Search results for "BC"
showing 10 items of 1938 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…
Role of AxyZ Transcriptional Regulator in Overproduction of AxyXY-OprZ Multidrug Efflux System in Achromobacter Species Mutants Selected by Tobramycin
2017
ABSTRACT AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ . An in-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system, including aminoglycosides, cefepime, fluoroquinolones, tetracyclines, and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ . Moreover, we identified an amino acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract…
High-throughput sequencing for 1-methyladenosine (m1A) mapping in RNA
2016
Abstract Detection and mapping of modified nucleotides in RNAs is a difficult and laborious task. Several physico-chemical approaches based on differential properties of modified nucleotides can be used, however, most of these methods do not allow high-throughput analysis. Here we describe in details a method for mapping of rather common 1-methyladenosine (m1A) residues using high-throughput next generation sequencing (NGS). Since m1A residues block primer extension during reverse transcription (RT), the accumulation of abortive products as well as the nucleotide misincorporation can be detected in the sequencing data. The described library preparation protocol allows to capture both types …
Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone
2016
Abstract Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thu…
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced…
2019
Abstract Purpose: IDO1 induces immune suppression in T cells through l-tryptophan (Trp) depletion and kynurenine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T cells and hyperactivating regulatory T cells (Treg). Navoximod is an investigational small-molecule inhibitor of IDO1. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer. Patients and Methods: The study consisted of a 3+3 dose-escalation stage (n = 66) and a tumor-specific expansion stage (n = 92). Navoximod was given orally every 12 hours continuously for 21 consecu…
Effect of ABC transporter expression and mutational status on survival rates of cancer patients
2020
ATP-binding cassette (ABC) transporters mediate multidrug resistance in cancer. In contrast to DNA single nucleotide polymorphisms in normal tissues, the role of mutations in tumors is unknown. Furthermore, the significance of their expression for prediction of chemoresistance and survival prognosis is still under debate. We investigated 18 tumors by RNA-sequencing. The mutation rate varied from 27,507 to 300885. In ABCB1, three hotspots with novel mutations were in transmembrane domains 3, 8, and 9. We also mined the cBioPortal database with 11,814 patients from 23 different tumor entities. We performed Kaplan-Meier survival analyses to investigate the effect of ABC transporter expression …
Malignant granular cell tumor of soft tissues: a study of two new cases.
2001
We describe 2 cases of malignant granular cell tumor. A marked discrepancy exists concerning the criteria of malignancy of this rare entity, which was diagnosed in male patients aged 41 and 52 years, respectively. They presented with tumors measuring more then 3.5 cm; one arose in the dermis and subcutaneous tissue in the region of the scapula, whereas the other was situated in deeper soft tissue in the pelvis. One case, with previous diagnosis of benign granular cell tumor, presented local recurrence 2 years after the initial diagnosis. The other case presented a fascicular pattern of growth invading adjacent muscular tissue. Both neoplasms were composed of polygonal and spindle cells, sho…
Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.
2016
24 páginas, 7 figuras. Borras C, et al. Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging. Aging (Albany NY). 2016 Oct 28;8(12):3185-3208. doi: 10.18632/aging.101078.
Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells
2016
Summary Dietary leucine has been suspected to play an important role in insulin release, a hormone that controls satiety and metabolism. The mechanism by which insulin-producing cells (IPCs) sense leucine and regulate insulin secretion is still poorly understood. In Drosophila, insulin-like peptides (DILP2 and DILP5) are produced by brain IPCs and are released in the hemolymph after leucine ingestion. Using Ca2+-imaging and ex vivo cultured larval brains, we demonstrate that IPCs can directly sense extracellular leucine levels via minidiscs (MND), a leucine transporter. MND knockdown in IPCs abolished leucine-dependent changes, including loss of DILP2 and DILP5 in IPC bodies, consistent wit…