Angiopep-2-conjugated FeTi@Au core-shell nanoparticles for tumor targeted dual-mode magnetic resonance imaging and hyperthermic glioma therapy.

Herein, we fabricated gold surface-coated iron titanium core-shell (FeTi@Au) nanoparticles (NPs) with conjugation of angiopep-2 (ANG) (FeTi@Au-ANG) NPs for targeted delivery and improved NPs penetration by receptor-mediated endocytosis to achieve hyperthermic treatment of gliomas. The synthesized "core-shell" FeTi@Au-ANG NPs exhibited spherical in shape with around 16 nm particle size and increased temperature upon alternating magnetic field (AMF) stimulation, rendering them effective for localized hyperthermic therapy of cancer cells. Effective targeted delivery of FeTi@Au-ANG NPs was demonstrated in vitro by improved transport and cellular uptake, and increased apoptosis in glioma cells (C6) compared with normal fibroblast cells (L929). FeTi@Au-ANG NPs exhibited higher deposition in brain tissues and a superior therapeutic effect in an orthotopic intracranial xenograft mouse model. Taken together, our data indicate that FeTi@Au-ANG NPs hold significant promise as a targeted delivery strategy for glioma treatment using hyperthermia.

Using a consensus acupoints regimen to explore the relationship between acupuncture sensation and lumbar spinal postoperative analgesia: A retrospective analysis of prospective clinical cooperation.

OBJECTIVE: This study evaluated the effectiveness of acupuncture treatment on postoperative pain in patients with degenerative lumbar spine disease, and explored the relationship between the postoperative analgesic effect of acupuncture and the sensation of acupuncture experienced by the patients. METHODS: This retrospective study analyzed the medical records of 97 patients who had undergone an operation by the same surgeon due to degenerative lumbar disease. These patients were divided into acupuncture group (n = 32), patient-controlled analgesia (PCA) group (n = 27), and oral analgesia group (n = 38) according to the different postoperative analgesic methods. During their hospitalization, patients completed daily evaluations of their pain using a visual analogue scale (VAS), and injection times of supplemental meperidine were recorded. Also, the Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) was used in the acupuncture group. RESULTS: Each of the three treatment groups showed significant reductions in postoperative pain, as shown by reduced VAS scores. The acupuncture group, however, had less rebound pain (P < 0.05) than the other two groups. Both the acupuncture and PCA groups experienced acute analgesic effects that were superior to those in the oral analgesia group. In addition, the higher the C-MASS index on the second day after surgery, the lower the VAS score on the fourth day after surgery. There was also a significant difference in the "dull pain" in the acupuncture sensation. CONCLUSION: The results demonstrated that acupuncture was beneficial for postoperative pain and discomfort after simple surgery for degenerative spinal disease. It is worth noting that there was a disproportionate relevance between the patient's acupuncture sensation and the improvement of pain VAS score.

Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/ß-NF-κB and Keap1-Nrf2 Signalling Pathways.

Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne, a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5-15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/ß and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/ß or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.

Using a consensus acupoints regimen to explore the relationship between acupuncture sensation and lumbar spinal postoperative analgesia: A retrospective analysis of prospective clinical cooperation / 中西医结合学报

OBJECTIVE@#This study evaluated the effectiveness of acupuncture treatment on postoperative pain in patients with degenerative lumbar spine disease, and explored the relationship between the postoperative analgesic effect of acupuncture and the sensation of acupuncture experienced by the patients.@*METHODS@#This retrospective study analyzed the medical records of 97 patients who had undergone an operation by the same surgeon due to degenerative lumbar disease. These patients were divided into acupuncture group (n = 32), patient-controlled analgesia (PCA) group (n = 27), and oral analgesia group (n = 38) according to the different postoperative analgesic methods. During their hospitalization, patients completed daily evaluations of their pain using a visual analogue scale (VAS), and injection times of supplemental meperidine were recorded. Also, the Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) was used in the acupuncture group.@*RESULTS@#Each of the three treatment groups showed significant reductions in postoperative pain, as shown by reduced VAS scores. The acupuncture group, however, had less rebound pain (P < 0.05) than the other two groups. Both the acupuncture and PCA groups experienced acute analgesic effects that were superior to those in the oral analgesia group. In addition, the higher the C-MASS index on the second day after surgery, the lower the VAS score on the fourth day after surgery. There was also a significant difference in the "dull pain" in the acupuncture sensation.@*CONCLUSION@#The results demonstrated that acupuncture was beneficial for postoperative pain and discomfort after simple surgery for degenerative spinal disease. It is worth noting that there was a disproportionate relevance between the patient's acupuncture sensation and the improvement of pain VAS score.

Ligand fishing based on cell surface display of enzymes for inhibitor screening.

Ligand fishing for screening of enzyme inhibitors from complex chemical systems using baits prepared by cell surface display of the enzyme is herein demonstrated for the first time. Tyrosine phosphatase 1B (PTP1B), used as a model enzyme in this work, is displayed on the surface of E. coli cells by using ice nucleation protein (INP) as the anchoring motif. Infusion of PTP1B is characterized by western blot, immunofluorescence, proteinase K accessibility, and enzyme activity assays. Surface displayed PTP1B exhibits a maximum of 5.62 ± 0.251 U/OD600 enzymatic activity and a better stability compared with free enzyme. PTP1B displayed cells are used as solid-phase extraction adsorbent in combination with HPLC-MS to screen the inhibitors from the extracts of Rhodiola rosea, a traditional Chinese medicinal plant. Among many well-known active ingredients only arbutin is fished out with an IC50 value of 20.5 ± 0.873 µM, showing the inhibitor screening is highly selective. Furthermore, the equilibrium dissociation constant (KD) of the complex of arbutin and PTP1B was determined to be 79.6 µM by localized surface plasma resonance (LSPR) assay. The proposed ligand fishing technique using recombinant cells as baits opens a new avenue for screening of active compounds from natural products with accuracy and specificity.

The Antithrombotic Effects of Low Molecular Weight Fragment from Enzymatically Modified of Laminaria Japonica Polysaccharide.

BACKGROUND Laminaria japonica polysaccharide (LJP), a fucose enriched sulfated polysaccharide has been demonstrated to have excellent anticoagulant and antithrombotic activities. However, the antithrombotic effect of low molecular weight polysaccharide from enzymatically modified of LJP (LMWEP) remains unknown. MATERIAL AND METHODS LMWEP was prepared by fucoidanase enzymatic hydrolysis, and the antithrombotic and anticoagulant activities, and the underlying mechanism were investigated thoroughly. Rats were randomly divided into 6 groups (8 rats in each group): the blank control group, the blank control group treated with LMWEP (20 mg/kg), the model group, the model group treated with heparin (2 mg/kg), the model group treated with LJP (20 mg/kg), and the model group treated with LMWEP (20 mg/kg). After 7 days of intravenous administration, blood was collected for biochemical parameters examinations. RESULTS LMWEP increased the activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), 6-keto prostaglandin F1alpha (6-Keto-PGF1alpha), and endothelial nitric oxide synthase (eNOS). In addition, LMWEP decreased fibrinogen (FIB), endothelin-1 (ET-1), thromboxane B2 (TXB2), erythrocyte sedimentation rate (ESR), and hematocrit (HCT). CONCLUSIONS LMWEP, an enzymatically modified fragment with a molecular weight of 25.8 kDa, is a potential antithrombotic candidate for treatment of thrombosis related diseases.

Heterogeneity of Microglia Phenotypes: Developmental, Functional and Some Therapeutic Considerations.

BACKGROUND: Microglia play a pivotal role in maintaining homeostasis in complex brain environment. They first exist as amoeboid microglial cells (AMCs) in the developing brain, but with brain maturation, they transform into ramified microglial cells (RMCs). In pathological conditions, microglia are activated and have been classified into M1 and M2 phenotypes. The roles of AMCs, RMCs and M1/M2 microglia phenotypes especially in pathological conditions have been the focus of many recent studies. METHODS: Here, we review the early development of the AMCs and RMCs and discuss their specific functions with reference to their anatomic locations, immunochemical coding etc. M1 and M2 microglia phenotypes in different neuropathological conditions are also reviewed. RESULTS: Activated microglia are engaged in phagocytosis, production of proinflammatory mediators, trophic factors and synaptogenesis etc. Prolonged microglia activation, however, can cause damage to neurons and oligodendrocytes. The M1 and M2 phenotypes featured prominently in pathological conditions are discussed in depth. Experimental evidence suggests that microglia phenotype is being modulated by multiple factors including external and internal stimuli, local demands, epigenetic regulation, and herbal compounds. CONCLUSION: Prevailing views converge that M2 polarization is neuroprotective. Thus, proper therapeutic designs including the use of anti-inflammatory drugs, herbal agents may be beneficial in suppression of microglial activation, especially M1 phenotype, for amelioration of neuroinflammation in different neuropathological conditions. Finally, recent development of radioligands targeting 18 kDa translocator protein (TSPO) in activated microglia may hold great promises clinically for early detection of brain lesion with the positron emission tomography.

Honokiol Induces Autophagic Apoptosis in Neuroblastoma Cells through a P53-Dependent Pathway.

In children, neuroblastomas are the most common and deadly solid tumor. Our previous studies showed that honokiol can cross the blood-brain barrier and kill neuroblastoma cells. In this study, we further evaluated if exposure to honokiol for short periods could induce autophagy and subsequent apoptosis of neuroblastoma cells and possible mechanisms. Exposure of neuroblastoma neuro-2a cells to honokiol for 24 h induced morphological shrinkage and cell death. As to the mechanisms, honokiol consecutively induced cytochrome c release from mitochondria, caspase-3 activation, DNA fragmentation and cell apoptosis. Separately, honokiol time-dependently augmented the proportion of autophagic cells and the ratio of light chain 3 (LC3)-II/LC3-I. Pretreatment of neuro-2a cells with 3-methyladenine, an inhibitor of autophagy, attenuated honokiol-induced cell autophagy, caspase-3 activation, DNA damage and cell apoptosis. In contrast, stimulation of autophagy by rapamycin, an inducer of autophagy, significantly enhanced honokiol-induced cell apoptosis. Furthermore, honokiol-induced autophagic apoptosis was confirmed in neuroblastoma NB41A3 cells. Knocking down translation of p53 using RNA interference attenuated honokiol-induced autophagy and apoptosis in neuro-2a and NB41A3 cells. Taken together, this study showed that at early periods, honokiol can induce autophagic apoptosis of neuroblastoma cells through activating a p53-dependent mechanism. Consequently, honokiol has the potential to be a therapeutic option for neuroblastomas.

Therapeutic effects of herbal compounds in cerebral ischemia with special reference to suppression of microglia activation implicated in neurodegeneration.

Cerebral ischemia affects many especially with the ageing population. The ensuing ischemic reactions include oxidative stress, inflammation, and excitotoxicity among others. In the search for effective therapeutic strategies for cerebral ischemia, activated microglia which are the key player in neuroinflammation are now recognized as a potential therapeutic target. Microglia possess both neurotoxic and neuroprotective roles. They are protective by continuously surveilling the microenvironment, phagocytosing dead cells, secreting trophic factors and sculpting the neuronal connections by removing axons and pruning excess synapses. On the other hand, hyperactivated microglia may impair cerebral oxidative metabolism, and produce excessive proinflammatory mediators that may exacerbate the brain damage. In view of this, suppression of microglial activation has been considered a therapeutic strategy to mitigate microglia-based neuroinflammation in cerebral ischemia. However, balancing the neuroprotective and neurotoxic roles of activated microglia remains a challenging issue. Many traditional Chinese herbal agents have been used in clinic for treatment of cerebral ischemia. Here, we provide an overview of five common Chinese herbs targeting specifically microglia-mediated neuroinflammation in cerebral ischemia. It is hoped that a common parallel may be drawn from their beneficial effects especially in the latter pathological conditions for their better and effective use in the future.

Scutellarin Attenuates Microglia-Mediated Neuroinflammation and Promotes Astrogliosis in Cerebral Ischemia - A Therapeutic Consideration.

Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia, which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions. Here, we review the roles of activated microglia and reactive astrocytes in brain diseases with special reference to cerebral ischemia, and the effects of scutellarin, a Chinese herbal extract on both glial cells. We first reviewed the close spatial relation between activated microglia and reactive astrocytes as it suggests that both glial cells work in concert for tissue reconstruction and repair. Secondly, we have identified scutellarin as a putative therapeutic agent as it has been found to not only suppress microglial activation thus ameliorating neuroinflammation, but also enhance astrocytic reaction. In the latter, scutellarin amplified the astrocytic reaction by upregulating the expression of neurotrophic factors among others thus indicating its neuroprotective role. Remarkably, the effects of scutellarin on reactive astrocytes were mediated by activated microglia supporting a functional "cross-talk" between the two glial types. This review highlights some of our recent findings taking into consideration of others demonstrating the beneficial effects of scutellarin on both glial cell types in cerebral ischemia as manifested by improvement of neurological functions.

Scutellarin as a Potential Therapeutic Agent for Microglia-Mediated Neuroinflammation in Cerebral Ischemia.

The cerebral ischemia is one of the most common diseases in the central nervous system that causes progressive disability or even death. In this connection, the inflammatory response mediated by the activated microglia is believed to play a central role in this pathogenesis. In the event of brain injury, activated microglia can clear the cellular debris and invading pathogens, release neurotrophic factors, etc., but in chronic activation microglia may cause neuronal death through the release of excessive inflammatory mediators. Therefore, suppression of microglial over-reaction and microglia-mediated neuroinflammation is deemed to be a therapeutic strategy of choice for cerebral ischemic damage. In the search for potential herbal extracts that are endowed with the property in suppressing the microglial activation and amelioration of neuroinflammation, attention has recently been drawn to scutellarin, a Chinese herbal extract. Here, we review the roles of activated microglia and the effects of scutellarin on activated microglia in pathological conditions especially in ischemic stroke. We have further extended the investigation with special reference to the effects of scutellarin on Notch signaling, one of the several signaling pathways known to be involved in microglial activation. Furthermore, in light of our recent experimental evidence that activated microglia can regulate astrogliosis, an interglial "cross-talk" that was amplified by scutellarin, it is suggested that in designing of a more effective therapeutic strategy for clinical management of cerebral ischemia both glial types should be considered collectively.

Pyrone derivatives from the endophytic fungus Alternaria tenuissima SP-07 of Chinese herbal medicine Salvia przewalskii.

Three new pyrones, solanapyrones P-R (1-3), were afforded by the extracts of the endophytic fungus Alternaria tenuissima SP-07 isolated from the fresh root of Chinese herbal medicine Salvia przewalskii, along with the known solanapyrones (4-6) and benzopyrones (7-9). Solanapyrones P (1) and Q (2) possess an unprecedented nor-solanapyrone skeleton as natural products. Their structures were determined on the basis of NMR and HR-ESI-MS analysis. The plausible biosynthetic pathways to those unknown compounds were discussed. All the isolated compounds were evaluated for their antibacterial activities against six bacteria.

Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3ß,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19).

Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds-trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3ß,5α,8α-triol (SA-48)-were found to potently inhibit estrogen biosynthesis (IC50: 1µM and 0.5µM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers.

¹H nuclear magnetic resonance based-metabolomic characterization of Peucedani Radix and simultaneous determination of praeruptorin A and praeruptorin B.

As a widely used traditional herbal medicine, it is crucial to characterize the holistic metabolic profile of Peucedani Radix (Chinese name: Qian-hu). However, it is quite arduous to obtain the whole picture of chemical constituents appropriately with the existing analytical techniques that were based on HPLC-UV or LC-MS/MS system. In present investigation, nuclear magnetic resonance (NMR) spectroscopy coupled with principal components analysis (PCA) was introduced to metabolomic characterization of Qian-hu crude extracts without any chromatographic separation. In addition, the contents of praeruptorin A (PA) and proaeruptorin B (PB) in Qian-hu were simultaneously determined using quantitative (1)H NMR (q(1)H NMR) spectroscopy. Eighteen reference compounds (1-18), which were purified from this herbal drug extract previously, were recruited for the assignment of the protonic signals in the (1)H NMR spectra. Following PCA, 15 batches of Peucedani Radix were divided into two groups (I and II), and angular-type pyranocoumarins, in particular PA and PB, as well as 5-methoxycoumarin were demonstrated as the predominant markers being responsible for the distinguishment of Qian-hu from different districts. The contents of the two analytes (PA & PB) were calculated by the relative ratio of the integral values of the target peak for each compound to the known amount of the internal standard, formononetin (IS). The lower limits of quantitation were determined as 19.5µg/mL for both PA and PB. The quantitative results indicated that the contents of PA and PB showed quite variable qualities among different extract samples. Above all, (1)H NMR spectroscopy, that could not only provide comprehensive profiles of the metabolites but also achieve convenient determination of praeruptorin A and praeruptorin B, is a promising means for evaluating the medicinal samples of Peucedani Radix.

Metabolic differentiations of Pueraria lobata and Pueraria thomsonii using ¹H NMR spectroscopy and multivariate statistical analysis.

Puerariae Radix was a widely used herbal medicine. Pueraria lobata (PL) and Pueraria thomsonii (PT) were the two authorized sources of Puerariae Radix (gegen) in China. In this study, metabolic differentiations between these two species were investigated using NMR spectroscopy followed by principal components analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The content of puerarin in PL and PT was also determined using quantitative (1)H NMR spectroscopy. Thirteen isoflavones were tentatively identified based on 1D and 2D NMR spectroscopic data in two species. The (1)H NMR spectra of PL and PT were obviously different. PL and PT could also be markedly discriminated from (1)H NMR spectroscopic data by PCA and PLS-DA. For the crude drug resources, isoflavones, in which puerarin is the most important one, were regarded as the reasonable markers for the discrimination of the two species. The contents of puerarin and total isoflavones in PL were quantitated much higher than those in PT. Above all, (1)H NMR spectroscopy, which can provide comprehensive profiles of the metabolites and achieve convenient determinations of puerarin and total isoflavones in a single run, is an efficient means for evaluating the medicinal samples and achieving a better quality control of Puerariae Radix.

Biodegradable drug-eluting poly[lactic-co-glycol acid] nanofibers for the sustainable delivery of vancomycin to brain tissue: in vitro and in vivo studies.

Successful treatment of a brain infection requires aspiration of the pus or excision of the abscess, followed by long-term (usually 4-8 weeks) parenteral antibiotic treatment. Local antibiotic delivery using biodegradable drug-impregnated carriers is effective in treating postoperative infections, thereby reducing the toxicity associated with parenteral antibiotic treatment and the expense involved with long-term hospitalization. We have developed vancomycin-loaded, biodegradable poly[lactic-co-glycol acid] nanofibrous membranes for the sustainable delivery of vancomycin to the brain tissue of rats by using the electrospinning technique. A high-performance liquid chromatography assay was employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the membranes. The experimental results suggested that the biodegradable nanofibers can release high concentrations of vancomycin for more than 8 weeks in the cerebral cavity of rats. Furthermore, the membranes can cover the wall of the cavity after the removal of abscess more completely and achieve better drug delivery without inducing adverse mass effects in the brain. Histological examination also showed no inflammation reaction of the brain tissues. By adopting the biodegradable, nanofibrous drug-eluting membranes, we will be able to achieve long-term deliveries of various antibiotics in the cerebral cavity to enhance the therapeutic efficacy of cerebral infections.

[Clinical observation of sorafenib monotherapy in Chinese patients with advanced hepatocellular carcinoma].

OBJECTIVE: To observe the efficacy and safety of sorafenib monotherapy in Chinese patients with advanced hepatocellular carcinoma (HCC). METHODS: Thirty-eight patients with advanced HCC of Child-Pugh status A or B were included in this study. Patients received orally administered sorafenib at a dose of 400 mg twice a day on a continuous schedule. Adverse events were documented. The efficacy and safety were evaluated every four to six weeks. RESULTS: During the treatment, partial response (PR) was observed in 1 patient (2.6%), minor response (MR) in 5 (13.2%), stable disease (SD) in 16 (42.1%), and progressive disease (PD) in 16 (42.1%), respectively. The median oral administration time of sorafenib was 180 days (range, 15-550 d), and the mean overall survival was 370 days (range, 42-562 days). The median response duration was 169 days (range, 42-426 days). The mean overall survival of 22 patients with controlled disease (PR + MR + SD) was 428 days (95% CI 330-526 days). The most frequent adverse events were dermal reaction (27 cases, 71.1%), gastrointestinal reaction (25 cases, 65.8%), and constitutional symptoms (14 cases, 36.8%). Most of the drug related adverse events were mild and easily to manage and reversible. CONCLUSION: Sorafenib monotherapy is effective and tolerable in a part of Chinese patients with advanced hepatocellular carcinoma and liver function of Child-Pugh A or B, and may prolong their survival.

High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma.

AIM: To conduct a randomized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). METHODS: From January 1993 to June 1998, 473 patients with unresectable hepatocellular carcinoma were divided into two groups: 216 patients in group A received more than 20 mL iodized oil during the first TACE treatment; 257 patients in group B received 5-15 mL iodized oil in the same way. The Child's classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment. During the TACE procedure the catheters were inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography.The anticancer drugs mixed with iodized oil (Lipiodol) were Epirubicin and Mitomycin. In group A, 112 cases received 20-29 mL Lipiodol in the first procedure, 85 cases 30-39 mL, 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B, 119 cases received 5-10 mL Lipiodol,138 cases received 11-15 mL and the average dose was 11.8 mL. RESULTS: High-dose Lipiodol chemoembolization had tolerable side effects and a little hurt to the liver function in the patients with Child's A or ICG-R15<20. But the patients with child's B or ICG-R15>20 had higher risk of liver failure after high-dose TACE. More type I and type II in CT scan after 4 weeks of TACE were seen in the patients of group A than those in the patients of group B (P<0.01). The resection rate and complete tumor necrosis rate of group A were higher than those of group B (P<0.05). The 1-,2-, 3-year survival rates of group A patients with Child's A were 79.2 , 51.8 and 34.9 , respectively, better than those of group A (P<0.001). CONCLUSION: High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor. High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose. For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20%, oily chemoembolization with 20-40 mL Lipiodol is recommended.