Platinum-based drugs and hydrogel: a promising anti-tumor combination.

Platinum-based drugs are widely used as first-line anti-tumor chemotherapy agents. However, they also have nonnegligible side effects due to the free drugs in circulation. Therefore, it is necessary to develop efficient and safe delivery systems for better tumor cell targeting. Hydrogel is a promising anti-tumor drug carrier that can form a platinum/hydrogel combination system for drug release, which has shown better anti-tumor effects in some studies. However, there is a lack of systematic summary in this field. This review aims to provide a comprehensive overview of the platinum/hydrogel combination system with the following sections: firstly, an introduction of platinum-based drugs; secondly, an analysis of the platinum/hydrogel combination system; and thirdly, a discussion of the advantages of the hydrogel-based delivery system. We hope this review can offer some insights for the development of the platinum/hydrogel combination system for better cancer therapy.

A simple method for fabricating drugs containing a cis-o-diol structure into guanosine-based supramolecular hydrogels for drug delivery.

Supramolecular hydrogels are attractive biomaterials for local drug delivery owing to their excellent self-healing, injectable, biodegradable, and biocompatible properties. However, traditional drug-loading approaches based on non-covalent encapsulation and covalent bonding have shown problems such as rapid or difficult drug release, complex reaction processes, low reaction efficiency, and decreased drug activity. Therefore, there is a need to find a simple and efficient method to load drugs into hydrogels, which possess stable drug release ability without impairing drug efficacy. In this study, we introduce dynamic borate ester bonds via a simple one-pot method to load cis-o-diol-containing drugs into guanosine (G)-based supramolecular hydrogels. The experimental results confirm that the dynamic covalent borate ester bonds are formed based on the cis-o-diol groups of the drug and the G in these hydrogels. Meanwhile, the as-prepared G-based hydrogels not only possess self-healing properties and injectability but also have satisfactory biodegradability and biocompatibility. Additionally, the drug can be released from the G-based hydrogel according to the pH-responsive cleavage of the borate ester bonds without affecting drug activity. Overall, these results indicate that the simple one-pot method of utilizing the dynamic borate bond can provide a valuable reference for the design of hydrogel dosage forms.

Injectable catechin-based supramolecular hydrogel for highly efficient application in HPV-associated OSCC.

Catechins are a group of natural polyphenols extracted from green tea. Notably, they have been proven to have excellent anti-HPV and anti-tumour properties and to be effective against some HPV-related diseases, showing great potential in the treatment of HPV-associated oral squamous cell carcinoma (HPV+ OSCC). However, the poor bioavailability, short half-lives, and stability issues of catechins hamper their clinical application. To overcome these shortcomings of catechins, we innovatively synthesised an injectable supramolecular hydrogel, namely catechin-phenylenebisboronic acid-isoguanosine (CPBisoG), with catechin (one of the simplest catechins) and isoguanosine (isoG), another natural product with self-assembly ability, via dynamic phenylborate diester bonds. The biodegradation and sustained-release time of the CPBisoG hydrogel in mice lasted up to 72 h. This supramolecular hydrogel not only functioned as a good local drug delivery platform with good stability, injectability, self-healing properties, biocompatibility, biodegradability, but also exhibited therapeutic effects toward HPV+ OSCC in vitro and in vivo. And interestingly, it also showed selective inhibition against HPV+ OSCC cells. In all, these results demonstrate that this catechin-based hydrogel could sustainedly and highly effectively treat HPV+ OSCC topically, which could also provide a promising strategy for the management of other HPV-associated diseases in the future.

Guanosine-based Hydrogel Integrating Photothermal Effect of PDA-AuNPs through Dynamic Borate Bond for Photothermal Therapy of Cancer.

Photothermal therapy (PTT) has drawn extensive attention owing to its noninvasive and great tissue penetration depth. However, the physical encapsulation of photothermal agents may lead to their rapid release. Dual-functional hydrogel systems that integrate functions and carriers can potentially solve this problem. In this work, we successfully developed a dual-functional guanosine(G)-based hydrogel integrating the photothermal effect and localized delivery by introducing dynamic borate ester utilizing the photothermal property of PDA-AuNPs and the self-assembly ability of G. Both in vitro and in vivo results confirmed that the GBPA hydrogel not only exhibited excellent photothermal toxicity, stability, injectability, and biocompatibility, but also possessed high photothermal antitumor activity. These results suggested that the GBPA hydrogel could be used as a dual-functional hydrogel integrating photothermal effect and localized delivery in one system, which would possibly provide a new opportunity for the design of new dual-functional hydrogels for highly efficient cancer therapy.

Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma.

Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via in vivo and in vitro experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.

Isorhamnetin induces the paraptotic cell death through ROS and the ERK/MAPK pathway in OSCC cells.

OBJECTIVE: There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anti-cancer effect of isorhamnetin. METHODS AND MATERIALS: Oral squamous cell carcinoma cells were treated with or without isorhamnetin. Cell proliferation, cell cycle arrest, cell migration, cell death, and the related signaling pathways were evaluated. RESULTS: The results revealed that cell proliferation was inhibited in a dose- and time-dependent manner, which was confirmed by diminished cell viability and revealed by decreased in the number of cell colonies. In addition, the cell cycle arrested in the G2/M phase, and the protein levels of cyclin B1 and CDC2 were suppressed. Moreover, the cell migration was inhibited, and the protein levels of related proteins were modulated. Furthermore, it could be observed that abundant cytoplasmic vacuoles existed which that were derived from mitochondria and the endoplasmic reticulum. It was confirmed that cell death did not result from apoptosis and may have which may be apt to paraptosis. Isorhamnetin was observed to upregulate phosphorylated ERK cascades and increase intracellular reactive oxygen species levels. CONCLUSIONS: Our study suggested that the anti-cancer effect of isorhamnetin might trigger paraptosis, which may indicate a new therapeutic approach to OSCC.

The Dual Role of Macropinocytosis in Cancers: Promoting Growth and Inducing Methuosis to Participate in Anticancer Therapies as Targets.

Macropinocytosis is an important mechanism of internalizing extracellular materials and dissolved molecules in eukaryotic cells. Macropinocytosis has a dual effect on cancer cells. On the one hand, cells expressing RAS genes (such as K-RAS, H-RAS) under the stress of nutrient deficiency can spontaneously produce constitutive macropinocytosis to promote the growth of cancer cells by internalization of extracellular nutrients (like proteins), receptors, and extracellular vesicles(EVs). On the other hand, abnormal expression of RAS genes and drug treatment (such as MOMIPP) can induce a novel cell death associated with hyperactivated macropinocytosis: methuosis. Based on the dual effect, there is immense potential for designing anticancer therapies that target macropinocytosis in cancer cells. In view of the fact that there has been little review of the dual effect of macropinocytosis in cancer cells, herein, we systematically review the general process of macropinocytosis, its specific manifestation in cancer cells, and its application in cancer treatment, including anticancer drug delivery and destruction of macropinocytosis. This review aims to serve as a reference for studying macropinocytosis in cancers and designing macropinocytosis-targeting anticancer drugs in the future.

Protective role of citric acid against oxidative stress induced by heavy metals in Caenorhabditis elegans.

The adverse effects of heavy metals, such as cadmium, zinc, and copper, occur due to the generation of reactive oxygen species (ROS). The use of Caenorhabditis elegans for the purposes of conservation and biomonitoring is of great interest. In the present study, ROS, malondialdehyde (MDA), and citric acid levels and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in a model organism were tested to study toxicity. C. elegans was exposed to three different concentrations of cadmium (CdCl2, 5, 10, 50 µM), zinc (ZnSO4, 10, 100, 500 µM), and copper (CuSO4, 10, 100, 500 µM) for 3 days. ROS levels increased by 1.3- to 2.1-fold with increasing metal concentrations. The MDA content increased by approximately 7-, 5-, 2-fold after exposure to high concentrations of cadmium, zinc, and copper, respectively. Furthermore, the citric acid content increased by approximately 3-fold in the cadmium (Cd, 5 µM), zinc (Zn, 10 µM), and copper (Cu, 100 µM) treatment groups compared to that in untreated C. elegans. Therefore, citric acid may play an important role in heavy metal detoxification. Excess citric acid also slightly increased the LC50 by 1.3- to 2.0-fold, basic movements by 1.0- to 1.5-fold, decreased the ROS content by 2.4- to 2.1-fold, the MDA content by 4- to 2-fold, the SOD activity by 9- to 3-fold, the GPx activity by 4.0- to 3.0-fold, and the mRNA expression levels of GPxs by 3.2- to 1.8-fold after metals treatment. And it is most significantly in the alleviation of citric acid to cadmium. This study not only provides information to further understand the effects of heavy metal exposure on ROS, MDA, GPx, SOD, and citric acid in worms but also indicates that supplemental citric acid can protect animals from heavy metal stress and has broad application prospects in decreasing oxidative damage caused by heavy metals.

Antioxidant enzymes and their role in phoxim and carbaryl stress in Caenorhabditis elegans.

Pesticide exposure can induce oxidative stress and cause changes to antioxidant enzymes in living organisms. In the present study, the effects of phoxim (an organophosphorus insecticide) and carbaryl (a carbamate insecticide) on antioxidant enzyme activity and gene expression were investigated in the model organism Caenorhabditis elegans. The results show that phoxim exposure can induce superoxide dismutase (SOD) and catalase (CAT) activities and decrease glutathione peroxidase (GPx) activity at lower concentrations. The expression levels of sod-3, sod-5, ctl-1, gpx-6, and gpx-8 were up-regulated after treatment with phoxim. The mRNA expression levels of sod-5, ctl-1 and gpx-6 were increased approximately 70-, 170- and 130-fold, respectively, in the 0.25mM treatment group compared to the control group. Carbaryl exposure decreased SOD activity and induced CAT and GPx activities. The addition of carbaryl up-regulated the expression of sod-5, ctl-1, ctl-3 and gpx-8. Specifically, ctl-1 expression increased approximately 10-fold, and gpx-8 expression increased <30-fold in the 0.5mM treatment group relative to the control group. The transcript level of sod-5 increased >20-fold, and ctl-3 increased approximately 10-fold in the 1mM treatment group. The functions of the antioxidant enzymes during oxidative stress caused by the two insecticides were investigated using deletion mutants. The LC50 values phoxim for the of sod-3 (tm760), sod-5 (tm1146), ctl-1 (ok1242), ctl-3 (ok2042) and gpx-8 (tm2108) mutant strains were lower than those observed for the N2 strain. The LC50 values of carbaryl for the ctl-1 (ok1242), ctl-3 (ok2042) and gpx-6 (tm2535) deletion mutant strains decreased in comparison to the N2 strain. The results suggest that these two insecticides caused oxidative stress and changed altered the antioxidant enzyme activities and their gene expressions in C. elegans. The sod-3, sod-5, ctl-1, ctl-3, gpx-6, and gpx-8 encoding enzymes may play roles in defending cells from oxidative stress caused by these two insecticides.

HBsAg seroclearance or seroconversion induced by peg-interferon alpha and lamivudine or adefovir combination therapy in chronic hepatitis B treatment: a meta-analysis and systematic review

Background and aims: Seroclearance or seroconversion of hepatitis B surface antigen (HBsAg) is generally considered as a clinical endpoint. The purpose of the present meta-analysis was to evaluate the effect of combined therapy with pegylated interferon alpha (PEG-IFNα) with or without lamivudine (LAM) or adefovir (ADV) on HBsAg seroclearance or seroconversion in subjects with chronic hepatitis B (CHB). Methods: Randomized controlled trials performed through May 30th 2015 in adults with CHB receiving PEG-IFNα and LAM or ADV combination therapy or monotherapy for 48-52 weeks were included. The Review Manager Software 5.2.0 was used for the meta-analysis. Results: No statistical differences in HBsAg seroclearance (9.9% vs. 7.1%, OR = 1.47, 95% CI: 0.75, 2.90; p = 0.26) or HBsAg seroconversion (4.2% vs. 3.7%, OR = 1.17, 95% CI: 0.57, 2.37; p = 0.67) rates were noticed between PEG-IFNα + LAM and PEG-IFN α + placebo during post-treatment follow-up for 24-26-weeks in subjects with hepatitis Be antigen (HBeAg)- positive CHB. No statistical differences in HBsAg clearance (10.5% vs. 6.4%, OR = 1.68, 95% CI: 0.75, 3.76; p = 0.21) were seen, but statistical differences in HBsAg seroconversion (6.3% vs. 0%, OR = 7.22, 95% CI: 1.23, 42.40; p = 0.03) were observed, between PEG-IFNα + ADV and PEG-IFNα for 48-52 weeks of treatment in subjects with HBeAg-positive CHB. A systematic evaluation showed no differences in HBsAg disappearance and seroconversion rates between PEG-IFNα + placebo and PEG-IFNα + LAM for 48-52 weeks in subjects with HBeAg-positive CHB. A systematic assessment found no differences in HBsAg disappearance and seroconversion rates between PEG-IFNα + placebo and PEG-IFNα + LAM during 24 weeks’ to 3 years’ followup after treatment in subjects with HBeAg-negative CHB. Conclusion: Combined therapy with PEG-IFNα and LAM or ADV was not superior to monotherapy with PEG-IFNα in terms of HBsAg seroclearance or seroconversion (AU)

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HBsAg seroclearance or seroconversion induced by peg-interferon alpha and lamivudine or adefovir combination therapy in chronic hepatitis B treatment: a meta-analysis and systematic review.

BACKGROUND AND AIMS: Seroclearance or seroconversion of hepatitis B surface antigen (HBsAg) is generally considered as the clinical endpoint. The purpose of the present meta-analysis was to evaluate pegylated interferon alpha (PEG-IFNα) with or without lamivudine (LAM) or adefovir (ADV) combination treatment in HBsAg seroclearance or seroconversion with CHB. METHODS: Randomized controlled trials of adults with CHB prior to May 30th 2015, with 48-52 weeks of PEG-IFNα and LAM or ADV combination therapy or monotherapy, were included. Review Manager Software 5.2.0 was used for meta-analysis. RESULTS: No statistical difference was noticed in HBsAg seroclearance (9.9% vs 7.1%, OR = 1.47, 95% CI 0.75, 2.90; p = 0.26) or observed in HBsAg seroconversion (4.2% vs 3.7%, OR = 1.17, 95% CI 0.57, 2.37; p = 0.67) between PEG-IFNα + LAM and PEG-IFNα + placebo for 24-26 weeks follow-up after treatment on hepatitis B e antigen (HBeAg)-positive CHB. Statistical difference was not showed in HBsAg disappearance (10.5% vs 6.4%, OR = 1.68, 95% CI 0.75, 3.76; p = 0.21) but was demonstrated in HBsAg seroconversion (6.3% vs 0%, OR = 7.22, 95% CI 1.23, 42.40; p = 0.03) between PEG-IFNα + ADV and PEG-IFNα for 48-52 weeks treatment on HBeAg-positive CHB By systematical evaluation, there were no differences in HBsAg disappearance and seroconversion between PEG-IFNα + placebo and PEG-IFNα + LAM for 48-52 weeks treatment on HBeAg-positive CHB. There were no differences in HBsAg disappearance and seroconversion between PEG-IFNα + placebo and PEG-IFNα + LAM during 24 weeks to 3 years follow-up after treatment on HBeAg-negative CHB by systematical evaluation. CONCLUSION: The combination between PEG-IFNα and LAM or ADV was not superior to monotherapy of PEG-IFNα in terms of HBsAg seroclearance or seroconversion.

ace-3 plays an important role in phoxim resistance in Caenorhabditis elegans.

Organophosphorus and carbamate are widely used in agricultural production. Caenorhabditis elegans is a model organism that is widely used in various toxicology studies. To understand the effects of two types of commonly used pesticides, phoxim (organophosphorus) and carbaryl (carbamate), we determined the activities of acetylcholinesterases (AChEs) and detected the expression of four ace genes by RT-qPCR in C. elegans following treatment with these pesticides. The results showed that phoxim and carbaryl could reduce acetylcholinesterase activities and up-regulate the ace-3 mRNA expression levels. We also detected the toxic effects of these pesticides on the ace-3 deletion mutant dc-2, and found that some characteristics, including LC50, development, movement, reproduction and lifespan, were reduced in the dc-2 mutant. However, the toxic effects of carbaryl were weaker than those of phoxim. Carbaryl treatment did not significantly affect the LC50, movement ability or lifespan. Interestingly, body and brood size increased with carbaryl treatment at low concentrations. These data showed that both phoxim and carbaryl could inhibit AChE but that the ace-3 was necessary for phoxim detoxification. The LC50 of phoxim and carbaryl in wild type N2 and the ace-3 deletion mutant dc-2. **Higher significant differences (P < 0.01).

Screening and SNP mapping of copper-resistant mutations in C. elegans.

Copper plays critical roles in biological system; however, it is toxic in excess. To identify novel genes involved in copper metabolism, we performed a whole genome-wide genetic screen in C. elegans model organism to search for mutants which are resistant to excessive copper. Wild type (N2) L4 worms were mutagenized with ethylmethane sulfonate (EMS), and the F2progeny were screened on culture medium with excess copper. Two copper-resistant mutants, ms1and ms2, were recovered from the screening of 100 000 hyploid genomes. No obvious developmental defects were observed in ms1and ms2mutants, and they were able to grow into adults on screen medium plate, but N2worms arrested in L1stage. Results of backcross test suggested that copper-resistant phenotype in ms1may be controlled by a single recessive gene, but probably there are mutations in multiple genes in ms2, as no copper resistant worms could be found in F2progeny when ms2mutants were backcrossed with N2worms. To determine the mutation positions of ms1, we employed single nucleotide polymorphisms (SNPs) mapping. Our mapping results indicated that ms1mutation is on chromosome II (LGII). By analysis of 8 SNP markers from -18 to 23 on LGII, we found that ms1mutation is at approximately LGII:-6. Further study on ms1mutants will provide insights into copper metabolism and its regulation.

Molecular basis for antioxidant enzymes in mediating copper detoxification in the nematode Caenorhabditis elegans.

Antioxidant enzymes play a major role in defending against oxidative damage by copper. However, few studies have been performed to determine which antioxidant enzymes respond to and are necessary for copper detoxification. In this study, we examined both the activities and mRNA levels of SOD, CAT, and GPX under excessive copper stress in Caenorhabditis elegans, which is a powerful model for toxicity studies. Then, taking advantage of the genetics of this model, we assessed the lethal concentration (LC50) values of copper for related mutant strains. The results showed that the SOD, CAT, and GPX activities were significantly greater in treated groups than in controls. The mRNA levels of sod-3, sod-5, ctl-1, ctl-2, and almost all gpx genes were also significantly greater in treated groups than in controls. Among tested mutants, the sod-5, ctl-1, gpx-3, gpx-4, and gpx-6 variants exhibited hypersensitivity to copper. The strains with SOD or CAT over expression were reduced sensitive to copper. Mutations in daf-2 and age-1, which are involved in the insulin/insulin-like growth factor-1 signaling pathway, result in reduced sensitivity to stress. Here, we showed that LC50 values for copper in daf-2 and age-1 mutants were significantly greater than in N2 worms. However, the LC50 values in daf-16;daf-2 and daf-16;age-1 mutants were significantly reduced than in daf-2 and age-1 mutants, implying that reduced copper sensitivity is influenced by DAF-16-related functioning. SOD, CAT, and GPX activities and the mRNA levels of the associated copper responsive genes were significantly increased in daf-2 and age-1 mutants compared to N2. Additionally, the activities of SOD, CAT, and GPX were greater in these mutants than in N2 when treated with copper. Our results not only support the theory that antioxidant enzymes play an important role in copper detoxification but also identify the response and the genes involved in these processes.

Changes to cuticle surface ultrastructure and some biological functions in the nematode Caenorhabditis elegans exposed to excessive copper.

Copper is an essential metal, but its toxic effects are pronounced when organisms are exposed to it in excessive amounts. However, information about the effects of chronic copper exposure on the cuticle ultrastructure of organisms is insufficient. Studies of the model organism, Caenorhabditis elegans, could further our understanding of the effect of chronic excessive copper exposure on human health. In this study, the cuticle surface ultrastructure of C. elegans was observed using scanning electron microscopy after excessive copper exposure. In addition to this, some biological functions, such as chemotaxis, reproduction, and development, were also analyzed. After chronic excessive copper exposure, the worms' body surface from vulva to tail was extensively wrinkled and folded along with the annulus. The worm's vulva size was significantly decreased, and the middle ridge of the alae was disrupted. Furthermore, some of the biological functions of nematodes were also affected: the chemotaxis index was partially changed, bags-of-worms were induced, development was delayed, and egg-laying number was decreased by copper treatment. The results of the present study shed new light on the effects of copper on C. elegans cuticle as well as some biological functions.

Chronic accumulation of cadmium and its effects on antioxidant enzymes and malondialdehyde in Oxya chinensis (Orthoptera: Acridoidea).

The accumulation of cadmium (Cd) and its effects on antioxidant enzyme activities and malondialdehyde (MDA) levels of Chinese rice grasshopper (Oxya chinensis) were evaluated under the laboratory conditions. Our results showed that Cd accumulation in O. chinensis exhibited a concentration-dependent increase in both males and females under Cd pollution. Environmental Cd can lead to the absorption of large quantities of Cd, which induces oxidative damage in insects by altering antioxidant defense enzyme systems. Our results demonstrated that Cd stress caused a significant decrease in glutathione peroxidase (GPx) levels and a significant increase in superoxide (SOD) dismutase and catalase (CAT) activities. In the grasshoppers, the MDA content was also enhanced, with an increase in Cd concentrations and a positive correlation between them; for females from second instar nymphs to the adult stage, R(2) was 0.6467, 0.9136, 0.6516, 0.942 and 0.7182, whereas for males, it was 0.6467, 0.8239, 0.9302, 0.7861, 0.8632, respectively. We also observed differences in the effects of Cd between grasshoppers of different developmental stages and genders, which suggested that the insect's developmental stage and sex should be considered when studying enzyme activity.

Cerebral artery evaluation of dual energy CT angiography with dual source CT.

BACKGROUND: Conventional computed tomography angiography (CTA) is time consuming, user-dependent and has poor image quality in skull base region. This study assessed the feasibility of a new method, dual energy CTA for depicting the cerebral artery. METHODS: Phantom scan was done with head CTA sequences on dual source CT and 64 spiral CT for radiation dose calculation. Dual energy CTA was done with dual source CT on 36 patients who were suspected of having cerebral vascular disease. Three series axial images in 0.75 mm thick, 0.4 mm increment were acquired, which were named with 80 kV, 140 kV and merged images; 80 kV and 140 kV images were transferred into dual energy software, and maximum intensity projection (MIP) image was generated quickly by dual energy bone remove (DEBR group); merged images were transferred into In Space software to acquire MIP image through manual conventional bone remove (CoBR group). Post processing time and reading time were compared. Image qualities of the two groups were compared, mainly focusing on skull base segments of internal carotid artery and bone subtraction. ANOVA and SNK tests were applied for radiation dose comparison. Student's t test and Wilcoxon rank sum test were applied for assessing differences between data for significance. Cohen's kappa was used for interobserver agreement. RESULTS: Radiation dose of phantom scan showed dual energy CTA was between digital bone subtraction and conventional CTA. The post processing time and reading time were much shorter in DEBR than CoBR, and image quality in skull base was much higher in DEBR than CoBR (P < 0.01). There was no significant difference for suprasellar vessels between two groups (P > 0.5). Interobserver agreement for all vessel segments was excellent (kappa = 0.97). CONCLUSIONS: Dual energy CTA is a reliable, new modality for depicting cerebral artery, overcoming the limitation of conventional CTA in the skull base region. It can save much time in post processing and reading than conventional CTA.