Search results for "response"

The morphogenetically active polymer, inorganic polyphosphate complexed with GdCl 3 , as an inducer of hydroxyapatite formation in vitro

2015

Inorganic polyphosphate (polyP) is a physiological polymer composed of tens to hundreds of phosphate units linked together via phosphoanhydride bonds. Here we compared the biological activity of polyP (chain length of 40 phosphate units), complexed with Gd(3+) (polyP·Gd), with the one caused by polyP (as calcium salt) and by GdCl3 alone, regarding their potencies to induce hydroxyapatite (HA) formation in SaOS-2 cells in vitro. The three compounds, GdCl3, polyP and polyP·Gd were found to be non-toxic at concentrations up to at least 30μM. Selecting a low, 5μM, concentration it was found that polyP·Gd significantly induced HA formation, as determined by Alizarin Red S staining and by quantit…

Dibutyltin(IV) and Tributyltin(IV) Derivatives of meso-Tetra(4 sulfonatophenyl)porphine Inhibit the Growth and the Migration of Human Melanoma Cells.

2019

Melanoma is the most aggressive and deadly form of skin cancer, which is largely due to its propensity to metastasize. Therefore, with the aim to inhibit the growth and the metastatic dissemination of melanoma cells and to provide a novel treatment option, we studied the effects of the melanoma treatment with two organotin(IV) complexes of the meso-tetra(4-sulfonato-phenyl)porphine, namely (Bu2Sn)2TPPS and (Bu3Sn)4TPPS. In particular, we showed that nanomolar concentrations of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS are sufficient to inhibit melanoma cell growth, to increase the expression of the full-length poly (ADP-ribose) polymerase (PARP-1), to induce the cell cycle arrest respectively at G2/M a…

Viral fitness correlates with the magnitude and direction of the perturbation induced in the host’s transcriptome: the tobacco etch Potyvirus—tobacco…

2018

Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyv…

Updated Results from the German Mpnsg-0212 Combination Trial: Ruxolitinib Plus Pomalidomide in Myelofibrosis with Anemia

2019

Background: Anemia remains one cardinal symptom associated with reduced quality of life (QoL) in patients (pts) with myelofibrosis (MF) which is normally not being addressed by ruxolitinib (RUX). In our previous MPNSG-0109 trial, single-agent pomalidomide (POM) improved cytopenia in 14% (POM 0.5 mg QD) and 29% (POM 2.0 mg QD) of MF pts, respectively. In the MPNSG-0212 study, we sought to investigate the potential synergism of RUX plus POM to improve anemia and QoL in MF pts. Study Design: MPNSG-0212 is an ongoing multicenter, open-label, single-arm phase-Ib/II trial with a target population of 90 pts following a two-stage design (NCT01644110). Pts 1-40 in cohort 1 (co1) were treated with RU…

Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat cells

2018

Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5 mu M; 24 h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations. Gene ontology (GO) analysis showed several biological processes related to electron transport chain, oxidative phosphorylation, and cel…

2021

While the importance of the iron-load of lipocalin-2 (Lcn-2) in promoting tumor progression is widely appreciated, underlying molecular mechanisms largely remain elusive. Considering its role as an iron-transporter, we aimed at clarifying iron-loaded, holo-Lcn-2 (hLcn-2)-dependent signaling pathways in affecting renal cancer cell viability. Applying RNA sequencing analysis in renal CAKI1 tumor cells to explore highly upregulated molecular signatures in response to hLcn-2, we identified a cluster of genes (SLC7A11, GCLM, GLS), which are implicated in regulating ferroptosis. Indeed, hLcn-2-stimulated cells are protected from erastin-induced ferroptosis. We also noticed a rapid increase in rea…

Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment.

2021

Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infe…

The anti-cancer drug doxorubicin induces substantial epigenetic changes in cultured cardiomyocytes.

2019

Abstract The anthracycline doxorubicin (DOX) is widely used in cancer therapy with the limitation of cardiotoxicity leading to the development of congestive heart failure. DOX-induced oxidative stress and changes of the phosphoproteome as well as epigenome were described but the exact mechanisms of the adverse long-term effects are still elusive. Here, we tested the impact of DOX treatment on cell death, oxidative stress parameters and expression profiles of proteins involved in epigenetic pathways in a cardiomyocyte cell culture model. Markers of oxidative stress, apoptosis and expression of proteins involved in epigenetic processes were assessed by immunoblotting in cultured rat myoblasts…

Anticancer metal drugs and immunogenic cell death

2016

Conventional chemotherapeutics, but also innovative precision anticancer compounds, are commonly perceived to target primarily the cancer cell compartment. However, recently it was discovered that some of these compounds can also exert immunomodulatory activities which might be exploited to synergistically enhance their anticancer effects. One specific phenomenon of the interplay between chemotherapy and the anticancer immune response is the so-called “immunogenic cell death” (ICD). ICD was discovered based on a vaccination effect exerted by cancer cells dying from pretreatment with certain chemotherapeutics, termed ICD inducers, in syngeneic transplantation mouse models. Interestingly, onl…

SERCA and P-glycoprotein inhibition and ATP depletion are necessary for celastrol-induced autophagic cell death and collateral sensitivity in multidr…

2019

Multidrug resistance (MDR) represents an obstacle in anti-cancer therapy. MDR is caused by multiple mechanisms, involving ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), which reduces intracellular drug levels to sub-therapeutic concentrations. Therefore, sensitizing agents retaining effectiveness against apoptosis- or drug-resistant cancers are desired for the treatment of MDR cancers. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump is an emerging target to overcome MDR, because of its continuous expression and because the calcium transport function is crucial to the survival of tumor cells. Previous studies showed that SERCA inhibitors exhibit anti-c…