摘要
Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.
摘要
Cancer immunotherapy is one of the most promising biological therapies. The dynamic changes of the immune microenvironment of heterogeneous tumors are critical factors in determining the interaction and therapeutic efficacy between tumor and immune microenvironment. Therefore, quantitative analysis of its constituent cells, related genes, and phenotypes in real time is of great importance. The methods used to analyze tumor immune microenvironment include immunohistochemistry, flow cytometry and so on. With the development of next-generation sequencing technology, transcriptome RNA sequencing data analysis has become one of the important methods to determine the composition of tumor immune microenvironment. This article focuses on the common methods of bulk RNA sequencing data analysis and related research progress.
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Retrieved the literature on randomized controlled trials (RCT) of acupuncture and moxibustion from 2011 to 2020 in the Web of Science (WOS) database, and explored research hotspots and frontiers in the field of acupuncture and moxibustion by visually analyze to countries, institutions, authors, keywords, cited literature, etc. using CiteSpace V5.6.R2. A total of 1147 articles were included. China has the largest number of publications, and the top 3 publications are Beijing University of Chinese Medicine, Capital Medical University and Kyung Hee University. The hot research interventions in acupuncture and moxibustion include acupuncture, electroacupuncture, and bee acupuncture. The hot research topics include nerve regeneration, spasms, nausea, pain, obesity, cancer, etc. The research frontiers include acupuncture analgesia, diversification of acupuncture and its clinical effects, brain effects of acupuncture and acupuncture clinical mechanisms. It is believed that the cooperation between countries and institutions should be strengthened in the future, and deeper research should be carried out on the research content that is both hot spot and frontier.
Subject(s)
Animals , Acupuncture , Acupuncture Therapy , Electroacupuncture , Moxibustion , Randomized Controlled Trials as Topic摘要
There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.
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Pulmonary arterial hypertension (PAH) is a devastating pulmonary circulation disease lacking high-efficiency therapeutics. The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata, a well-known traditional chinese medicine with cardiopulmonary protection capacity, on PAH by exploiting functional lipidomics. The rat model with PAH was successfully established for first, following Rhodiola crenulata water extract (RCE) treatment, then analysis of chemical constituents of RCE was performed, additional morphologic, hemodynamic, echocardiographic measurements were examined, further targeted lipidomics assay was performed to identify differential lipidomes, at last accordingly mechanism assay was done by combining qRT-PCR, Western blot and ELISA. Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls, mostly assigned to acylcarnitines, phosphatidylcholines, sphingomyelin associated with the PAH development. Excitingly, RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH. Furthermore, RCE was observed to reduce autophagy, confirmed by significantly inhibited PPARγ, LC3B, ATG7 and upregulated p62, and inactivated LKB1-AMPK signal pathway. Notably, we accurately identified the constituents in RCE, and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy. Altogether, RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH. This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.
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The relationship between adenosine receptor (AdoR) and myocardial ischemia (MI), effect of acupuncture for MI and action mechanism of acupuncture improving MI by regulating AdoR are summarized. The existing researches have preliminarily reflected that the improvement of MI treated with acupuncture may be achieved by influencing the expression of AdoR. However, there are still some limitations, e.g. most of the research regimens are single-acupoint, the research results are not entirely consistent and the interaction of AdoRs are ignored, all these need to be further verified and supplemented.
Subject(s)
Humans , Acupuncture , Acupuncture Points , Acupuncture Therapy , Myocardial Ischemia/therapy , Receptors, Purinergic P1摘要
Japanese encephalitis (JE) is a serious public health issue. This study was undertaken to better understand the relationship between JE distribution and environmental factors in China. JE data from 2005 to 2010 were retrieved from National Notifiable Disease Report System. ArcGIS, remote sensing techniques, and R software was used to exhibit and explore the relationship between JE distribution and environmental factors. Our results indicated that JE cases were mostly concentrated in warm-temperate, semitropical and tropical zones with annual precipitation > 400 mm; Broad-leaved evergreen forest, shrubs, paddy field, irrigated land, dryland, evergreen coniferous forest, and shrubland were risk factors for JE occurrence, and the former five were risk factors for counties with high JE incidence. These findings will inform the effective allocation of limited health resources such as intensive vaccination, surveillance and training in areas with high environmental risk factors.
Subject(s)
Humans , China , Epidemiology , Encephalitis, Japanese , Epidemiology , Virology , Environment , Epidemiological Monitoring , Incidence , Risk Factors摘要
A fluorescence enhancement probe (ZY8) for the detection of N2H4was designed and synthesized by employing 3-hydroxyflavone as a fluorophore,and its spectral properties had been investigated. The results showed that ZY8 had relatively good selectivity and specificity to N2H4in Tris-HCl-ethanol solution (9:1, V/V, pH 7.40). The fluorescent intensity of ZY8 exhibited good linear relationship with concentration of N2H4in the concentration range of 1.6×10-7mol/L-6.2×10-5mol/L,and its detection limit was estimated to be 1. 6×10-7mol/L. ZY8 itself had weak fluorescence, upon addition of N2H4, an approximate 9-fold fluorescence enhancement was observed, and the color of the solution changed from light grayish green to bright grass-green at UV light of 365 nm. So ZY8 might be used to the visual recognition of N2H4. ZY8 could detect N2H4in near-physiological pH range, and it had fast response and strong anti-interference ability. Moreover,ZY8 could be loaded as test paper for naked-eye detection of N2H4at mmol/L level in water solution,and it was also applied in the determination of N2H4in various water samples by the standard addition recovery experiments, with the recovery ratio ranged from 96.0% to 104.2% %, and RSD of all< 4%. The results of this study demonstrated that ZY8 had potential application to the detection of N2H4in the monitoring of environmental pollution.
摘要
<p><b>OBJECTIVE</b>This study aimed to explore the differences of membrane thickness and pressure on the paranasal sinus membrane in goats and analyze their causes. The results can provide theoretical basis and guidance for the issues of the maxillary sinus floor augmentation related to the membrane.</p><p><b>METHODS</b>The membrane was cut into two sizes from every sinus membrane. The membrane was fixed in formalin to obtain tissue specimens for the membrane thickness study and pressure study. The correlation between the two parameters was then analyzed, and appropriate statistical methods and software were selected.</p><p><b>RESULTS</b>The top of maxillary sinus, the bottom of maxillary sinus and the frontal sinus membrane thickness were (410.03 ± 65.97), (461.33 ± 91.37), (216.90 ± 46.47) µm. The pressure were (260.08 ± 80.12), (306.90 ± 94.37), (121.72 ± 31.72) kPa. The mean differences of the membrane thickness between the top of the maxillary sinus and the frontal sinus, bottom and frontal, and top and bottom were statistically significant (P < 0.05). The mean differences in membrane pressure were also statistically significant (P < 0.05).</p><p><b>CONCLUSION</b>The membrane thickness and pressure of the top and bottom of the maxillary sinus are higher than those of the frontal sinus membrane. However, the thickness and pressure of the bottom membrane are slightly higher than those of the top membrane. Pressure and membrane thickness are positively correlated in the sinus membrane.</p>
Subject(s)
Animals , Goats , Maxillary Sinus , Sinus Floor Augmentation , Software摘要
Glioblastoma(GBM)is one of the most common primary intracranial tumor that has high de-gree of malignancy ,invasive ability and a fatal prognosis .In recent years ,with the development of modern technol-ogy in biomedical sciences ,the understanding on GBM has developed gradually from pathological diagnosis to mo -lecular classifications ,which is based on the molecular characteristics of genetic signatures .Based on gene expres-sion and DNA methylation patterns , primary glioblastoma is divided into four subtypes , including the classical , neural,proneural and mesenchymal .These molecular classifications are closely relevant to the biological charac-teristics of glioblastoma .This review briefly introduces the molecular classifications of primary glioblastoma , but mainly focuses on the changes of the major genetic EGFR ,PTEN and PI3K,CDKN2A in the classical subtype of GBM,and discusses the treatment strategies for primary glioblastoma .
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AIDS has become a global disease,and a variety of drugs are used in the treatment of AIDS ,but the interindividual variabilities in efficacy and toxicity remain important limitations for the use of these drugs.Studies have shown genetic polymor-phism is the main reason for interindividual variabilities of drug reaction.In recent years,scholars focused on the pharmacog-enomics of anti-AIDS drugs and found that genetic polymor-phisms,in large part,determine the interindividual variabilities of the responese of these drugs.This paper reviews the research progress on pharmacogenomics of the four types of anti-AIDS drugs commonly used in China,including nucleoside reverse transcriptase inhibitors (NRTIs),non-nucleoside reverse tran-scriptase inhibitors (NNRTIs),protease inhibitors (PIs)and integrase inhibitors (raltegravir).
摘要
ObjectiveTo investigate the impacts of neural stem cells (NSCs) transplantation on spinal pathology and ultrastructure after spinal cord injury (SCI) in rats and probe into the protective role of tacrolimus (FK506) on neural regeneration.MethodsCompressive SCI at T8 was induced in the adult SD rats,which were randomly assigned to the control group,FK506 group,NSCs group and NSCs + FK506 group.The differences of neural regeneration in each group were compared at days 7,14,28 and 56 after injury by motor evoked potentials ( MEP),HE staining,immunohistochemical staining,ultrastructure observation and image analysis of the myelinated fiber. ResultsThe MEP latency in the NSCs + FK506 group was significantly shorter than that in other groups at day 28 ( P < 0.05 ).HE staining revealed that only local necrosis presented in the NSCs + FK506 group at day 56.More BrdU and NF-200 positive cells were detected with immunohistochemical staining in the other three groups as compared with the control group.Moreover,the positive cells in the NSCs + FK506 group also outnumbered the FK506 group and NSCs group.Electron microscope scan showed edema under the membrane of large myelin sheath in the control group,and classic new myelin sheath and neuraxis in the NSCs + FK506 group at day 56.The regeneration of the nerve fiber in the NSCs + FK506 group was better than that of other three groups (P <0.01 ).ConclusionAfter NSCs transplantation for SCI rats,the early combination use of FK506 can improve the pathology and ultrastructure of the regenerative nerve fiber and is conducive to nerve regeneration.
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To investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody Fab' fragment and lidamycin (LDM) prepared with different linkers. The immunoconjugates were prepared by linking Fab' to lysine-69 of LDM apoprotein by SPDP, LCSPDP, SMBS or SSMPB as the intermediate drug linkers. Immunoreactivities of the conjugates were determined by ELISA. The cytotoxicities of the conjugates were examined by clonogenic assay. In vivo antitumor effects of the conjugates were evaluated in nude mice bearing subcutaneously implanted HT-1080 tumor. ELISA assay showed that the conjugates retained part of the immunoreactivity of 3G11 against the antigen. The cytotoxicities of the Fab'-SMBS-LDM and Fab'-SSMPB-LDM to HT-1080 cells were significantly potent, compared with Fab'-SPDP-LDM, Fab'-LCSPDP-LDM and free LDM. In animal models at the same condition, free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM inhibited the growth of HT-1080 tumor by 70.9%, 74.8% and 72.3%, while Fab'-SMBS-LDM and Fab'-SSMPB-LDM reached 78.0% and 87.7%, respectively. The median survival time of the mice treated with free LDM, Fab'-SPDP-LDM and Fab'-LCSPDP-LDM were prolonged by 71.9%, 82.2% and 107.5%, respectively, compared with that of untreated group. Whereas, the median survival time of Fab'-SMBS-LDM and Fab'-SSMPB-LDM were prolonged by 145.2% and 165.8%, respectively, indicating that Fab'-SSMPB-LDM was more effective than Fab'-SMBS-LDM in tumor suppression and life span prolongation. Fab'-SSMPB-LDM has more marked selective antitumor efficacy and lower toxicity, and might be a novel candidate for cancer therapy.
Subject(s)
Animals , Humans , Mice , Aminoglycosides , Pharmacology , Antibiotics, Antineoplastic , Pharmacology , Antibodies, Monoclonal , Allergy and Immunology , Cell Line, Tumor , Cell Proliferation , Collagenases , Allergy and Immunology , Enediynes , Pharmacology , Fibrosarcoma , Pathology , Immunoconjugates , Pharmacology , Immunoglobulin Fab Fragments , Allergy and Immunology , Matrix Metalloproteinase Inhibitors , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Tumor Burden摘要
Objective To observe the levels of alanine aminotransferase(ALT), total bilirubin(TBIL), hyaluronic acid (HA), procollagen type Ⅲ aminoterminal peptide (P Ⅲ NP) and larninin (LN) in the sera of rats infected with Clonorchis sinensis (C. sinensis) after treatment of albendazole combined with milkvetch root. Methods Thirty-two healthy adult Wistar rats were randomly divided into four groups with 8 in each based on body mass: control group, non-treatment group, Albendazole group(ALB group) and albendazole combined with milkvetch root group(ALB+MR group). The rats in non-treatmen, ALB and ALB+MR groups were infected orally with metacercariae of C. sinensis 50 per rat. The rats in control group were mock-infected with saline. The rats in ALB group were treated to each rat with 50 mg/kg alhendazole for 5 days, and ALB+MR groups were given to same treat with albendazole, meanwhile each rat injected with 800 mg/kg milkvetch root intraperitoneally for 30 days. All rats were killed after infestation 14 weeks and their sera samples were collected to detect ALT, TBIL, HA, PⅢNP, LN. Results There were statistically significant differences in the levels of ALT and LN in the sera of rats between groups(F=31.40,11.82, P<0.01). Compared with control[ (47.88±4.88)U/L, (51.20±4.12)μg/L], the levels of ALT and LN in rats in non-treatment group [(85.50±9.65)U/L, (64.20±4.18) μg/L] and ALB group [(65.29± 7.78) U/L, (58.23±2.55) μg/L] were significantly increased (P<0.05). Compared with non-treatment group, the levels of ALT and LN in rats in ALB group and ALB+MR groups[(50.25±9.29)U/L, (53.68±5.63)μg/L] were significantly decreased(P<0.05), and they decreased more obviously in ALB+MR group (P<0.05). There were statistically significant differences in the levels of TBIL, PⅢNP and HA in the sera of rats between groups (χ2=15.309,21.418,19.759, P<0.01). Compared with control[(0.700±0.350)μmol/L, (26.085±4.075)μg/L, (81.935±42.550)μg/L], the levels of TBIL, PⅢNP and HA in rats in non-treatment group(2.400 μmol/L, 46.220 μg/L,310.885 μg/L) and ALT group(1.200 μmol/L,36.540 μg/L, 178.010 μg/L) were significantly increased(P<0.05). Compared with non-treatment group, the level of TBIL in ALT+MR group(0.750 μmol/L), the levels of pⅢNP and HA in ALT and ALT+MR group(30.470,100.240 μg/L) were significantly decreased(P< 0.05). The levels of TBIL, PⅢNP and HA decreased more obviously in ALB+MR group(P<0.05). Conclusions The liver function in rats infected with C. sinensis is abnormal. The liver function and fibrosis are improved after treatment with albendazole or albendazole combined with milkvetch root. The treatment of albendazole combined with milkvetch root is more effective.
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<p><b>BACKGROUND</b>Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination of bevacizumab and chemotherapy in a series of six patients with recurrent malignant glioma and investigated the molecular alterations in cancer pathways using the surgical biopsies from these patients.</p><p><b>METHODS</b>Standard therapy with primary resection followed by adjuvant chemoradiotherapy had failed in all patients. Bevacizumab was administered at a dose of 10 mg/kg every 2 weeks. Concomitantly, four patients received temozolomide (50 mgxm(-2)xd(-1)), one patient irinotecan (125 mg/m(2) every 2 weeks) and one patient topotecan (1.2 mgxm(-2)xd(-1)). Response to therapy was mainly determined by magnetic resonance imaging. The expression of Ras, phosphorylated mitogen activated protein kinase (p-MAPK), phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were semiquantitatively assessed by immunohistochemistry using surgical biopsies before the initial treatment.</p><p><b>RESULTS</b>Five of the six patients had a radiographic response. Three were complete response, and two were partial response. Only one patient had progressive disease. The 6-month progession-free survival (PFS) was 33% and the median PFS was 15 weeks, with a range of 6 to more than 60 weeks. Of the three core pathways analyzed in this study, the Ras/MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathways were more likely to be associated with the treatment response to bevacizumab. In two younger patients (ages < 50) with complete response, simultaneous overexpression of p-MAPK, p-AKT and p-mTOR might be the crucial feature.</p><p><b>CONCLUSIONS</b>Bevacizumab in combination with chemotherapeutic agents may be an effective strategy for patients with recurrent malignant glioma. Activated MAPK and AKT might be possible biomarkers for selecting suitable patients for this targeted therapy.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Angiogenesis Inhibitors , Therapeutic Uses , Antibodies, Monoclonal , Therapeutic Uses , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Phytogenic , Pharmacology , Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Camptothecin , Therapeutic Uses , Disease-Free Survival , Glioma , Drug Therapy , Metabolism , Mortality , Pathology , Immunohistochemistry , Magnetic Resonance Imaging摘要
<p><b>BACKGROUND</b>Glioblastoma multiforme (GBM) is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM.</p><p><b>METHODS</b>A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients' progression free survival (PFS) time and overall survival (OS) time.</p><p><b>RESULTS</b>Age, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors (P < 0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age <or= 50 years, preoperative KPS score >or= 80, KPS score change after operation >or= 0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors (P < 0.05) for patients' clinical outcomes.</p><p><b>CONCLUSIONS</b>Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Glioblastoma , Pathology , Radiotherapy , General Surgery , Kaplan-Meier Estimate , Multivariate Analysis , Prognosis , Retrospective Studies摘要
<p><b>OBJECTIVE</b>To develop the modified P-POSSUM equation and the modified Cr-POSSUM equation and compare their performances with POSSUM in forecasting in-hospital morbidity and mortality of colorectal cancer.</p><p><b>METHODS</b>Data of 903 patients undergone operation of colon and rectal cancers from 1992 to 2005 in our department were enrolled in this study. ROC curve was applied to judge the differentiation ability of each score. Model goodness-or-fit was tested by the Hosmer-Lemeshow statistic and subgroup analysis was performed by the ratio of observed to expected deaths (O:E ratio). A 70:30 percent split-sample validation technique was adopted for model development and testing. Stepwise logistic regression was used to develop the modified P-POSSUM and the modified Cr-POSSUM. Their performance in validating sample, colonic cancer sample, rectal cancer sample, elective surgery sample, emergency surgery sample, curative surgery sample and palliative surgery sample was tested by ROC curve, Hosmer-Lemeshow statistic and O:E ratio.</p><p><b>RESULTS</b>The modified P-POSSUM showed good discrimination in all samples except the emergency surgery and palliative surgery. The predicted mortality of modified P-POSSUM was very close to the observed mortality. However, the modified Cr-POSSUM showed good discrimination in all samples except the palliative surgery. The predicted mortality was higher than the observed mortality, but still within the 95% confidence interval (CI) of the observed mortality. Both the modified models offered better accuracy than the P-POSSUM.</p><p><b>CONCLUSION</b>The modified P-POSSUM and the modified Cr-POSSUM model provide an accurate prediction of inpatient mortality in Chinese colorectal cancer patients.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Colorectal Neoplasms , Mortality , Hospital Mortality , Logistic Models , Outcome Assessment, Health Care , Methods , ROC Curve摘要
Background and purpose:Hepatocellular carcinoma(HCC) is one of the most common malignancies in the world,It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection is considered the best curative option,the 5-year survival rate could reach 50%,especially in the patients with lesions less than 5 cm in diameter and good residual liver function.However curative surgery is feasible for only about 20% of patients.Transcatheter arterial chemoembolization(TACE) has been demonstrated that its short-term curative effect is better than the other nonsurgical treatments.However,it has not provided any survival benefit.Many studies have been done to improve the overall therapeutic effects of HCC with multi-modality approaches.The purpose of our trial was to evaluate the effects of TACE combined with 3-dimensional conformal radiation therapy(3-DCRT) for primary hepatic carcinoma.Methods:90 patients with primary hepatic carcinoma were randomly divided into two groups :45 were treated with 3-DCRT plus TACE and the others were treated with TACE alone.For TACE,80-120 mg cisplatin and 1 000 mg 5-Fluorouracil or 30 mg hydroxycamptothecine)were perfused into the hepatic arteries,then 50-100 mg adriamycin(or epirubicin) or 16 mg mitomycin C and iodized oil 10-30 ml were given to embolize the hepatic arteries,and followed by 1-2 mm gel form particles.TACE of 1-3 sessions was given to both groups.For the combined group,3-DCRT was given by 6MV X-ray.The patients with planned target volume(PTV) lesser than 512 cm~(3) received a total dose of 45-56 Gy,4.5-7 Gy per fraction,and the patients with PTV larger than 512 cm~(3) received a total dose of 45-56 Gy,2.5-4.5 Gy per fraction,5 times every week.Results:The response rates (CR+PR)of 3-DCRT plus TACE group and TACE alone group were 91.1% and 60%,respectively(?~(2)=11.79,P