address various autophagy inhibitors that could be harnessed against pro-survival autophagy for effective cancer therapeutics. Finally, we highlight some outstanding problems that need to be deciphered extensively in the future to unravel the role of autophagy in tumor progression.
    Keywords: Cancer ; Hallmarks ; Inhibitors ; Pro-Survival Autophagy
    ISSN: 1044579X
    E-ISSN: 1096-3650
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
    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