A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these...A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.展开更多
Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint i...Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint injections, concentration of 0.1 mg/0.l ml MMC every point, 1 cm interval of injection. After the injections, the tumor size of mice reduced and at last disappeared (ratio of inhibited tumor 59.32% in 0.05 mg MMC group, 43.86% in 0.1 mg MMC group).The pathologic examination showed coagulatic necrosis of the tumor tissues. The higher concentration of antineoplastic agent (0.2 mg MMC) could make the tumors enlarged (ratio of inhibited tumor -15.3%). The tissues and vessels around the tumors were not injured, if MMC overflow out off the tumor.展开更多
The recent spring up of the antineoplastic agents and the prolonged survival bring both challenge and chance to radiological practice.Radiological methods including CT,MRI and PET play an increasingly important role i...The recent spring up of the antineoplastic agents and the prolonged survival bring both challenge and chance to radiological practice.Radiological methods including CT,MRI and PET play an increasingly important role in evaluating the efficacy of these antineoplastic drugs.However,different antineoplastic agents potentially induce different radiological signs,making it a challenge for radiological response evaluation,which depends mainly on one-sided morphological response evaluation criteria in solid tumors(RECIST)in the status quo of clinical practice.This brings opportunities for the development of radiomics,which is promising to serve as a surrogate for response evaluations of anti-tumor treatments.In this article,we introduce the basic concepts of radiomics,review the state-of-art radiomics researches with highlights of radiomics application in predictions of molecular biomarkers,treatment response,and prognosis.We also provide in-depth analyses on major obstacles and future direction of this new technique in clinical investigations on new antineoplastic agents.展开更多
Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartor...Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.展开更多
AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the ...AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P 【 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.展开更多
INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo ...INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.展开更多
Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characteri...Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.展开更多
INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal ...INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.展开更多
AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibr...AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.展开更多
AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the im...AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.展开更多
PURPOSE: To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture therapy was simultaneously applied during chemotherapy, T ce...PURPOSE: To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture therapy was simultaneously applied during chemotherapy, T cells and activity of NK cell of patients were determined before electroacupuncture treatment (before chemotherapy) and after 4-course electro-acupuncture treatments. RESULTS: Before chemotherapy, CD3 was low within the normal range, CD4 was much lower than the normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal range. After one month of chemotherapy combined with electro-acupuncture, no decline of all the indices was found (P > 0.05). CONCLUSION: Electro-acupuncture can really increase the immune function of patients of chemotherapy.展开更多
AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines ...AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.展开更多
To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentra...To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca ++ Mg ++ ATPase).展开更多
Ovarian tumor may occur in women ofany age, but mostly seen in women duringtheir child-bearing period. The disease shouldbe treated mainly by surgical operation,supplemented by radiotherapy and chemo-therapy. However,...Ovarian tumor may occur in women ofany age, but mostly seen in women duringtheir child-bearing period. The disease shouldbe treated mainly by surgical operation,supplemented by radiotherapy and chemo-therapy. However, the above therapies maycause a series of toxic side-effects, such asalopecia, diarrhea, edema, anorexia, nausea,dry mouth, spontaneous perspiration, headache,展开更多
Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into pla...Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into play.1 At present, there are two main subjects for the researches, that is, blocking the precancerous lesions and blocking the develop-ment of tumors. The former focuses on the removing of carcinogenic factors and on the chemoprophylaxis of cancer, while the latter on the inhibition of cancer cell infiltration and cancerometastasis. These are summarized as follows.展开更多
AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive e...AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive effect of IFN plusribavirin treatment are lacking.METHODS:A total of 101 patients(62 males and 39 females,mean age 55.1±1.4 years)with histologically proven HCVrelated liver cirrhosis plus compatible biochemistry andultrasonography were enrolled in the study.Biochemistryand ultrasonography were performed every 6 mo.Ultrasoundguided liver biopsy was performed on all detected focallesions.Follow-up lasted for 5 years.Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytesnuclei,was expressed as AgNOR-Proliferative index(AgNOR-PI)(cut-off=2.5).Forty-one patients(27 males,14 females)were only followed up after the end of anyearly treatment with IFN-alpha2b(old treatment controlgroup=OTCG).Sixty naive patients were stratified accordingto sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b+ribavirin(treatmentgroup=TG),the remaining were not treated(control group=CG).Nonresponders(NR)or relapsers in the TG receivedfurther IFN/ribavirin treatments after a 6 mo of withdrawal.RESULTS:AgNOR-PI was significantly lowered by IFN(P<0.001).HCC incidence was higher in patients withAgNOR-PI>2.5(26% vs3%,P<0.01).Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCCduring follow-up.The Kaplan-Mayer survival curves showedstatistically significant differences both between OTCG andCG(P<0.004)and between TG and CG(P<0.003).CONCLUSION:IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best resultsin terms of HCC prevention.AgNOR-PI is a useful markerof possible HCC development.展开更多
目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,...目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。展开更多
文摘A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.
文摘Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint injections, concentration of 0.1 mg/0.l ml MMC every point, 1 cm interval of injection. After the injections, the tumor size of mice reduced and at last disappeared (ratio of inhibited tumor 59.32% in 0.05 mg MMC group, 43.86% in 0.1 mg MMC group).The pathologic examination showed coagulatic necrosis of the tumor tissues. The higher concentration of antineoplastic agent (0.2 mg MMC) could make the tumors enlarged (ratio of inhibited tumor -15.3%). The tissues and vessels around the tumors were not injured, if MMC overflow out off the tumor.
文摘The recent spring up of the antineoplastic agents and the prolonged survival bring both challenge and chance to radiological practice.Radiological methods including CT,MRI and PET play an increasingly important role in evaluating the efficacy of these antineoplastic drugs.However,different antineoplastic agents potentially induce different radiological signs,making it a challenge for radiological response evaluation,which depends mainly on one-sided morphological response evaluation criteria in solid tumors(RECIST)in the status quo of clinical practice.This brings opportunities for the development of radiomics,which is promising to serve as a surrogate for response evaluations of anti-tumor treatments.In this article,we introduce the basic concepts of radiomics,review the state-of-art radiomics researches with highlights of radiomics application in predictions of molecular biomarkers,treatment response,and prognosis.We also provide in-depth analyses on major obstacles and future direction of this new technique in clinical investigations on new antineoplastic agents.
基金supported by project MARBIOTECH,grant NORTE-07-0124-FEDER-000047-BPD-2013-06partially funded by project MARBIOTECH(reference NORTE-070124-FEDER-000047)+6 种基金co-financed by the North Portugal Regional Operational Programme(ON.2-O Novo Norte)the National Strategic Reference Framework(NSRF)the European Regional Development Fund(ERDF)the ERDF,through the Competitiveness and TradeExpansion Program(COMPETE)national funds provided by the Foundation for Science and Technology(FCT)project PEst-C/MARL-1A0015/2013the financial aid provided by the Master of Marine Sciences-Marine Recourses,of the Institute of Biomedical Sciences Abel Salazar,University of Porto
文摘Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.
基金Surported by the Funds of Hundred Outsdanding Persons project of Shanghai(97BR029)Science and Technology Commission of Shanghai(984419067)
文摘AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P 【 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.
基金Supported by the Youth Science Grant of Jiangshu Province,No.BQ98048.
文摘INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.
文摘Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.
基金Supported by the Hebei Provincial Scientific Commission, No. 97276162D
文摘INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.
文摘AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.
基金Supported by a faculty research grant of Yonsei University College of Medicine for 2002,No.2002-06
文摘AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.
文摘PURPOSE: To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture therapy was simultaneously applied during chemotherapy, T cells and activity of NK cell of patients were determined before electroacupuncture treatment (before chemotherapy) and after 4-course electro-acupuncture treatments. RESULTS: Before chemotherapy, CD3 was low within the normal range, CD4 was much lower than the normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal range. After one month of chemotherapy combined with electro-acupuncture, no decline of all the indices was found (P > 0.05). CONCLUSION: Electro-acupuncture can really increase the immune function of patients of chemotherapy.
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.
文摘To clarify the possible mechanisms of α anordin and probimane on calmodulin Ca ++ Mg ++ APTase system, enzyme dynamic study was carried out by determining three dynamic parameters [the substrate concentration(ATP) response curve, dose(inhibitors) response curve and time response curve]. Our data have shown that the inhibitory rates of α anordrin and probimane are unrelated to substrate(APT) concentrations, but related to calmodulin concentrations. The inhibition of α anordrin and probimane is very quick that is completed within 1 to 5 min and can maintain more than 1 hr in the same inhibitory rates. So it is possible that α anordrin and probimane are calmodulin competitors with calmodulin like binding whose actions can occur by affecting the reaction balance of substrate and product on target enzymes of calmodulin( Ca ++ Mg ++ ATPase).
文摘Ovarian tumor may occur in women ofany age, but mostly seen in women duringtheir child-bearing period. The disease shouldbe treated mainly by surgical operation,supplemented by radiotherapy and chemo-therapy. However, the above therapies maycause a series of toxic side-effects, such asalopecia, diarrhea, edema, anorexia, nausea,dry mouth, spontaneous perspiration, headache,
文摘Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into play.1 At present, there are two main subjects for the researches, that is, blocking the precancerous lesions and blocking the develop-ment of tumors. The former focuses on the removing of carcinogenic factors and on the chemoprophylaxis of cancer, while the latter on the inhibition of cancer cell infiltration and cancerometastasis. These are summarized as follows.
文摘AIM:To determine the role of interferon(IFN)with or withoutribavirin in preventing or delaying hepatocellular carcinoma(HCC)development in patients with hepatitis C virus(HCV)related cirrhosis.Data on the preventive effect of IFN plusribavirin treatment are lacking.METHODS:A total of 101 patients(62 males and 39 females,mean age 55.1±1.4 years)with histologically proven HCVrelated liver cirrhosis plus compatible biochemistry andultrasonography were enrolled in the study.Biochemistryand ultrasonography were performed every 6 mo.Ultrasoundguided liver biopsy was performed on all detected focallesions.Follow-up lasted for 5 years.Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytesnuclei,was expressed as AgNOR-Proliferative index(AgNOR-PI)(cut-off=2.5).Forty-one patients(27 males,14 females)were only followed up after the end of anyearly treatment with IFN-alpha2b(old treatment controlgroup=OTCG).Sixty naive patients were stratified accordingto sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b+ribavirin(treatmentgroup=TG),the remaining were not treated(control group=CG).Nonresponders(NR)or relapsers in the TG receivedfurther IFN/ribavirin treatments after a 6 mo of withdrawal.RESULTS:AgNOR-PI was significantly lowered by IFN(P<0.001).HCC incidence was higher in patients withAgNOR-PI>2.5(26% vs3%,P<0.01).Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCCduring follow-up.The Kaplan-Mayer survival curves showedstatistically significant differences both between OTCG andCG(P<0.004)and between TG and CG(P<0.003).CONCLUSION:IFN/ribavirin treatment associated with re-treatment courses of NR seems to produce the best resultsin terms of HCC prevention.AgNOR-PI is a useful markerof possible HCC development.
文摘目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。