Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IONIZATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed2001

Investigation of different combinations of derivatization, separation methods and electrospray ionization mass spectrometry for standard oligosaccharides and glycans from ovalbumin.

Derivatization procedures using 1-phenyl-3-methyl-5-pyrazolone (PMP) and 2-aminonaphthalene trisulfone (ANTS) were selected among a number of well known methods for labelling carbohydrates. PMP derivatives were selected owing to our laboratory's previous high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) experience with these, whereas the ANTS-labelled compounds were prepared for fluorophore-assisted carbohydrate electrophoresis (FACE) separation. ANTS-oligosaccharide standards were characterized to study their ionization patterns. Reversed-phase and normal-phase HPLC systems were coupled on-line with ESI-MS. Each necessitated its own mobile phase system which, in turn, imposed some important changes in the ionization conditions used and/or on the ionization patterns and spectra obtained. Following characterization of the intact glycoprotein ovalbumin with ESI-MS, its glycans were detached using the enzyme PNGase-F. The glycans were subjected to PMP and ANTS derivatization. It was very difficult to separate ANTS derivatives by reversed-phase HPLC owing to lack of retention, and normal-phase HPLC offered reasonable retention with limited separation. PMP compounds overall yielded better normal- and reversed-phase separations and improved sensitivity over the ANTS-labelled sugars, for which negative mode ESI had to be used. The combination of ESI of intact ovalbumin and ESI of PMP-glycans gave rise to the detection of over 20 different glycoforms, excluding the possible presence of structural isomers for each sugar composition detected.

Amidohydrolases↗
PubMed2003

Role of opposite charges in protein electrospray ionization mass spectrometry.

The conformation dependence of protein spectra recorded by electrospray ionization mass spectrometry (ESI-MS) is an interesting and useful phenomenon, whose origin is still the object of debate. Different mechanisms have been invoked in the attempt to explain the lower charge state of folded versus unfolded protein ions in ESI-MS, such as electrostatic repulsions, solvent accessibility, charge availability, and native-like interactions. In this work we try to subject to direct experimental test the hypothesis that conformation-dependent neutralization of charges with polarity opposite to the net charge of the protein ion could play a critical role in such an effect. We present results of time-of-flight nano-ESI-MS on the peptide angiotensin II, indicating that negative charges of carboxylate groups can contribute to spectra recorded in positive-ion mode when stabilized by favorable electrostatic interactions, which is the central assumption of our hypothesis. Comparison of horse and spermwhale myoglobin (Mb) shows that changing the total number of basic residues within a given three-dimensional structure shifts the charge-state distribution (CSD) of the folded protein in positive-ion mode. This result appears to be in contrast to models in which electrostatic repulsions or availability of charges in the ESI droplets represent the limiting factor for the ionization of folded protein ions in ESI-MS. At the same time, it suggests a role of acidic residues in conformational effects in positive-ion mode. Furthermore, an attempt is made to rationalize those cases in which, in contrast, the main charge state observed in ESI-MS under non-denaturing conditions deviates considerably from the net charge expected on the basis of the amino-acid composition. These cases usually correspond to proteins with quite balanced content in basic and acidic residues, suggesting that this might be a factor influencing their charging behavior in ESI-MS. Experiments on mutants of ribonuclease Sa (RNase Sa) reveal that progressively reducing the excess of acidic residues, replacing them by lysine, causes almost no shift in the spectrum of the folded protein in negative-ion mode. Analogously, variants with an excess of three or five basic residues give similar spectra in positive-ion mode. These results indicate a lower limit to the extent of ionization observable by ESI-MS (6- or 8+ in the case of RNase Sa in water). Below such limit of net charge, changes in the relative amount of ionizable side chains do not affect the qualitative features of the observed CSDs. A progressive loss of signal intensity caused by the mutations in negative-ion mode suggests that low charge states might also be counterselected, even within the m/z range theoretically accessible to the instrument.

Angiotensin II↗
PubMed2005

Testing the role of solvent surface tension in protein ionization by electrospray.

This work was aimed at probing the influence of solvent surface tension on protein ionization by electrospray. In particular, we were interested in testing the previously suggested hypothesis that the charge-state distributions (CSDs) of proteins in electrospray ionization mass spectrometry (ESI-MS) are controlled by the surface tension of the least volatile solvent component. In the attempt to minimize uncontrolled conformational effects, we used acid-sensitive proteins (cytochrome c and myoglobin) at low pH or highly stable proteins (ubiquitin and lysozyme) in the presence of low concentrations of organic solvents. A first set of experiments compared the effect of 1- and 2-propanol. These two alcohols have similar chemico-physical properties but values of vapor pressure below and above that of water, respectively. Both compounds have much lower surface tension than water. The solvents employed allowed testing of the influence of surface tension on protein spectra obtained from similarly denaturing solutions. The compared solvent conditions gave rise to very similar spectra for each tested protein. We then investigated the effect of the addition of dimethyl sulfoxide to acid-unfolded proteins. We observed enhanced ionization in the presence of acetic or formic acid, consistent with the previously described supercharging effect, but almost no shift of the CSD in the presence of HCl. Finally, we analyzed thermally denatured cytochrome c, to obtain reference spectra of the unfolded protein in high-surface-tension solutions. Also in this case, the CSD of the unfolded protein was shifted towards lower m/z values relative to low-surface-tension systems. In contrast to the other results reported here, this effect is consistent with an influence of solvent surface tension on CSD. The magnitude of the effect, however, is much smaller than predicted by the Rayleigh equation. The results presented here are not easy to reconcile with the hypothesis that the maximum charge state exhibited by proteins in ESI-MS reflects the Rayleigh-limit charge of the precursor droplet. The data are discussed with reference to models for the mechanism of electrospray ionization.

Ions↗
PubMed2006

Differentiation of diiodothyronines using electrospray ionization tandem mass spectrometry.

Diiodothyronines 3,5-diiodothyronine (3,5-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,3'-diiodothyronine (3,3'-T2) are important metabolites of 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3; reverse T3). In this paper, a novel and rapid method for identifying and quantifying 3,5-T2, 3',5'-T2 and 3,3'-T2 has been introduced using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Fragmentation patterns were proposed on the basis of our data obtained by ESI-MS/MS. MS2 spectra in either negative ionization mode or positive ionization mode can be used to differentiate 3,5-T2, 3',5'-T2 and 3,3'-T2. On the basis of the relative abundance of fragment ions in MS2 spectra under the positive ionization mode, quantification of the 3,5-T2, 3',5'-T2 and 3,3'-T2 isomers in mixtures is also achieved without prior separation.

Diiodothyronines↗
PubMed2006

Mass spectrometric characterization of efaproxiral (RSR13) and its implementation into doping controls using liquid chromatography-atmospheric pressure ionization-tandem mass spectrometry.

Efaproxiral (2-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxyl]-2-methylpropionic acid, formerly referred to as RSR13) is prohibited in sports according to the World Anti-Doping Agency (WADA). The drug as well as structurally related compounds and a stable isotope-labeled derivative have been synthesized to elucidate the fragmentation pathway of efaproxiral, using electrospray ionization (ESI) and tandem mass spectrometry by employing a novel linear ion trap--orbitrap hybrid mass spectrometer--in positive and negative ionization modes. The elimination of 2-methyl acrylic acid (-86 u) has been identified as a major fragmentation process in both charge states. Negative ionization and collision-induced dissociation (CID) caused an additional release of carbon dioxide (-44 u), and positive ionization the loss of formic acid (-46 u). Efaproxiral was incorporated into an existing screening procedure for doping controls using solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry, enabling a limit of detection of 2.5 ng/ml and interday precisions ranging from 7.9 to 13.0%.

Aniline Compounds↗
PubMed2003

Sonic spray ionization applied to liquid chromatography/mass spectrometry analysis of endocrine-disrupting chemicals in environmental water samples.

A sonic spray ionization liquid chromatography/mass spectrometry (LC/SSI-MS) procedure combined with off-line solid-phase extraction was optimized for the analysis of 20 endocrine-disrupting chemicals (EDCs) in water samples. Method development included a comparison of the novel sonic spray ionization (SSI) with more traditional ion sources, i.e. pneumatically assisted electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). It was demonstrated that SSI and ESI spectra were very similar, but were more prone to the formation of solvent cluster ions as compared with APCI spectra. This phenomenon was most prominent for SSI and resulted in an increased chemical background in full-scan mass spectra. However, this chemical noise did not affect the overall sensitivity of SSI and ESI. After optimization of LC and MS parameters, the LC/SSI-MS method was validated. Recoveries ranged from 76.3 up to 113.4% for all compounds. Limits of detection (LOD) and quantitation (LOQ) were established between 3.0 and 11.5 ng/L and 9.9 and 38.0 ng/L, respectively. Within-day (n = 5) and between-day (n = 5) reproducibility were investigated at three levels and ranged from 3.3-16.5% and 7.6-19.2%, respectively. Eight-point calibration curves were established and showed linearity for all compounds (r(2) > 0.987) over a linear dynamic range of 10-10 000 ng/L.

Chromatography, Liquid↗
PubMed2004

Analysis of derivatized and underivatized theanine enantiomers by high-performance liquid chromatography/atmospheric pressure ionization-mass spectrometry.

Theanine, a naturally occurring non-proteinic amino acid found in tea leaves, has demonstrated wide-ranging physiological activity, from lowering blood pressure to enhancing the anti-tumor activity of chemotherapeutic drugs. The chiral nature of theanine suggests that enantiospecificity plays a significant role in its various pharmacological functions. Using the Chirobiotic T (teicoplanin) chiral stationary phase, native and derivatized theanine enantiomers were separated and detected via high-performance liquid chromatography (HPLC) coupled to atmospheric pressure ionization mass spectrometry (API-MS). With the use of flow rates compatible with each ionization source, native theanine standards achieved excellent sensitivity and detection limits (10 ng/mL) for both atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). Optimum sensitivity and detection limits for derivatized theanine standards were achieved using ESI-MS. The enantiomeric composition of six commercially available L-theanine samples was evaluated using the high-flow APCI-MS method and confirmed with photodiode array detection. Five of the six products contained significant amounts of D-theanine. Only one product, SunTheanine, appeared to contain only the L-theanine enantiomer.

Adjuvants, Pharmaceutic↗
PubMed2004

Surface-activated chemical ionization ion trap mass spectrometry in the analysis of amphetamines in diluted urine samples.

A new ionization method, named surface-activated chemical ionization (SACI), was employed for the analysis of five amphetamines (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDE), amphetamine and methamphetamine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) using the same instrument, clearly showing that SACI is the most sensitive of the three. The limit of detection and linearity range for SACI were compared with those obtained using APCI and ESI, showing that the new SACI approach provides the best results for both criteria. SACI was used to analyze MDA, MDMA MDE, amphetamine and methamphetamine in four urine samples, and the quantitation results are compared with those achieved using ESI.

Amphetamines↗
PubMed2006

Analysis of triacetone triperoxide by gas chromatography/mass spectrometry and gas chromatography/tandem mass spectrometry by electron and chemical ionization.

The explosive triacetone triperoxide (TATP) has been analyzed by gas chromatography/mass spectrometry (GC/MS) and sub-nanogram detection limits are reported by ammonia positive ion chemical ionization (PICI), electron ionization (EI) and methane negative ion chemical ionization (NICI). Analysis by methane PICI and ammonia NICI gave detection limits in the low nanogram range. Analyses were carried out on (linear) quadrupole and ion trap instruments. Analysis of TATP by PICI using ammonia reagent gas is the preferred analytical method, producing low limits of detection as well as an abundant (greater than 60% of base peak) diagnostic adduct ion at m/z 240 corresponding to [TATP + NH4]+. Isolation of the [TATP + NH4]+ ion with subsequent collision-induced dissociation (CID) produces extremely low abundance product ions at m/z values greater than 60, and the m/z 223 ion corresponding to [TATP + H]+ was not observed. Density functional theory (DFT) calculations at the B88LYP/DVZP level indicate that dissociation of the complex to form NH4+ and TATP occurs at energies lower than peroxide bond dissociation, while protonation of TATP leads to cleavage of the ring structure. These results provide a method for pico-gram detection levels of TATP using commercial instrumentation commonly available in forensic laboratories. As a point of comparison, a detection limit of 15 ng was obtained by flame ionization detection.

Forensic Sciences↗
PubMed2006

New possibilities of matrix-assisted laser desorption ionization time of flight mass spectrometry to analyze barley malt quality. Highly sensitive detection of mycotoxins.

The occurrence of mycotoxins in agricultural commodities is a major health concern for livestock, humans, and the environment. Barley and subsequently malt quality is of fundamental importance to obtain good quality beer. Classical methods of analysis often require tedious, laborious, and expensive processes. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) instrumentation enables highly sensitive and fast analysis and/or detection using a very small sample. The possibilities of MALDI-TOF MS for he identification and/or detection of trichothecene mycotoxins (deoxynivalenol (DON) and nivalenol (NIV), respectively) in barley malt were examined, and it was found that almost all classical MALDI matrices failed to ionize the compounds being studied. This detailed study of the ionization conditions and the search for unconventional matrices led to the discovery of suitable MALDI matrices, which enable ionization of trichothecene mycotoxins. These were: fine powdered synthetic diamond, sodium azide, or hydrazine hydrate. It is possible to detect 8.5 x 10(-12) mol (2.5 ng) of deoxynivalenol or 64 x 10(-12) mol (20 ng) of nivalenol in just 1 microL of barley malt extract (equivalent to 600 microg of DON in 1 kg of barley malt). The procedure developed enables fast determination of DON and NIV in barley, malt, or similar products.

Beer↗
PubMed1996

Spontaneous p53 mutation in murine mesothelial cells: increased sensitivity to DNA damage induced by asbestos and ionizing radiation.

The p53 gene regulates the G1 cell cycle checkpoint in response to DNA damage. A primary murine mesothelial cell line (D9) spontaneously acquired a point mutation at codon 135 in exon 5 of the p53 gene, resulting in substitution of alanine for proline; early passage D9 cells expressed wild-type p53. The growth rate of late passage D9 cells that acquired the p53 mutation was increased compared to that of early passage cells; however, this mutation was not sufficient to confer tumorigenicity to this cell line. Mammalian cells that express wild-type p53 show a transient arrest in G1 after exposure to ionizing radiation. Early passage D9 cells showed a G1 arrest following ionizing radiation, while late passage D9 cells arrested in G2 or mitosis. The clastogenic effects of ionizing radiation can be demonstrated by the cytokinesis-arrested micronucleus assay. Following treatment with cytochalasin B to arrest cytokinesis, ionizing radiation induced micronuclei in 50% of late passage D9 cells compared to 15% of early passage cells. After exposure to 15 micrograms/cm2 of crocidolite asbestos fibers, 18% of late passage cells had micronuclei compared to 4% of early passage cells. It is hypothesized that loss of the G1 cell cycle checkpoint contributes to genetic instability in murine mesothelial cells.

Animals↗
PubMed2006

Effects of ionizing radiation on cellular structures, induced instability and carcinogenesis.

Ionizing radiation is perhaps the most extensively studied human carcinogen. There have been a number of epidemiological studies on human populations exposed to radiation for medical or occupational reasons, as a result of protracted environmental exposures due to radiation accidents, or after atomic bombings. As a result of these studies exposure to ionizing radiation has been unambiguously linked to cancer causation. While cancer induction is the primary concern and the most important somatic effect of exposure to ionizing radiation, potential health risks do not only involve neoplastic diseases but also somatic mutations that might contribute to birth defects and ocular maladies, and heritable mutations that might impact on disease risks in future generations. Consequantly it is important we understand the long-term health risks associated with exposure to ionizing radiation.

Cell Transformation, Neoplastic↗
PubMed1994

Ionizing radiation and breast cancer in men (United States).

The purposes of this study were to determine whether exposure of the vestigial male breast to ionizing radiation is associated with an increase in risk of breast cancer and, if so, to determine whether the apparent effects on risk in men are similar to those reported for women. A population-based case-control study of breast cancer in men was conducted in 10 geographic areas of the United States. Information on possible prior exposure to ionizing radiation, and on other potential risk factors for breast cancer, was obtained from personal interviews of 227 cases and 300 controls who were recruited from October 1983 to September 1986. Evidence from this study that ionizing radiation can cause breast cancer in men includes: a modest trend of increasing risk with frequency of chest X-rays; an increase in risk in men with three or more radiographic examinations, especially if received prior to 1963; and an increase in risk in men who received X-ray treatments to the chest and adjacent body areas. Risk was increased only from 20 to 35 years after initial exposure from either radiographic examinations or X-ray treatments, and declined after three to four decades since last exposure, suggesting a wave of increased risk of finite duration following exposure. The doses of radiation received could not be estimated precisely, but those from diagnostic procedures were likely similar to those received by prepubertal females in prior studies, and the results of those and the present investigation are compatible. The carcinogenic effects of ionizing radiation may be similar in the male and prepubertal female breast.

Breast Neoplasms↗
PubMed2005

Low-dose ionizing radiation: induction of differential intracellular signalling possibly affecting intercellular communication.

Given the complexity of the carcinogenic process and the lack of any mechanistic understanding of how ionizing radiation at low-level exposures affects the multistage, multimechanism processes of carcinogenesis, it is imperative that concepts and paradigms be reexamined when extrapolating from high dose to low dose. Any health effect directly linked to low-dose radiation exposure must have molecular/biochemical and biological bases. On the other hand, demonstrating some molecular/biochemical or cellular effect, using surrogate systems for the human being, does not necessarily imply a corresponding health effect. Given the general acceptance of an extrapolated LNT model, our current understanding of carcinogenesis cries out for a resolution of a real problem. How can a low-level acute, or even a chronic, exposure of ionizing radiation bring about all the different mechanisms (mutagenic, cytotoxic, and epigenetic) and genotypic/phenotypic changes needed to convert normal cells to an invasive, malignant cell, given all the protective, repair, and suppressive systems known to exist in the human body? Until recently, the prevailing paradigm that ionizing radiation brings about cancer primarily by DNA damage and its conversion to gene and chromosomal mutations, drove our interpretation of radiation carcinogenesis. Today, our knowledge includes the facts both that epigenetic events play a major role in carcinogenesis and that low-dose radiation can also induce epigenetic events in and between cells in tissues. This challenges any simple extrapolation of the LNT model. Although a recent delineation of "hallmarks" of the cancer process has helped to focus on how ionizing radiation might contribute to the induction of cancers, several other hallmarks, previously ignored--namely, the stem cells in tissues as targets for carcinogenesis and the role of cell-cell communication processes in modulating the radiation effects on the target cell--must be considered, particularly for the adaptive response, bystander effects, and genomic instability phenomena.

Bystander Effect↗
PubMedDate not supplied

Cataracts induced by microwave and ionizing radiation.

Microwaves most commonly cause anterior and/or posterior subcapsular lenticular opacities in experimental animals and, as shown in epidemiologic studies and case reports, in human subjects. The formation of cataracts seems to be related directly to the power of the microwave and the duration of exposure. The mechanism of cataractogenesis includes deformation of heat-labile enzymes, such as glutathione peroxide, that ordinarily protect lens cell proteins and membrane lipids from oxidative damage. Oxidation of protein sulfhydryl groups and the formation of high-molecular-weight aggregates cause local variations in the orderly structure of the lens cells. An alternative mechanism is thermoelastic expansion through which pressure waves in the aqueous humor cause direct physical damage to the lens cells. Cataracts induced by ionizing radiation (e.g., X-rays and gamma rays) usually are observed in the posterior region of the lens, often in the form of a posterior subcapsular cataract. Increasing the dose of ionizing radiation causes increasing opacification of the lens, which appears after a decreasing latency period. Like cataract formation by microwaves, cataractogenesis induced by ionizing radiation is associated with damage to the lens cell membrane. Another possible mechanism is damage to lens cell DNA, with decreases in the production of protective enzymes and in sulfur-sulfur bond formation, and with altered protein concentrations. Until further definitive conclusions about the mechanisms of microwaves and ionizing radiation induced cataracts are reached, and alternative protective measures are found, one can only recommend mechanical shielding from these radiations to minimize the possibility of development of radiation-induced cataracts.

Animals↗
PubMed2005

Detection and quantification of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine by electrospray ionization tandem mass spectrometry.

A novel and rapid method for identifying and quantifying 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3; reverse T3) has been introduced using electrospray ionization tandem mass spectrometry (ESI-MS/MS). MS(2) spectra in either negative ionization mode or positive ionization mode can be used to differentiate T3 and rT3. Quantification of the T3 and rT3 isomers under the negative ionization mode is also achieved without prior separation by HPLC.

Algorithms↗
PubMed2004

Spectrum of chromosomal aberrations in peripheral lymphocytes of hospital workers occupationally exposed to low doses of ionizing radiation.

Chromosome aberrations frequency was estimated in peripheral lymphocytes from hospital workers occupationally exposed to low levels of ionizing radiation and controls. Chromosome aberrations yield was analyzed by considering the effects of dose equivalent of ionizing radiation over time, and of confounding factors, such as age, gender and smoking status. Frequencies of aberrant cells and chromosome breaks were higher in exposed workers than in controls (P = 0.007, and P = 0.001, respectively). Seven dicentric aberrations were detected in the exposed group and only three in controls, but the mean frequencies were not significantly different. The dose equivalent to whole body of ionizing radiation (Hwb) did appear to influence the spectrum of chromosomal aberrations when the exposed workers were subdivided by a cut off at 50 mSv. The frequencies of chromosome breaks in both subgroups of workers were significantly higher than in controls (< or =50 mSv, P = 0.041; >50 mSv, P = 0.018). On the other hand, the frequency of chromatid breaks observed in workers with Hwb >50 mSv was significantly higher than in controls (P = 0.015) or workers with Hwb < or =50 mSv (P = 0.046). Regarding the influence of confounding factors on genetic damage, smoking status and female gender seem to influence the increase in chromosome aberration frequencies in the study population. Overall, these results suggested that chromosome breaks might provide a good marker for assessing genetic damage in populations exposed to low levels of ionizing radiation.

Adult↗
PubMed2001

Ionizing radiation can overcome resistance to TRAIL in TRAIL-resistant cancer cells.

Although the majority of cancer cells are killed by TRAIL (tumor necrosis factor-related apoptosis-inducing ligand treatment), certain types show resistance to it. Ionizing radiation also induces cell death in cancer cells and may share common intracellular pathways with TRAIL leading to apoptosis. In the present study, we examined whether ionizing radiation could overcome TRAIL resistance in the variant Jurkat clones. We first selected TRAIL-resistant or -sensitive Jurkat clones and examined cross-responsiveness of the clones between TRAIL and radiation. Treatment with gamma-radiation induced significant apoptosis in all the clones, indicating that there seemed to be no cross-resistance between TRAIL and radiation. Combined treatment of radiation with TRAIL synergistically enhanced killing of TRAIL-resistant cells, compared to TRAIL or radiation alone. Apoptosis induced by combined treatment of TRAIL and radiation in TRAIL-resistant cells was associated with cleavage of caspase-8 and the proapoptotic Bid protein, resulting in the activation of caspase-9 and caspase-3. No changes in the expressions of TRAIL receptors (DR4 and DR5) and Bcl-2 or Bax were found after treatment. The caspase inhibitor z-VAD-fmk completely counteracted the synergistic cell killing induced by combined treatment of TRAIL and gamma-radiation. These results demonstrated that ionizing radiation in combination with TRAIL could overcome resistance to TRAIL in TRAIL-resistant cells through TRAIL receptor-independent synergistic activation of the cascades of the caspase-8 pathway, suggesting a potential clinical application of combination treatment of TRAIL and ionizing radiation to TRAIL-resistant cancer cells.

Apoptosis↗