11 research outputs found
Surface properties of polyetheretherketone after different laboratory and chairside polishing protocols
STATEMENT OF PROBLEM Polyetheretherketone (PEEK) can be used as a framework material for fixed dental prostheses. However, information about laboratory and chairside polishing methods is still scarce. PURPOSE The purpose of this in vitro study was to determine the effects of laboratory and chairside polishing methods on the surface roughness (SR) and surface free energy (SFE) of PEEK, an autopolymerizing poly(methyl methacrylate), and a veneering composite resin. MATERIAL AND METHODS For each of the 3 materials, 80 specimens were prepared (N=240) and divided into 7 polishing groups and 1 control group (n=10). The 7 groups were split into 4 laboratory protocols: polishing paste (Abraso), a second polishing paste (Opal L), silicone polisher (Ceragum), and diamond grinder (Diagen-Turbo grinder). The other 3 groups were chairside protocols: rainbow technique (Super-Snap kit), polishing paste (Prisma gloss), and a polishing system (Enhance finishing). Machine polishing with SiC P4000 served as the control treatment. The protocols' average SRs and SFEs were measured, and their surface topographies were evaluated with scanning electron microscopy (SEM). The logarithmically transformed data were analyzed using covariance analysis, 2-way and 1-way ANOVA, and partial correlation (α=.05). RESULTS The polishing protocol exerted the highest influence on SR and SFE values (P<.001; SR: partial eta squared ηP(2)=.970; SFE: ηP(2)=.450), followed by material group (P<.001, SR: ηP(2)=.319; SFE: ηP(2)=.429). The interaction effect of the binary combinations of the 2 independent parameters (polishing protocol and material group) was also significant (P<.001, SR: ηP(2)=.681; SFE: ηP(2)=.365). CONCLUSIONS Chairside methods presented lower SR values than laboratory methods, and specimens polished using the 2-body mode showed higher SR than did specimens polished using the 3-body mode
Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis
Most antineoplastic chemotherapies eliminate cancer cells through activation of the mitochondria-controlled intrinsic apoptotic pathway. Therein, BAX, BAK, and/or BOK function as the essential pore-forming executioners of mitochondrial outer membrane permeabilization (MOMP). The activation threshold of BAX and BAK also correlates inversely with the required strength of an apoptotic stimulus to induce MOMP and thereby effectively determines a cell's readiness to undergo apoptosis. Consequently, the 'gatekeepers' BAX and BAK emerged as therapeutic targets, but functional or genetic loss renders BAX/BAK-targeting strategies prone to fail. Here, we show that the small molecule Raptinal overcomes this limitation by triggering cytochrome c release in a BAX/BAK/BOK-independent manner. Raptinal exerts a dual cytotoxic effect on cancer cells by rapid activation of the intrinsic apoptotic pathway and simultaneous shutdown of mitochondrial function. Together with its efficacy to eliminate cancer cells in vivo, Raptinal could be useful in difficult-to-treat cancer entities harboring defects in the intrinsic apoptosis pathway
Subcellular localization of PDâL1 and cellâcycleâdependent expression of nuclear PDâL1 variants: implications for head and neck cancer cell functions and therapeutic efficacy
The programmed cell death 1 ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD-L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD-L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD-L1 in various cellular compartments of six well-characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD-L1 in its well-known glycosylated/deglycosylated state at 40â55âkDa. In addition, we detected previously unknown PD-L1 variants with a molecular weight at approximately 70 and >â150âkDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD-L1 variant expression is cell-cycle-dependent. Immunofluorescence staining of PD-L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD-L1 trafficking remain less understood; however, proximity ligation assays showed a cell-cycle-dependent interaction of the cytoskeletal protein vimentin with PD-L1, whereas vimentin could serve as a potential shuttle for nuclear PD-L1 transportation. Mass spectrometry after PD-L1 co-immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD-L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD-L1 and multiple tumor cell-intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition
Hypertonicity counteracts MCL 1 and renders BCL XL a synthetic lethal target in head and neck cancer
Head and neck squamous cell carcinoma (HNSCC) is an aggressive and difficultâtoâtreat cancer entity. Current therapies ultimately aim to activate the mitochondriaâcontrolled (intrinsic) apoptosis pathway, but complex alterations in intracellular signaling cascades and the extracellular microenvironment hamper treatment response. On the one hand, proteins of the BCLâ2 family set the threshold for cell death induction and prevent accidental cellular suicide. On the other hand, controlling a cell's readiness to die also determines whether malignant cells are sensitive or resistant to anticancer treatments. Here, we show that HNSCC cells upregulate the proapoptotic BH3âonly protein NOXA in response to hyperosmotic stress. Induction of NOXA is sufficient to counteract the antiapoptotic properties of MCLâ1 and switches HNSCC cells from dual BCLâXL/MCLâ1 protection to exclusive BCLâXL addiction. Hypertonicityâinduced functional loss of MCLâ1 renders BCLâXL a synthetically lethal target in HNSCC, and inhibition of BCLâXL efficiently kills HNSCC cells that poorly respond to conventional therapies. We identify hypertonicityâinduced upregulation of NOXA as link between osmotic pressure in the tumor environment and mitochondrial priming, which could perspectively be exploited to boost efficacy of anticancer drugs
Effect of different cleaning methods of polyetheretherketone on surface roughness and surface free energy properties
PURPOSE To determine the effect of different individual, laboratory and professional cleaning methods on the surface-roughness (SR) and surface free energy (SFE) of polyetheretherketone (PEEK), PMMA-based (PMMA) and composite (COMP) materials. METHODS 330 specimens of PEEK, PMMA and COMP (N = 990) were prepared and divided into the following cleaning protocols (n = 30/group): (i) individual prophylaxis using (ST) soft, (MT) medium-hard and (SOT) sonic toothbrushes, (ii) in-lab cleaning protocols consisting of (SY) Sympro cleaning system, (SS) SunSparkle, (UB) ultrasonic bath and (AP) Al2O3-powder device and (iii) professional prophylaxis applying (PS) Perio Soft-Scaler, (SO) Sonicsys, (AFC) Air Flow Comfort, and (AFP) Air Flow Plus. After each protocol SR (profilometer), SFE (contact angle devise) and surface topography (SEM) were measured. Data were analyzed using multivariate analysis, Kruskal-Wallis-H- and Mann-Whitney-U-test (p<0.05). RESULTS No impact of material on SR was observed (p = 0.443). Cleaning using conventional air-abrasion and powders (AP), followed by AFC produced higher SR values than the remaining methods (p<0.001). Within SFE, the cleaning method exerted the highest influence on SFE values (p<0.001, ηP2 = 0.246), closely followed by the polymer material (p<0.001, ηP2 = 0.136). PMMA and PEEK presented after cleaning lower SFE than COMP. PS, UB and SO showed lower SFE than specimens cleaned using SS, ST and SY. Cleaning using SY led to the highest SFE. CONCLUSIONS With regard to SR, all methods - with exception of conventional air-abrasion - can be recommended to clean PEEK. According to the SFE, PEEK may be an acceptable material providing even lower plaque accumulation rates than COMP. The field for more research is now open for scrutiny
Discoloration of PMMA, composite, and PEEK
INTRODUCTION To assess the discoloration and stain removal potential of different cleaning methods relevant to individual/professional prophylaxis and laboratory cleaning on polyetheretherketone (PEEK), poly(methyl methacrylate) (PMMA)-based, and composite (COMP) materials after storage in different media for 7 days. METHODS One thousand three hundred twenty specimens of PEEK, PMMA, and COMP (N = 440 of each group) were prepared and stored in four different media for 7 days to cause stain. Samples were divided into three cleaning groups (n = 10): (i) individual prophylaxis, (ii) laboratory protocols, and (iii) professional prophylaxis. Color was determined by a portable spectrophotometer and calculated between different time points (âE). The data was statistically evaluated using univariate analyses, Kruskal-Wallis H and Mann-Whitney U tests (p < 0.05). RESULTS The significantly (p < 0.001) lowest discoloration was found when specimens were stored in distilled water and chlorhexidine (CHX), followed by red wine. Curry solution caused the highest discoloration. PEEK showed the significantly (p < 0.001) lowest color changes, while COMP showed the highest changes. Ultrasonic bath and Air Flow Plus (AFP) were the significantly (p < 0.001) most effective methods to remove staining. The least cleaning effect was found using a soft toothbrush (ST), a medium-hard toothbrush (MT), and SunSparkle (SS) cleaning system. CONCLUSIONS PEEK seems more stable against discolorations than other denture resin materials. Regarding the cleaning potential, individual prophylaxis can be conducted with toothbrushes. For professional prophylaxis, air-abrasion devices using gentle powders are effective. Laboratory protocols should include gentle cleaning methods like ultrasonic bath. CLINICAL RELEVANCE Clinicians and dental technicians should inform their patients about the discoloration potential of certain foods/beverages and recommend the most efficient cleaning, but preventive methods
Hypertonicity-imposed BCL-XL addiction primes colorectal cancer cells for death
Induction of mitochondria-controlled (intrinsic) apoptosis is a mainstay of current anti-neoplastic chemotherapies. Activation of this death pathway is counteracted by BCL-2-like proteins, which functionally set the threshold for apoptosis and determine whether malignant cells are sensitive or resistant to anti-cancer treatments. Hence, unlocking the intrinsic apoptotic cascade and promoting the cell's commitment to undergo apoptosis concordantly promotes efficacy of anti-cancer treatments. Here, we show that hyperosmotic stress enforces addiction of colorectal cancer cells to BCL-XL, thereby exhausting the protective capacity of BCL-2-like proteins and priming mitochondria for death. Our work identifies osmotic pressure as a cell extrinsic factor that modulates responsiveness of colorectal cancer cells to therapy