Search results for "Hera"
showing 10 items of 14928 documents
Repurposing of Bromocriptine for Cancer Therapy
2018
Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson’s disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 brea…
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
2018
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study wer…
Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infecti…
2018
ESGAP, ESGBIS, ESGIE and the CRGNB treatment survey study group.
Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology
2018
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug’s activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1.88). Drug-resistant U87.MG ΔEGFR glioblastoma cells harboring mutated epidermal growth factor receptor were even more sensitive (collateral sensitive) than wild-type U87.MG cells (…
Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition
2016
AbstractA fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved …
Assessment of tumor-infiltrating TCRV γ 9V δ 2 γδ lymphocyte abundance by deconvolution of human cancers microarrays
2017
Most human blood γδ cells are cytolytic TCRVγ9Vδ2+lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes. Here, by implementing machine learning from microarray data, we first improved the computational identification of blood-derived TCRVγ9Vδ2+γδ lymphocytes and then appl…
Human ectonucleotidase-expressing CD25 high Th17 cells accumulate in breast cancer tumors and exert immunosuppressive functions
2015
IF 7.644; International audience; Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Ror gamma t and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-beta and IL-6. Finally, immunohistochemical …
IL10 promoter haplotypes may contribute to altered cytokine expression and systemic inflammation in celiac disease
2018
Celiac disease (CD) is an autoimmune/inflammatory condition triggered by dietary gluten intake in genetically predisposed individuals. Though associations with MHC class II HLA-DQ2 or -DQ8 are the primary and necessary genetic predisposition for CD, >97% of genetically predisposed individuals never develop CD. Cytokines were measured in the serum of CD patients and controls. Possible associations with IL10 promoter variants were investigated. Cytokine expression from PBMCs was monitored in response to gluten exposure, or CD3/TCR complex stimulation in the absence or presence of recombinant IL-10. Serum cytokines varied between patients with CD at the time of diagnosis, after dietary elimina…
Mutanome directed cancer immunotherapy
2015
Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the reperto…
γδ cells and tumor microenvironment: A helpful or a dangerous liason?
2017
Abstract γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy. One of the most important limits is the possible polarization of tumor-infiltrating γδ T cells toward different γδ T…