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Sample records for adriamycin

  1. Hepatopathy following irradiation and adriamycin

    International Nuclear Information System (INIS)

    This report describes two cases of hepatopathy following irradiation and adriamycin at doses and volumes of irradiation ordinarily considered within the tolerance of hepatic function. In one case, fatal hepatopathy followed 2400 rad/17 fractions/28 days to the entire liver with preceding and concurrent adriamycin. In the second case moderate clinical changes occurred after treatment in which much of the right lobe of the liver was shielded following 2500 rad/23 fractions/32 days with adriamycin administered before, during, and after irradiation. The locally enhancing effects of adriamycin on hepatic tolerance to irradiation are discussed

  2. Adriamycin--irradiation cutaneous complications

    International Nuclear Information System (INIS)

    Four cases of abnormally severe skin reactions including an instance of skin necrosis occurred in patients with breast cancer who were treated with cyclophosphamide, adriamycin and irradiation concurrently following mastectomy. These unusual skin reactions apparently resulted from the interaction of radiation with adriamycin and prompted us to modify both the radiation dose and the timing of administration of chemotherapy. To date, no unusual or severe skin reactions have been observed in 14 patients who have received chemotherapy with adriamycin plus radiation in accord with this modified treatment plan

  3. Adriamycin-induced fetal hydronephrosis

    OpenAIRE

    Anderson Gonçalves; Willy G. França; Suzana G. Moraes; Luis A.V. Pereira; Lourenço Sbragia

    2004-01-01

    INTRODUCTION: At the end of pregnancy, the amniotic fluid (AF) depends basically on renal function, corresponding to fetal urine. Changes in AF, especially oligohydramnios, are reported in association with fetal hydronephrosis (FH). The experimental model using adriamycin in pregnant female rats has a teratogenic effect and has been classically employed to study esophageal atresia. Nevertheless, adriamycin promotes FH with high frequency as well. In the present study, using this animal model,...

  4. Adriamycin-induced fetal hydronephrosis

    Directory of Open Access Journals (Sweden)

    Anderson Gonçalves

    2004-12-01

    Full Text Available INTRODUCTION: At the end of pregnancy, the amniotic fluid (AF depends basically on renal function, corresponding to fetal urine. Changes in AF, especially oligohydramnios, are reported in association with fetal hydronephrosis (FH. The experimental model using adriamycin in pregnant female rats has a teratogenic effect and has been classically employed to study esophageal atresia. Nevertheless, adriamycin promotes FH with high frequency as well. In the present study, using this animal model, we tried to identify the incidence and microscopic changes of FH, as well as its correlation with AF weight. MATERIALS AND METHODS: Eight Spreague-Dawley pregnant female rats received adriamycin 2.2 mg/kg on the 8th and 9th gestational days (considering term gestation = 22 days. Those fetuses that received adriamycin (Adriamycin Group were compared with fetuses from 2 female rats (Control Group, which received 0.9% saline solution. On the 21.5 gestational day, the fetuses were collected by cesarean incision, sacrificed, and examined for macro and microscopic changes in kidneys and ureters. Fetuses with bilateral hydronephrosis formed the Hydronephrosis Group. AF weight was determined as well. RESULTS: Hydronephrosis occurred in 70 (95% of the 74 fetuses in the adriamycin group against none of the 21 fetuses from the control group. The amniotic fluid weight was increased in the adriamycin group in relation to the control group (p < 0.001. The histomorphometric study revealed dilation of the renal pelvis and reduction of renal parenchyma in the hydronephrosis group in relation to the control group. Severe cortical atrophy, cortical tubular atrophy and medullar atrophy were observed in the hydronephrosis group. CONCLUSIONS: Slight renal lesions were in agreement with changes in AF weight, since they suggest that there was production of urine with the maintenance of AF.

  5. Toxicity of Magnetic Albumin Microspheres Bearing Adriamycin

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Magnetic albumin microspheres bearing adriamycin (ADM-MAM) is a novel chemotherapeutic compound with site-specific drug delivery characteristics. The acute and subacute toxic tests of the compound, local irritating test and anaphylactic test were performed on mice and guinea pigs. The results showed there was no macroscopically and microscopically direct cytotoxic injuries of the compound to the animal organs or to the cells. The LD50 value of the compound was higher than that of the single used adriamycin, indicating that the compound was less toxic than the single adriamycin and quite safe in its therapeutic dosage. Furthermore, there was also no side effects or toxic reactions to be observed on clinical patients with advanced carcinoma or gastric cancer.

  6. Adriamycin induces H2AX phosphorylation in human spermatozoa

    Institute of Scientific and Technical Information of China (English)

    Zhong-Xiang Li; Ting-Ting Wang; Yan-Ting Wu; Chen-Ming Xu; Min-Yue Dong; Jian-Zhong Sheng; He-Feng Huang

    2008-01-01

    Aim: To investigate whether adriamycin induces DNA damage and the formation of γH2AX (the phosphorylated form of histone H2AX) foci in mature spermatozoa. Methods: Human spermatozoa were treated with adriamycin at different concentrations. γH2AX was analyzed by immunofluorescent staining and flow cytometry and double- strand breaks (DSB) were detected by the comet assay. Results: The neutral comet assay revealed that the treatment with adriamycin at 2 μg/mL for different times (0.5, 2, 8 and 24 h), or for 8 h at different concentrations (0.4, 2 and 10 μg/mL), induced significant DSB in spermatozoa. Immunofluorent staining and flow cytometry showed that the expression of γH2AX was increased in a dose-dependent and time-dependant manner after the treatment of adriamycin. Adriamycin also induced the concurrent appearance of DNA maintenance/repair proteins RAD50 and 53BP1 with γH2AX in spermatozoa. Wortmannin, an inhibitor of the phosphatidylinositol 3-kinase (PI3K) family, abolished the co-appearance of these two proteins with γH2AX. Conclusion: Human mature spermatozoa have the same response to DSB-induced H2AX phosphorylation and subsequent recruitment of DNA maintenance/repair proteins as somatic cells.

  7. Effects of adriamycin and x irradiation on the murine duodenum

    International Nuclear Information System (INIS)

    The effects of a single dose of irradiation at various times following a single dose of Adriamycin have been evaluated at the cellular level (duodenal crypt cell survival) and whole-animal level (LD/sub 50/6/; the dose required to kill 50% of the animals in 6 days). Qualitatively, the 10-clone doses (the x-ray dose required to reduce crypt survival to 10) parallel the data for the effects of Adriamycin on the rate of DNA synthesis. In contrast, changes in the slopes s(D0) of the survival curves for the combined treatments do not correlate with the ADR-induced inhibition of DNA synthesis. The LD/sub 50/6/ doses for the combined treatments also parallel the cellular toxicity data initially but for intervals from 2 to 14 days, when the cellular parameters are back to normal, there is still evidence for an Adriamycin-enhanced radiotoxicity. The discrepancy between the Adriamycin-enhanced duodenal cellular radiotoxicity and whole-body radiotoxicity is not surprising with a systemic drug like Adriamycin; however, neither the specific tissue(s) affected nor the specific underlying molecular and cellular mechanism(s) are evident in the studies to date

  8. Lisinopril Protects Against the Adriamycin Nephropathy and Reverses the Renalase Reduction: Potential Role of Renalase in Adriamycin Nephropathy

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    Pengxun Han

    2013-09-01

    Full Text Available Aims: To investigate the potential role of renalase in adriamycin nephropathy and the effect of lisinopril on the regulation of renalase. Methods: Adriamycin nephropathy was induced in male Wistar rats (n=12 by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model group or a treatment group, to which were administered distilled water or the angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks. Six normal rats served as controls. At the end of study, physiological parameters and systolic blood pressure were measured. Glomerulosclerosis and tubulointerstitial injury were assessed by histopathology Renalase protein expression in kidney was quantified by immunohistochemistry and immunoblotting. The serum concentration and urinary excretion of renalase were determined by enzyme-linked immunosorbent assay. Results: In model group rats, proteinuria and systolic blood pressure were elevated. Increased serum renalase concentration was observed; however, renalase protein expression in the kidney was significantly decreased. Compared with the model group, decreased proteinuria, lower systolic blood pressure, and fewer morphologic lesions were detected in the treatment group. Although levels of serum renalase were similar, accumulation of renalase in urine and kidney tissue increased notably in the treatment group compared with the model group. Conclusions: This study suggests that renalase may be involved in the process of adriamycin-induced renal injuries. Lisinopril may attenuate adriamycin-induced kidney injury by controlling blood pressure, which may be partially attributed to the renalase expression and secretion.

  9. Effect of hepatic irradiation on the toxicity and pharmacokinetics of adriamycin in children

    International Nuclear Information System (INIS)

    The effect of hepatic irradiation on adriamycin toxicity and pharmacokinetics was studied in 10 children who received adriamycin with concurrent abdominal irradiation for Wilms' tumor. Hepatic irradiation to 2400 to 2700 rad at 100 to 150 rad per fraction did not alter the clinical toxicity or plasma pharmacokinetics of adriamycin

  10. Normalizing renal reducing ability prevents adriamycin-induced proteinuria

    International Nuclear Information System (INIS)

    Reactive oxygen species play an important role in adriamycin (ADR) nephropathy. We showed by in vivo electron paramagnetic resonance (EPR) that renal reducing ability (RRA) declined on the 7th day after ADR administration. Proteinuria appeared after the decline in RRA. The aim of this study was to prove by in vivo EPR whether the decline in RRA is altered by scavengers such as dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU) and that it is this change which is responsible for the proteinuria in ADR nephropathy. By showing that DMSO and DMTU ameliorate the RRA, we demonstrate that the decline in RRA is related to ADR-induced proteinuria

  11. CdS Quantum Dots as Fluorescence Probes for Detection of Adriamycin Hydrochloride

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Water-soluble CdS quantum dots (CdS-QDs) capped with thioglycolic acid were easily prepared, and a detection method of adriamycin was presented based on the fluorescence quenching of CdS-QDs. It was found that a complex could be formed between cetyltrimethyl ammonium bromide(CTAB) and CdS-QDs by using electrostatic interaction in Britton-Robinson(BR) buffer at pH = 7. 00, and the strong fluorescence emission of the complex was observed at 500nm when the complex was excited at 378 nm. The presence of adriamycin, however, could strongly quench the fluorescence through hydrophobic interaction. The overall quenching percentage as a function of adriamycin concentration matches the Stern-Volmer equation very well. These properties make CdS-QDs a potential fluorescence probe for the detection of adriamycin. The detection limit(3σ) of adriamycin is approximately 10-9 mol/L.

  12. A limited sampling procedure for estimating adriamycin pharmacokinetics in cancer patients.

    OpenAIRE

    Launay, M. C.; Milano, G.; Iliadis, A.; Frenay, M.; Namer, N.

    1989-01-01

    The aim of this study was to find a procedure allowing estimation of individual pharmacokinetic parameters for adriamycin with minimal cost and disturbance for the patient. Twenty-five patients with breast cancer were treated by short infusion of adriamycin at a dose of 12 mg m-2 week-1 (41 courses). Population characteristics were determined on 15 randomly chosen courses (10 patients, group I) in order to define two optimal sampling times (26 min and 24 h) and to perform Bayesian estimation ...

  13. Adriamycin increases podocyte permeability: evidence and molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    李晓忠; 袁海涛; 张学光

    2003-01-01

    Objective To investigate the increased podocyte permeability by evidence of adriamycin (AD) and its molecular mechanism.Methods In this study, we explored the direct effects of AD on cultured mouse podocytes and the potential protection effects of Dexamethasome (Dex).Results After 24-hour AD (5×10-7 mol/L) treatment, albumin passage through podocyte monolayers was increased by 2.27-fold (P<0.01). AD caused a 62% decrease in Zonula Occluden -1 (ZO-1) protein (P<0.05), suggesting that AD might increase podocyte permeability by disrupting tight junctions. Dex (1×10-6 mol/L), co-administered with AD, protected podocytes from AD-induced increased albumin passage. This may be linked with an increased P-cadherin protein level to 1.93 fold of control (P<0.01).Conclusions AD has a direct, detrimental effect on podocyte permeability, probably through disrupting tight junctions; Dex could protect against AD-induced high podocyte permeability by upregulating adherent protein P-cadherin.

  14. Co-induction of glucose regulated proteins and adriamycin resistance in Chinese hamster cells

    International Nuclear Information System (INIS)

    Glucose deprivation, anoxia, calcium ionophore A23187 or 2-deoxyglucose all inducers of glucose regulated proteins (grps), also lead to a significant induction of resistance to the drug adriamycin. In the case of anoxia, A23187 and 2-deoxyglucose, the induction of resistance correlates with both the application of the inducing stress and the induction of grps. In the case of glucose deprivation, the onset of resistance correlates with the onset of glucose deprivation and precedes grp induction. Removal of each grp including condition results in the rapid disappearance of this resistance in a manner which correlates with the repression of the grps. This drug resistance can be induced in confluent cells or in actively proliferating cells, although the effect is greater in the more sensitive proliferating cells. Induction of heat shock proteins (hsps) does not appear to lead to any major change in adriamycin resistance. Grp induced cells retain less adriamycin than do controls with the greatest reduction occurring during anoxia, which is also the strongest inducer of grps and resistance. The authors propose that the application of a grp inducing stress leads to a concurrent induction in drug resistance, possibly via the translocation of grps in the cell. Finally, they also observed that adriamycin itself can induce both hsps and grps. It is possible that adriamycin exposure may correspondingly induce auto-resistance

  15. NMR spectroscopy analysis of phosphorus metabolites and the effect of adriamycin on these metabolite levels in an adriamycin-sensitive and -resistant human small cell lung carcinoma cell line

    NARCIS (Netherlands)

    de Jong, Steven; Mulder, N H; de Vries, Liesbeth; Robillard, G T

    1991-01-01

    P-31 nuclear magnetic resonance (NMR) spectra of cells and of cell extracts revealed high levels of phosphorylcholine (PC) and phosphocreatine (PCr) in an adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) and the adriamycin-sensitive parental cell line (GLC4). PCr levels in e

  16. Interactions between copper deficiency, selenium deficiency and adriamycin toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, J.; Tackett, R.; Johnson, M.A. (Univ. of Georgia, Athens (United States))

    1991-03-15

    The objective of this study was to test the hypothesis that there are interactions between copper (Cu) and selenium (Se) status, and adriamycin (ADR) toxicity. Male Sprague Dawley rats were fed Cu,Se adequate; Cu deficient, Se adequate ({minus}Cu); Cu adequate, Se deficient; or Cu,Se deficient diets for 38-41 days. ADR or saline (SAL) were administered weekly for the last 4 weeks of the study. Cu deficiency was confirmed by a 3-fold decrease in liver Cu,Zn-superoxide dismutase and liver Cu, and a 5-fold decrease in RBC Cu,Zn-SOD. Se deficiency was confirmed by a 10-fold decrease in liver glutathione peroxidase (GSH-Px). ADR, Cu deficiency and Se deficiency all caused EKG abnormalities. However, Cu and Se deficiencies did not enhance ADR's influence on EKGs. ADR increased lipid peroxidation in liver by 15% and in heart by 18% (NS). Cu deficiency decreased ADR-induced lipid peroxidation in heart tissue by 25%. ADR influenced Se status by significantly increasing heart GSH-Px, and Cu status by increasing liver Cu, plasma ceruloplasmin and liver Cu, Zn-SOD. These elevations in Cu,Zn-SOD and GSH-Px may be a consequence of the increased lipid peroxidation initiated by ADR. In {minus}Cu rats, ADR caused severe hemolytic anemia characterized by a 19% decrease in hematocrit and a 17-fold increase in splenic Fe. These data suggest that there are numerous interactions between ADR toxicity and Cu and Se status.

  17. Multiple impairments of cutaneous nociceptor function induced by cardiotoxic doses of Adriamycin in the rat.

    Science.gov (United States)

    Boros, Krisztina; Jancsó, Gábor; Dux, Mária; Fekécs, Zoltán; Bencsik, Péter; Oszlács, Orsolya; Katona, Márta; Ferdinandy, Péter; Nógrádi, Antal; Sántha, Péter

    2016-09-01

    Besides their deleterious action on cardiac muscle, anthracycline-type cytostatic agents exert significant neurotoxic effects on primary sensory neurons. Since cardiac sensory nerves confer protective effects on heart muscle and share common traits with cutaneous chemosensitive nerves, this study examined the effects of cardiotoxic doses of adriamycin on the function and morphology of epidermal nerves. Sensory neurogenic vasodilatation, plasma extravasation, and the neural CGRP release evoked by TRPV1 and TRPA1 agonists in vitro were examined by using laser Doppler flowmetry, the Evans blue technique, and ELISA, respectively. Carrageenan-induced hyperalgesia was assessed with the Hargreaves method. Immunohistochemistry was utilized to study cutaneous innervation. Adriamycin treatment resulted in profound reductions in the cutaneous neurogenic sensory vasodilatation and plasma extravasation evoked by the TRPV1 and TRPA1 agonists capsaicin and mustard oil, respectively. The in vitro capsaicin-, but not high potassium-evoked neural release of the major sensory neuropeptide, CGRP, was markedly attenuated after adriamycin treatment. Carrageenan-induced inflammatory hyperalgesia was largely abolished following the administration of adriamycin. Immunohistochemistry revealed a substantial loss of epidermal TRPV1-expressing nociceptive nerves and a marked thinning of the epidermis. These findings indicate impairments in the functions of TRPV1 and TRPA1 receptors expressed on cutaneous chemosensitive nociceptive nerves and the loss of epidermal axons following the administration of cardiotoxic doses of adriamycin. Monitoring of the cutaneous nociceptor function in the course of adriamycin therapy may well be of predictive value for early detection of the deterioration of cardiac nerves which confer protection against the deleterious effects of the drug. PMID:27342418

  18. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin.

    Science.gov (United States)

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-11-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  19. Effects of steroid sex hormones and adriamycin on human bladder cancer cells in culture.

    Directory of Open Access Journals (Sweden)

    Yoshimoto,Jun

    1982-02-01

    Full Text Available The effects of steroid sex hormones on the established cell lines derived from human urinary bladder cancer, T24, and from human transitional cell cancer of the urinary tract, 253J, were examined using the colony formation method. Of the seven kinds of steroid hormones tested, estradiol-17 beta was intensively cytotoxic for both cells. The cytotoxic effect was depended on the dose and time of treatment. The combined effect of Adriamycin and estradiol-17 beta on T24 cells could be recognized at low concentrations of Adriamycin (less than or equal to 10(-3 micrograms/ml after exposure for 24 h.

  20. Intraarterial versus intravenous adriamycin in the rabbit Vx-2 tumor system

    International Nuclear Information System (INIS)

    Intraarterial (IA) chemotherapy can theoretically result in a high tissue level of the drug with reduced systemic toxicity compared with intravenous (IV) administration. The authors compared these two modes of therapy using Adriamycin (doxorubicin) in the rabbit Vx-2 tumor system. Vx-2 implanted in hind limb muscle, and silastic catheters were placed in the jugular vein and femoral artery. Nuclear imaging of technetium-99m-labeled autologous erythrocytes in nine animals was used to measure the kinetics of tumor blood flow. Presence of tumor increased flow through the involved limb up to threefold. One minute following injection there was no difference in concentration of /sup 99m/Tc in tumor whether labeled cells were introduced IA or IV. Twelve rabbits received IA or IV Adriamycin (3 mg/kg), while eight animals received normal saline IA or IV as controls. Tumor progressed in all control rabbits, whereas there was an objective or complete response in 83% of animals receiving adriamycin. One hundred percent of those treated IA responded compared with 67% for IV. Median time to initial response in animals treated IA was 7 days versus 21 days for those treated IV. Thus, IA Adriamycin achieves a more complete and more rapid response than the drug given IV. This occurs despite a large tumor blood flow and rapid equilibrium using both methods

  1. CT-guided percutaneous adriamycin injection blocking foramen ovale in the treatment of trigeminal neuralgia

    International Nuclear Information System (INIS)

    Objective: To investigate the technique and clinical value of CT-guided percutaneous adriamycin injection blocking foramen ovale in the treatment of trigeminal neuralgia. Methods: Sixty-three patients (24 males, 39 females; the age ranged from 43 to 77 years with a mean of 59) with trigeminal neuralgia were treated with percutaneous adriamycin injection by CT-guided foramen ovale blocking therapy. All the patients were diagnosed with typical symptoms and had been treated by medicine, and 38 of them were also treated by other operation approaches (27 by chemical medicine blocking, 7 by radiofrequency thermocoagulation, and 4 by microvascular decompression). Results: All patients were successfully treated by CT-guided adriamycin blocking therapy. Adriamycin (0.2-0.5 ml) was slowly and fractionally injected when the tip was ascertained in ganglion of foramen ovale. Instant total pain relief was obtained in 61 cases (96.8%), obvious pain relief in 1 and slight relief in 1. After the initial procedure, pain relief rate at 6 and 12 months was 84.1% and 79.4% , respectively. No serious complications occurred. Conclusion: CT-guided percutaneous foramen ovale blocking therapy was a precise, non-painful, highly effective, mini-traumatic, and safe treatment, and it was also an alternative treatment to classic technique. (authors)

  2. Reversal effect of Dioscin on multidrug resistance in human hepatoma HepG2/adriamycin cells.

    Science.gov (United States)

    Sun, Bu Tong; Zheng, Li Hua; Bao, Yong Li; Yu, Chun Lei; Wu, Yin; Meng, Xiang Ying; Li, Yu Xin

    2011-03-01

    Multidrug resistance is a serious obstacle encountered in cancer treatment. Since drug resistance in human cancer is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a target for multidrug resistance reversion drug screening. In the present study, HEK293T cells were transfected with pGL3 reporter plasmids containing the 2kb of MDR1 promoter, and the transfected cells were used as models to screen for candidate multidrug resistance inhibitors from over 300 purified naturally occurring compounds extracted from plants and animals. Dioscin was found to have an inhibiting effect on MDR1 promoter activity. The resistant HepG2 cell line (HepG2/adriamycin) was used to validate the activity of multidrug resistance reversal by Dioscin. Results showed that Dioscin could decrease the resistance degree of HepG2/adriamycin cells, and significantly inhibit P-glycoprotein expression, as well as increase the accumulation of adriamycin in HepG2/adriamycin cells as measured by Flow Cytometric analysis. These results suggest that Dioscin is a potent multidrug resistance reversal agent and may be a potential adjunctive agent for tumor chemotherapy. PMID:21195709

  3. PLASMA-LIPOPROTEINS AND RENAL APOLIPOPROTEINS IN RATS WITH CHRONIC ADRIAMYCIN NEPHROSIS

    NARCIS (Netherlands)

    JOLES, JA; VANTOL, A; JANSEN, EHJM; KOOMANS, HA; RABELINK, TJ; VANGOOR, H

    1993-01-01

    The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progress

  4. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    International Nuclear Information System (INIS)

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation

  5. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shuyuan [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Chen, Jiaxi [The University of Texas Southwestern Medical Center at Dallas, Medical School, 5235 Harry Hine Blvd., Dallas, TX (United States); Huang, Pintong [Department of Ultrasonography, The 2nd Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province (China); Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Grayburn, Paul A., E-mail: paulgr@baylorhealth.edu [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Department of Internal Medicine, Division of Cardiology, Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall St, Suite H030, Dallas, TX (United States)

    2015-03-20

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation.

  6. The effect of multidrug resistance modulator HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in xenograft-nude mice.

    Science.gov (United States)

    Zhang, Yanyan; Feng, Yidong; Darshika, Kodithuwakku Nandani; Zhang, Bo; Hu, Yahui; Fang, Weirong; Li, Yunman; Huang, Wenlong

    2015-01-23

    To overcome MDR (multidrug resistance) of cancer mediated by P-gp (P-glycoprotein) has become a key strategy to improve the survival rate in clinic. Therefore, it is imperative to develop advanced modulators that have no side effects or interactions with cytotoxic drugs. HZ08, which acts as a P-gp inhibitor, shows a notable reverse effect with low cytotoxicity in vitro. Based on the previous results, the goal of this experiment is to elucidate the effect of HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in tumor-bearing nude mice. Several criterions and methods, such as tumor weight and volume, in vivo imaging, western blot, immunohistochemistry as well as ATPase hydrolysis assay were selected to evaluate the reversing activity and mechanism of HZ08 on MDR; Furthermore, fluorescence detection assay was applied to determine the distribution of adriamycin in the blood and tissues. This study revealed that HZ08 potentiated the anti-tumor activity of adriamycin but with little effect on the expression of P-gp in vivo. Adriamycin accumulation in tumor was enhanced by HZ08 via ATPase activity inhibition. In addition, HZ08 did not alter the pharmacokinetic characteristic of adriamycin in plasma or tissues. In conclusion, HZ08 showed dramatic MDR reversing activity and had no influence on the pharmacokinetics of adriamycin. PMID:25459530

  7. Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations

    OpenAIRE

    Coldwell, Kate E.; Cutts, Suzanne M.; Ognibene, Ted J.; Henderson, Paul T; Phillips, Don R.

    2008-01-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin–DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin–DNA adducts/104 bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin–DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We...

  8. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

    OpenAIRE

    Zhang, Shujuan; Feng ZHANG; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-01-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sym...

  9. Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Min Zheng

    Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

  10. Effects of adriamycin on respiratory chain activities in mitochondria from rat liver, rat heart and bovine heart. Evidence for a preferential inhibition of complex III and IV

    OpenAIRE

    Nicolay, K.; de Kruijff, B.

    1987-01-01

    The inhibition of respiratory chain activities in rat liver, rat heart and bovine heart mitochondria by the anthracycline antibiotic adriamycin was measured in order to determine the adriamycin-sensitive sites. It appeared that complex III and IV are efficiently affected such that their activities were reduced to 50% of control values at 175 ± 25 μM adriamycin. Complex I displayed a minor sensitivity to the drug. Of the complex-I-related activities tested, only duroquinone oxidation appeared ...

  11. Sequential radiotherapy and adriamycin in the management of bronchogenic carcinoma: the question of additive toxicity

    International Nuclear Information System (INIS)

    Intrapleural immunotherapy, radiotherapy and chemotherapy were employed in that sequence in 22 patients with Stage III non-oat cell bronchogenic carcinoma confined to the thorax. Seven patients received intrapleural BCG in a pilot study and 15 were randomized between intrapleural BCG and intrapleural saline. Isoniazid was begun on day 14 and irradiation (3000 rad in 10 fractions) to the primary lesion, mediastinum and ipsilateral supraclavicular nodes was started on day 21. One to two weeks following irradiation, CAMP chemotherapy was initiated (Cyclophosphamide 300 mg/M2 iv, d. 1,8; Adriamycin 20 mg/M2 iv, d. 1,8; Methotrexate 15 mg/M2 iv, d. 1,8 and Procarbazine 100 mg/M2 p.o., d. 1 to 10). Chemotherapy was given for a total of six months. Two patients expired prior to radiotherapy (1 tumor progression, 1 myocardial infarction) and 2 patients were lost to follow-up. Nausea, vomiting, alopecia and fatigue were universal side effects of the chemotherapy. Esophagitis occurred in 9 patients, 7 prior to and 2 after initiation of Adriamycin. In only one case did Adriamycin exacerbate a previous radiation esophagitis. No patient developed clinical radiation pneumonitis, although all had eventual radiation fibrosis. Congestive heart failure occurred in 1 patient with known valvular heart disease and responded to diuretics. Three patients developed localized herpes zoster infections. One patient developed radiation myelitis one year after initiating therapy and six months after completing all chemotherapy. The major side effect was leukopenia with relative platelet sparing. Although significant morbidity was encountered in this primarily older patient population (mean age 64.8 years) recall reactions involving irradiated intrathoracic structures were not a significant clinical problem

  12. Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo

    OpenAIRE

    Beckenlehner, Karin; Bannke, Silke; Spruss, Thilo; Bernhardt, Günther; Schönenberger, Helmut; Schiess, Wilfried

    1992-01-01

    The effect of hyaluronidase and a combination of hyaluronidase with Adriamycin was investigated on several breast cancer models in vitro and in vivo. In vitro enzyme treatment (using concentrations up to 80,000 IU/1) of murine (MXT-, MXT +/-, and MXT+) and human (MCF-7, ZR-75-1 and T-47-D) breast cancer cell lines did not inhibit tumour cell proliferation (measured by a kinetic crystal violet assay) in either case. Although high-dose hyaluronidase (1.2 x 10(6) IU/kg) was ineffective, when adm...

  13. Time dependent effects of Adriamycin and x-ray therapy on wound healing in the rat

    International Nuclear Information System (INIS)

    Wound healing as measured by wound breaking strength (WBS) was studied in male Fischer rats. Animals were wounded (day 0) and treated with Adriamycin (ADR), x-ray therapy (XRT), or the combination of ADR + XRT. Treatments were either on day -7,0 or +7. Animals were killed on days +14 and +21, and excised wounds were subjected to uniaxial extension and the recording of WBS (grams), hydroxy-proline assay, and collagen fiber diameter measurements. In this model, day 0 treatment with ADR, XRT, or ADR + XRT impaired WBS most significantly. This was supported by a diminution in newly synthesized hydroxyproline and load extension curve analysis

  14. Survival and kinetics of Chinese hamster ovary cell subpopulations induced by Adriamycin and radiation

    International Nuclear Information System (INIS)

    Mitotic selection of Chinese hamster ovary (CHO) cells, at 10 min intervals after the initiation of Adriamycin and/or x-ray treatment was used to measure the kinetics and survival of cells which progressed without delay, the ''refractory'' cells, the cells that reached mitosis only after recovery from the treatment-induced delay, the ''recovered'' cells, and the survival of the cells remaining attached to the flask 5 h after treatment. The cell kinetics were determined from the rate at which cells entered mitosis, and the reproductive integrity from the survival of the selected refractory, recovered and remaining (unselected) cells

  15. Tissue concentration of doxorubicin (adriamycin in mouse pretreated with alpha-tocopherol or coenzyme Q10.

    Directory of Open Access Journals (Sweden)

    Shinozawa,Shinya

    1991-06-01

    Full Text Available

    The tissue concentration of doxorubicin (adriamycin; ADM and its major metabolite (aglycone I was examined in mice pretreated with alpha-tocopherol (VE or coenzyme Q10 (CoQ. In VE-pretreated group, the concentrations of aglycone I of the liver (1, 3 and 5 h after the administration, kidney (1 and 3h and heart (3h were significantly higher than those in the saline group. The clinical application of VE or CoQ concomitant with anti-tumor drugs especially ADM, requires caution.

  16. Immunochemotherapy for advanced bladder cancer using FT-207, adriamycin and OK-432.

    Science.gov (United States)

    Mishina, T; Watanabe, H; Fujiwara, T; Kobayashi, T; Maegawa, M; Nakao, M; Nakagawa, S

    1982-10-01

    A combination therapy consisting of daily intrarectal administration of 1,500 mg of FT-207 suppository, daily or every three day bladder instillation of 40 mg adriamycin for a total of 20 applications, and once per week intramuscular administration of 5 KE OK-432 was described. The therapy was performed in 30 cases of advanced bladder cancer. The effectiveness evaluated by Karnofsky's criteria was as follows: 8 cases of 0-0, 2 of 0-A, 1 of 0-B, 2 of 0-C, 7 of 1-A and 10 of 1-B, showing an effective rate of 57%. Local pain was observed in 20 cases (67%), pancytopenia in 1 (3%), hepatitis in 4 (13%), stomatitis in 5 (17%) and anorexia in 6 (20%). From this clinical trial, it is presumed that combination therapy administering FT-207 intrarectally, adriamycin intravesically and OK-432 intramuscularly might be used for the treatment of advanced bladder cancer provided sufficient care is taken of general side effects. PMID:6817468

  17. Effect of eplerenone on serum TNF-α levels in adriamycin induced heart failure male rat models

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of eplerenone on serum TNF-α levels in adriamycin induced heart failure male rat models. Methods: Forty male rat models of adriamycin-induced heart failure were prepared with weekly intraperitoneal injection of adriamycin (4/mg/kg) for six weeks. Twenty surviving models were randomly divided into two groups: (1)eplerenone-treated group, n=10, treated with garage of eplerenone 200mg/kg/d for 12 weeks (2) non-treated group n=10. All the surviving models (group (1) n=8, group (2) n=6) were sacrificed after 12 weeks with left ventricular hemodynamic function parameters tested and serum TNF-α levels measured. Ten male rats without adriamycin administration served as controls. Results: Left ventricular hemodynamic parameters in the non-treated group were significantly worse than those in controls (P<0.05). The parameters in the eplerenone treated group were significantly better than those in the non-treated group (P<0.05). The serum TNF-α levels in the non-treated group were significantly higher than those in controls (P<0.05). TNF-α levels in the eplerenone group were significantly lower than those in the non-treated group (P<0.05). Conclusion: Eplerenone could reduce the serum TNF-α levels in the rat models of heart failure. (authors)

  18. Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts

    International Nuclear Information System (INIS)

    Previous investigators have demonstrated synergistic interaction between hyperthermia and radiation or Adriamycin (ADR), using cell lines that are sensitive to heat or ADR alone. The authors investigated the effect of heat, radiation or ADR on Chinese hamster fibroblasts (HA-1), their heat resistant variants and their ADR resistant variants. Heat for ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. While cells selected for ADR resistance were not cross resistant to heat, they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing combined modality trials

  19. Candida albicans--adriamycin interactions: ultrastructural and spectrofluorometric study of whole yeasts and spheroplasts.

    Science.gov (United States)

    Bobichon, H; Bussy, V; Angiboust, J F; Manfait, M; Bouchet, P; Jardillier, J C

    1990-01-01

    The occurrence of candidiasis in cancer patients who undergo chemotherapy requires the interrelation of Candida albicans and the antimitotic drug Adriamycin (ADM) which is well known as an intercalating agent. The whole yeasts were not affected by 2 h of contact with the drug at 10(-4) M neither for their growth curve nor for their ultrastructure, despite the presence of free ADM on their surface. Spheroplasts displayed a delay in their growth and exhibited altered nucleoli with segregation of their granular and fibrillar components. The modified emission spectrum of ADM, determined by spectrofluorometry, corresponded neither to the free ADM nor to the DNA-bound drug, but it could be related to a metabolite of the drug. The cell wall appeared to be one of the main sites for ADM resistance of Candida albicans in vitro. PMID:2085691

  20. Evaluation of adriamycin nephropathy by an in vivo electron paramagnetic resonance

    International Nuclear Information System (INIS)

    A rat model for human minimal change nephropathy was obtained by the intravenous injection of adriamycin (ADR) at 5 mg/kg. By using an in vivo electron paramagnetic resonance (EPR) spectrometer operating at 700 MHz, the temporal changes in signal intensities of a nitroxide radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), in the kidneys of rats with ADR nephropathy were investigated. The decay rate of the EPR signal intensity obtained in the kidney is indicative of the renal reducing ability. It was found that the reducing ability in the kidney declined on the 7th day after ADR administration and recovered after the 14th day. Impairment of the reducing ability occurred before the appearance of continuous urinary protein. The in vitro EPR study showed that this impairment of in vivo renal reducing ability is related to impairment of the reducing ability in the mitochondria

  1. A lack of Adriamycin (ADR) resistance in Chinese hamster ovary (CHO) cells overexpressing P-glycoprotein (Pgp) following in vitro exposure to fractionated X-irradiation

    International Nuclear Information System (INIS)

    Using x-ray pretreated CHO cells, the authors demonstrated differing accumulation of adriamycin and vincristine in cells overexpressing P-glycoprotein. Response was also varied by the addition of calcium channel antagonist verapamil. (author)

  2. 阿霉素改善三叉神经痛的疗效分析%Effect analysis of adriamycin on amelioration of trifacial neuralgia

    Institute of Scientific and Technical Information of China (English)

    熊懋昌; 史有亮

    2002-01-01

    @@ Backgroud:Trifacial neuralgia is a refractory disease.Radio-frequency,operation or blocking with anhydrous alcohol in Western medicine get no satisfying effect. Objective:To investigate the effect of adriamycin on amelioration of trifacial neuralgia.

  3. Neoadjuvant Chemotherapy with Ifosfamide, Cisplatin, Adriamycin and Mitomycin (IMAP for High risk Adult Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Mohagheghi Mohammad Ali

    2009-05-01

    Full Text Available To define efficacy of pre-operative chemotherapy in down staging of advanced non-round cell soft tissue sarcomas. From Sep 2002 to Dec 2005, 70 patients were treated by Ifosfamid, MESNA, cisplatin, adriamycin, mitomycin and subsequent surgery. Postoperatively, patients received radiotherapy in cases of microscopically incomplete resection or local recurrence. The median age of the patients was 34 years and the median tumor size was 14 cm. According to AJCC classification 46 patients had stage 3 and 24 had stage 4 diseases. The most common subtypes were MFH and leiomyosarcoma. The most common sites of tumors were lower extremity and trunk. Toxicity grades three or higher consisted of nausea, Leucopenia and infection. About 50% of the patients received G-CSF. Response to chemotherapy was assessable in 63 patients; 9 patients achieved complete response and 16 showed partial response. Disease progressed in 8 and did not change in 37. The best response was seen with MFH, fibrosarcoma and synovial sarcoma. After chemotherapy seventy percent of patients underwent complete surgery. Disease relapsed in 41 patients and twenty two patients died of metastasis. Median survival of patients was 30 months. IMAP plus G-CSF is safe and effective as preoperative chemotherapy in some subtypes of sarcomas, although the metastasis problem has not been eliminated

  4. The protective effects of methyl jasmonate against adriamycin--induced hepatic and renal toxicities.

    Science.gov (United States)

    Kosoko, A M; Molokwu, C J; Farombi, E O; Ademowo, O G

    2012-12-01

    The aim of the study was to investigate the protective effect of methyl jasmonate (MJ) in adriamycin (ADR) induced hepatic and renal toxicities. 36 BALB/c mice were randomly divided into control, ADR (20 mg/kg), MJ (50 mg/kg) only, MJ (100 mg/kg) only, MJ (50 mg/ kg) + ADR, MJ (100 mg/kg) + ADR groups (n = 6). The 2 doses of MJ was administered for 7 days in MJ only groups, ADR was administered intraperitoneally on the 8th day after pretreatment with the 2 different doses of MJ while ADR was administered on the 8th day only for the ADR only group. The malondialdehyde (MDA), glutathione (GSH), H2O2 generation, superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine in the liver, kidneys and serum samples as applicable were estimated. Tissue MDA, H2O2 generation, and GST activity were markedly elevated while GSH content, CAT and SOD activities were significantly reduced in the tissues when compared to the control (p inhibition of tissue peroxidative damage might contribute to this beneficial effect. PMID:23678646

  5. Evaluation of myocardiotoxicity with SPECT cardiac blood pool imaging for patients treated with adriamycin

    International Nuclear Information System (INIS)

    Evaluation of myocardiotoxicity on adriamycin (ADM) with SPECT cardiac blood pool imaging was presented. SPECT was done to monitor left ventricular function in 49 patients with Non-Hodgkin's Lymphoma and small cell carcinoma, they were treated with ADM of which the accumulation dose were over 300 mg/m2. The results showed that parameters of EF, PER and PFR before and after treatment with ADM were 57 +- 6%, 3.08 +- 0.63 EDV·s-1, 2.99 +- 0.23 EDV·s-1 and 50 +- 11%, 2.25 +- 0.66 EDV·s-1, 2.53 +- 0.35 EDV·s-1 respectively. The difference of these data are significant (P<0.05). The larger the accumulative dose of ADM, the more the parameters decrease, among them PFR is the most sensitive one. It was concluded that SPECT measurement of left ventricular function is a sensitive and useful method in monitoring ADM myocardiotoxicity

  6. Clinical usefulness of 123I-MIBG myocardial SPECT in patients with adriamycin-induced cardiomyopathy

    International Nuclear Information System (INIS)

    In 29 patients who had been administrated adriamycin (ADR) for the treatment of hematopoietic malignancies, myocardial SPECT was performed 20 minutes and 4 hours after an intravenous dose of 123I-metaiodobenzylguanidine (MIBG). Findings of the myocardial SPECT were compared with the total dose of ADR, ejection fraction (EF) and left ventricular wall motion, as assessed by ultrasound echocardiography. The mean total dose of ADR was 329.3 mg/m2 (range, 150-550 mg/m2). Although the cardiac function was normal, the washout rate (WR) of MIBG was high in 75% of the patients whose MIBG myocardial SPECT showed abnormality on ADR, suggesting the presence of adrenergic nerve disorder. The total dose of ADR was significantly correlated with WR of MIBG (p<0.001). Consequently WR of MIBG may be an index which reflects adrenergic nerve disorder in the myocardium earlier than EF. It was suggested that adrenergic nerve disorder was involved in pathogenesis of myocardial complications associated with ADR administration. In summary, MIBG myocardial SPECT could be a useful test for determining a dosage regimen of ADR therapy of individual patients. (author)

  7. CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

    Institute of Scientific and Technical Information of China (English)

    苏勇; 张锦明; 夏云飞; 朱荣; 钱朝南; 莫浩元

    2002-01-01

    Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

  8. Protection against adriamycin (doxorubicin-induced toxicity in mice by several clinically used drugs.

    Directory of Open Access Journals (Sweden)

    Shinozawa,Shinya

    1987-02-01

    Full Text Available Protective effects of clinically used drugs against adriamycin (ADM-induced toxicity were studied in ICR mice. The control mice, which were administered 15 mg/kg of ADM twice, survived 7.48 +/- 1.99 days (mean +/- S.D.. The survival times of mice treated with the following drugs, expressed as a percent of that of the control group, were 293.6% for coenzyme Q10 (Co Q10, 2 mg/kg, 402.2% for dextran sulfate (MDS, 300 mg/kg, 121.6% for flavin adenine dinucleotide (20 mg/kg, 236.3% for adenosine triphosphate disodium (50 mg/kg, 213.7% for reduced glutathione (100 mg/kg, 121.6% for phytonadione (50 mg/kg, 155.2% for inositol nicotinate (Ino-N, 500 mg/kg, 335.5% for nicomol (1000 mg/kg, 157.5% for nicardipine (10 mg/kg and 123.3% for dipyridamol (50 mg/kg. Anti-hyperlipemic agents such as MDS, nicomol, Ino-N and Co Q10 strongly protected against the ADM-induced toxicity, and the mice administered these drugs lived significantly longer than the control mice. The mechanism of the protective effect was discussed.

  9. The effect of adriamycin on dentinogenesis and 3H-thymidine incorporation into the enamel organ of the rat incisor

    International Nuclear Information System (INIS)

    The effect of adriamycin (5 mg/kg) on 3H-thymidine incorporation and on dentin formation was studied in rat incisors. Male Sprague Dawley rats received an intravenous injection of adriamycin. Some of these also received a subcutaneous injection of 3H-thymidine at a dose of 2 mCi/kg one day later. One group of control animals received an intravenous injection of a volume of physiological saline equal to that of the adriamycin dose. Another group received physiological saline, and one hour later was given an additional injection of 3H-thymidine at a similar dose as above. All the animals were killed 1 h, 1 d, 4 d, 8 d, 16 d, 28 d, and 32 d after 3H-thymidine treatment. Light microscopy revealed irregular dentin deposits between the mantle and circumpulpal layer of the labial dentin at 16 d. Within these deposits were trapped cells. The latter, through radioautographic labelling, appeared to be cells from the odontoblast layer. Also, the labelling pattern of the enamel organ in both the control and experimental groups indicated that the eruption rate of the tooth was not affected. Serial sectioning and examination of the lingual portion of the incisors at 28 d revealed a lack of dentin formation and a failure in the closure of the apical foramen. Electron microscopic observations showed an irregular and random arrangement of collagen fibers within the deposits of irregular dentin, and the presence of twisted odontoblastic processes. Examination of the lingual surface showed the presence of fibroblasts and collagen fibers bridging the gap that resulted from the failure in dentin formation. These cells, which were similar to periodontal ligament cells, appeared to have arisen from that area. (author)

  10. Interactions of radiation and adriamycin, bleomycin, mitomycin C or cis-diamminedichloroplatinum II in intestinal crypt cells

    DEFF Research Database (Denmark)

    von der Maase, H

    1984-01-01

    The interactions of radiation and adriamycin (ADM), bleomycin (BLM), mitomycin C (MM-C), or cis-diamminedichloroplatinum II (cis-DDP) in mouse jejunal crypt cells were studied using the microcolony survival assay. ADM administered from 24 h before to 48 h after irradiation resulted in an almost...... which interval the D0 surprisingly increased by a factor of 1.4. Administration of MM-C from 24 h before to 24 h after irradiation enhanced the radiation response. The effect peaked on administration 6 h before irradiation (DEF = 1.21) and diminished by application after irradiation. Cis-DDP enhanced...

  11. Adriamycin activity's durational governance of different cell death types and zonality in rat liver acinus. Immunohistochemical studies

    Directory of Open Access Journals (Sweden)

    Pedrycz Agnieszka

    2014-03-01

    Full Text Available The aim of this study was to develop and examine a model of apoptosis and necrosis of hepatocytes induced by a damaging factor - adriamycin, correlating time after its administration with cell death type, and to investigate the localisation within the liver acinus of hepatocytes dying in these two ways. The results obtained in the present and previous studies were compared in order to make a map of cell death localisation in the liver acinus, showing the effect of time in action and dose of adriamycin. The experiment was performed on 32 female Wistar rats, divided into four groups: I and II - experimental, and III and IV - control. Adriamycin (3 mg/kg b.w. was administered intraperitoneally to rats in groups I and II, and the rats were decapitated after four (group I and eight (group II weeks. Animals in control groups III and IV were given 0.5 mL of 0.9% NaCl solution, and decapitated after four and eight weeks respectively. Sections of the liver were examined with a three-stage immunohistochemical method. This method allowed to examine hepatocytes qualitatively and quantitatively for the presence of proteins involved in three types of apoptosis: induced by the mitochondrial pathway (caspase 3, 9, the intrinsic pathway related to endoplasmic reticulum stress (caspase 3, 12, and the extrinsic pathway (caspase 3, 8. One of the inflammatory markers, caspase 1, was also examined. The zonal localisation of all three types of apoptosis was assessed in the liver tissue. More oxidated hepatocytes indicated only signs of the internal mitochondrial pathway, whereas less oxidated hepatocytes induced the internal reticular pathway and the external apoptotic pathway. The period between adriamycin administration and hepatic cell investigation was a main factor of the process. A longer period post insult resulted in a more pronounced effect of the activation of apoptosis. Sections explored eight weeks after treatment with different doses of the drug (3 and 5

  12. A short-term in vitro test for tumour sensitivity to adriamycin based on flow cytometric DNA analysis

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1983-01-01

    A new method to test the sensitivity of tumour cells to chemotherapy is presented. Tumour cells were incubated in vitro on agar, and drug-induced cell cycle perturbation was monitored by flow cytometric DNA analysis. In the present study the method was applied to monitor the effect of adriamycin on...... resistant tumours. The dose level causing maximum accumulation in the G2 + M phase is suggested as a parameter for quantifying the sensitivity. The results indicate that the method can be extended to sensitivity testing of human tumours....

  13. Dioscin restores the activity of the anticancer agent adriamycin in multidrug-resistant human leukemia K562/adriamycin cells by down-regulating MDR1 via a mechanism involving NF-κB signaling inhibition.

    Science.gov (United States)

    Wang, Lijuan; Meng, Qiang; Wang, Changyuan; Liu, Qi; Peng, Jinyong; Huo, Xiaokui; Sun, Huijun; Ma, Xiaochi; Liu, Kexin

    2013-05-24

    The purpose of this study was to investigate the ameliorating effect of dioscin (1) on multidrug resistance (MDR) in adriamycin (ADR)-resistant erythroleukemic cells (K562/adriamycin, K562/ADR) and to clarify the molecular mechanisms involved. High levels of multidrug resistance 1 (MDR1) mRNA and protein and reduced ADR retention were found in K562/ADR cells compared with parental cells (K562). Dioscin (1), a constituent of plants in the genus Discorea, significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activity in K562/ADR cells. MDR1 mRNA and protein suppression resulted in the subsequent recovery of intracellular drug accumulation. Additionally, inhibitor κB-α (IκB-α) degradation was inhibited by 1. Dioscin (1) reversed ADR-induced MDR by down-regulating MDR1 expression by a mechanism that involves the inhibition of the NF-κB signaling pathway. These findings provide evidence to support the further investigation of the clinical application of dioscin (1) as a chemotherapy adjuvant. PMID:23621869

  14. Reversal of acquired resistance to adriamycin in CHO cells by tamoxifen and 4-hydroxy tamoxifen: role of drug interaction with alpha 1 acid glycoprotein.

    OpenAIRE

    Chatterjee, M.; Harris, A. L.

    1990-01-01

    Tamoxifen and 4-OH tamoxifen were used to reverse multidrug resistance (MDR) in CHO cells with acquired resistance to adriamycin (CHO-Adrr). Because alpha 1 acid glycoprotein (AAG) can bind a range of calcium channel blockers that also reverse MDR and rises in malignancy, its interactions with tamoxifen and 4-OH tamoxifen were also studied. Tamoxifen decreased the IC50 of 10 microM adriamycin 4.8-fold in the parent CHO-K1 cell line and 16-fold in CHO-Adrr. Similarly 4-OH tamoxifen decreased t...

  15. Combined radiotherapy and chemotherapy with cyclophosphamide, adriamycin, methotrexate, procarbazine (camp) in 64 consecutive patients with epidermoid bronchogenic carcinoma, limited disease: a prospective study

    International Nuclear Information System (INIS)

    Sixty-four consecutive patients with inoperable epidermoid bronchogenic carcinoma (limited disease) were treated with radiotherapy to the primary and nodal areas and combination chemotherapy with cyclophosphamide, adriamycin, methotrexate and procarbazine. The overall response rate (CR + PR) to combined treatment was 62%. The median survival time was 12.7 months. The toxicity was acceptable and no treatment-related death occurred

  16. Glutathione, glutathione S-transferases, and related redox enzymes in Adriamycin-resistant cell lines with a multidrug resistant phenotype.

    Science.gov (United States)

    Schisselbauer, J C; Crescimanno, M; D'Alessandro, N; Clapper, M; Toulmond, S; Tapiero, H; Tew, K D

    1989-01-01

    Friend erythroleukemia cells (FLC) selected by exposure to Adriamycin (doxorubicin) express an approximate 2.5-fold (ARN1) or 13-fold (ARN2) resistance to the drug with various degrees of cross-resistance to other anthracyclines, vinca alkaloids, and epipodophyllotoxins. Because the redox cycling of the quinone moiety of Adriamycin is known to produce oxidative stress, however, an analysis of glutathione (GSH) and related enzyme systems was undertaken in the wild-type and selected resistant cells. In ARN1 and ARN2, superoxide dismutase (SOD) and catalase activities were slightly decreased, intracellular GSH and GSH reductase were essentially unchanged, and total GSH peroxidase, glutathione S-transferase (GST), and DT-diaphorase activities were slightly elevated. In each case there was no stoichiometric relationship between degree of resistance and level of activity. GST isozymes were purified from each cell line by HPLC GSH affinity column chromatography. Two-dimensional gel electrophoresis and western blot immunoreactivity against a battery of GST isozyme polyclonal antibodies determined that both the resistant and sensitive cells expressed isozymes of the alpha, pi, and mu classes (alternative murine nomenclature: M1, M2, M3). Of significance, both ARN1 and ARN2 cell lines expressed a unique alpha subunit which was absent from the parent FLC cell line. This isozyme presumably accounted for the increased GSH peroxidase activity (cumene hydroperoxide as substrate) found in ARN1 and ARN2 and may play a role in the small incremental resistance to melphalan found for both resistant lines. Expression of the isozyme was not stoichiometric with respect to degree of resistance. The presence of this isozyme may contribute to the resistant phenotype or may be the consequence of a more general cellular response to oxidative stress. PMID:2639724

  17. Neph1 Is Reduced in Primary Focal Segmental Glomerulosclerosis, Minimal Change Nephrotic Syndrome, and Corresponding Experimental Animal Models of Adriamycin-Induced Nephropathy and Puromycin Aminonucleoside Nephrosis

    OpenAIRE

    Hulkko, Jenny; Patrakka, Jaakko; Lal, Mark; Tryggvason, Karl; Hultenby, Kjell; Wernerson, Annika

    2014-01-01

    Background/Aims The transmembrane proteins Neph1 and nephrin form a complex in the slit diaphragm (SD) of podocytes. As recent studies indicate an involvement of this complex in the polymerization of the actin cytoskeleton and proteinuria, we wanted to study the subcellular localization of Neph1 in the normal human kidney and its expression in focal segmental glomerulosclerosis (FSGS), minimal change nephrotic syndrome (MCNS), and the corresponding experimental models of Adriamycin-induced ne...

  18. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. I. Adriamycin

    International Nuclear Information System (INIS)

    Experiments have been carried out to determine the effect of different time intervals between x-irradiation (1200 rad) and the administration of Adriamycin (ADR) (6 mg/kg) on the growth delay produced in 3 mouse tumors. The tumors used were the EMT6/St/i.d. tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6/St/i.d. and RIF-1) treatment volume was used as the endpoint of response. The drug was administered by the intraperitoneal route either 24, 6, or 2 h before radiation, immediately before the start of radiation, or 3, 6, or 24 h after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level (close to the maximum tolerated dose), ADR alone produced only minimal growth delay in any of the tumors. Furthermore, the growth delays produced by drug/radiation combinations were not significantly different from the addition of the growth delays produced by the single modalities

  19. P-glycoprotein in adriamycin-resistant cells functions as an efflux pump for benzopyrene, a chemical carcinogen

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    Chao Yeh, G.; Poore, C.M.; Lopaczynska, J.; Phang, J.M. (NCI-FCRDC, Frederick, MD (United States))

    1991-03-15

    The physiological function of multidrug resistant gene (MDR 1) coded P-glycoprotein 170 (P-gp) in normal tissues remains unknown. The authors propose that P-gp functions as an efflux pump in normal tissues for benzopyrene and other xenobiotic substances. To examine their hypothesis the authors used a series of MDR human breast cancer MCF-7 cells with increasing degrees of drug resistance, expression of MDR and levels of P-gp. First, they found the IC{sub 50} for benzopyrene is linearly correlated with the levels of P-gp at different stages of adriamycin resistant MCF-7 cells. Using P-gp ({sup 3}H)azidopine labeling as a measurement of P-gp they found benzopyrene competes for labeling of P-gp. Finally, they directly measured cellular efflux of benzopyrene with adherent cell laser cytometry and found that resistant cells expressing high levels of P-gp showed rapid efflux of benzopyrene. By contrast, drug sensitive wild type cells with undetectable P-gp showed negligible efflux. They conclude that P-gp can function as an efflux pump for benzopyrene and suggest that P-gp may be a cellular mechanism for resistance to carcinogens.

  20. Effect of high dose alpha-tocopherol acetate on the toxicity and tissue distribution of adriamycin (doxorubicin.

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    Shinozawa,Shinya

    1988-10-01

    Full Text Available The effect of alpha-tocopherol acetate (VE on the toxicity and tissue distribution of adriamycin (ADM in mice was studied. After the administration of ADM in 2 doses of 15 mg/kg, mice pretreated with olive oil survived 7.1 +/- 1.0 days, while mice pretreated with VE in ten doses of 500 mg/kg/day (subcutaneously survived 5.5 +/- 1.7 days (p less than 0.01. The total concentration of ADM and its major metabolite, aglycone I in the liver (1, 3, 5 h, kidneys (1, 3 h, and heart (3 h, as determined by high performance liquid chromatography was significantly higher in the VE-pretreated group (four doses of 500 mg/kg/day than in the olive oil-pretreated group. The aglycone levels of the VE-pretreated group were significantly higher than those of the olive oil-pretreated group in the liver, kidney and heart, but there was no significant difference between the groups in the levels of the unmetabolized form. Considering these results, the administration of VE concomitant with anti-tumor drugs, including ADM, requires great caution.

  1. Chemoimmunotherapy of small cell bronchogenic carcinoma with VP-16-213, ifosfamide, vincristine, adriamycin, and Corynebacterium parvum

    International Nuclear Information System (INIS)

    Thirty-five consecutive patients with small cell bronchogenic carcinoma (SCBC) received chemoimmunotherapy with VP-16-213, Ifosfamide, vincristine, Adriamycin, and Corynebacterium parvum. Of 33 evaluable patients, 26 (79%) responded with complete (55%) or partial (24%) remissions. Complete remissions were more common among patients with limited disease (11/14 patients, 79%) compared with those with extensive disease (7/19 patients, 37%) and among patients (11/14 patients, 79%) compared with those with extensive disease (7/19 patients, 37%) and among patients who were ambulatory prior to therapy (16/25 patients, 64%) compared with those who were nonambulatory (2/8 patients, 25%). Myelosuppression consisted primarily of neutropenia. Eight percent of the treatment courses in 29% of the patients were associated with hematuria and/or documented episodes of infection during neutropenia. There were three deaths possibly related to treatment, in two of which there was no evidence of disease at post-mortem examination. Six patients relapsed in the central nervous system (CNS). In four instances, CNS relapse was the only site of tumor progression. Central nervous system relapse was more common among evaluable patients who did not receive prophylactic brain irradiation (5/17 patients, 29%, vs. 1/15 patients, 7%; P . 0.23). The median survival duration for all patients was 63 weeks, being slightly longer for patients with limited disease than for those with extensive disease (70.9 weeks vs. 56 weeks; P . 0.18). This was also true for patients who achieved complete rather than partial remissions (71 weeks vs. 50 weeks; P . 0.09). Patients receiving prophylactic brain irradiation experienced longer survival

  2. Enhanced antitumor effects of BPD-MA-mediated photodynamic therapy combined with adriamycin on breast cancer in mice

    Institute of Scientific and Technical Information of China (English)

    Zhong-sheng TONG; Pei-tian MIAO; Ting-ting LIU; Yong-sheng JIA; Xiao-dong LIU

    2012-01-01

    Aim:Photodynamic therapy (PDT) is an emerging treatment used to eradicate premalignant and early-stage cancers and to reduce tumor size in end-stage cancers.In this study,we investigated the effects of a combination of benzoporphyrin derivative monoacid ring A (BPD-MA)-mediated PDT with adriamycin (ADM) on 4T1 breast carcinoma cells in vivo and the mechanisms underlyingthis effect.Methods:Normal BALA/c female mice bearing 4T1 breast carcinoma xenografts were tested.The animals were treated with PDT (BPD-MA 1 mg/kg,iv,plus single-dose laser irradiation) or ADM (5 mg/kg,iv) alone,or a combination of PDT with ADM.The tumor growth rate was determined by measuring the tumor weight.Cell apoptosis was measured with flow cytometry,and the expression of apoptosis-related molecules was assessed using Western blot.Microvessel density (MVD) was determined with immunohistochemical staining.Results:Compared to PDT or ADM alone,PDT plus ADM produced a combined inhibition on the tumor growth,prolonged life span,and enhanced apoptosis in the mice bearing 4T1 subcutaneously xenografted tumors.The combination of PDT and ADM exerted additive effects on the upregulation of Bax and the downregulation of Bcl-2,and on the reduction of MVD in 4T1 xenografted tumors.Conclusion:Our results demonstrate that PDT plus ADM exerts enhanced in vivo antitumor effect on breast cancer,which is closely associated with the cooperative regulation of extrinsic apoptotic pathways and the inhibition of tumor angiogenesis.Thus,PDT plus ADM is a promising combined treatment strategy for breast carcinoma.

  3. Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse Model of Adriamycin-induced Nephropathy.

    Science.gov (United States)

    Min, Hye Sook; Cha, Jin Joo; Kim, Kitae; Kim, Jung Eun; Ghee, Jung Yeon; Kim, Hyunwook; Lee, Ji Eun; Han, Jee Young; Jeong, Lak Shin; Cha, Dae Ryong; Kang, Young Sun

    2016-09-01

    The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria. PMID:27510383

  4. [Liver abscess formation after treatment of liver cancer by arterial injection using adriamycin/mitomycin C oil suspension (ADMOS)].

    Science.gov (United States)

    Inoue, H; Hori, A; Satake, M; Kanetsuki, I; Ueno, K; Nishida, H; Ikeda, K; Kobayashi, H; Nakajo, M

    1992-02-25

    Of 210 patients with hepatocellular carcinoma (n = 135), metastatic liver cancer (n = 71) and cholangiocarcinoma (n = 4) who underwent intra-arterial infusion of adriamycin and/or mitomycin C oil suspension (ADMOS) and cisplatin, and both regimens, pyogenic liver abscess occurred in seven (3.3%). The percentages of abscess formation in the respective types of liver cancer were 0.8, 7.0 and 25%. These differences among the three types of liver cancer were attributed to the volume of the tumor vascular beds to be embolized, which might determine the relative amount or regional Lipiodol retention in the tumor and normal liver tissue. Four of seven patients with hepatic abscess had received the intra-arterial infusion of ADMOS, and their angiographic findings showed sequential decreases in the vascular beds of the tumor in comparison with those of previous infusion procedures; all had hypovascular liver tumors angiographically. We have never experienced this complication in other treatments such as embolization of the hepatic arteries and intra-arterial infusion of water-soluble anticancer drugs alone. These results suggest that the most important factor leading to abscess formation is the ischemic destruction of the intrahepatic ducts secondary to occlusion of the peribiliary arterial plexus by Lipiodol and/or the direct effects of anticancer drugs on these vessels. To avoid this complication, the volume of Lipiodol used for intraarterial infusion therapy should be carefully determined, especially when the patient has hypovascular tumors of the liver and a history of multiple previous intraarterial infusion procedures of anticancer drug. The use of ADMOS should be avoided in patients with hypovascular tumors of the liver such as secondary deposits and cholangiocarcinoma. PMID:1313961

  5. Effect of calcium antagonists and metabolic inhibitors on the retention of adriamycin, in both free and liposomal form, in a number of tumor cells lines

    International Nuclear Information System (INIS)

    Adriamycin (ADR) encapsulated in liposomes (MLV-ADR) accumulated at a lower rate, with a concomitant reduced cytotoxicity, in comparison to the free drug form (F-ADR) in all murine tumors tested. However, inhibition of [3H] thymidine incorporation into DNA appeared nearly equal between F-ADR and MLV-ADR treated tumor cells suggesting that the concentration necessary to inhibit DNA synthesis is only a fraction of the total drug content within the cells. Electrophoretic mobility of tumor cells was unaffected by exposure to either F-ADR or MLV-ADR. The metabolic inhibitor N-ethylmaleimide (NEM) when coincubated with F-ADR in P388 adriamycin-resistant leukemia cells (P388-ADR) resulted in a marked increase in intracellular drug accumulation. Use of the calcium channel blockers verapamil (VRP) and N-3,4-dimethoxyphenethyl)-N-methyl-2-(2-napthyl)-m-dithane-2-propylamine hydrochloride, (DMDP), a derivative of verapamil, in conjunction with adriamycin treatment demonstrated a near reversal of resistance in P388/ADR. Retention of drug increased 4-5 fold in the presence of each of the calcium antagonists in vitro studies with a concomitant drop in viability which surpassed that observed in P388/O. P388/ADR tumor bearing mice treated with the combination of VRP or DMDP and F-ADR exhibited no increase in mean survival times (MST) over F-ADR therapy alone. Scanning electron microscopy (SEM) studies of P388/O tumor cells demonstrated numerous, small villi-like processes, whereas P388/ADR cells possessed many large membraneous folds. Transmission electron microscopy (TEM) demonstrated not only the membrane folding seem by SEM, but also the presence of large numbers of C type viral particles in P388/ADR cells in comparison to the small amounts detected in P388/O cells

  6. Preparation of the core-shell structure adriamycin lipiodol microemulsions and their synergistic anti-tumor effects with diethyldithiocarbamate in vivo.

    Science.gov (United States)

    Daocheng, Wu; Mingxi, Wan

    2010-11-01

    We prepared the core-shell structure adriamycin lipiodol microemulsions (ADM-CSLMs) and evaluated their in vivo antitumor effects in combination with Diethyldithiocarbamate (DDC). Two types of ADM-CSLMs, adriamycin liposome-lipiodol microemulsion(ADM-LLM) and adriamycin microsphere lipiodol microemulsion (ADM-MLM), were prepared through the emulsification method. The drug loading and encapsulation efficiency of ADM-CSLMs were measured by the high-performance liquid chromatograph (HPLC). The size and shape of the ADM-CSLMs were determined by an atom force microscopy (AFM), a transmission electron microscopy (TEM), and a particle size analyzer, respectively. The synergistic effects of DDC and ADM-CSLMs for cancer treatment of carcinoma drug-resistance cell was evaluated by the MTT method, the activation of superoxide dismutase (SOD) was detected by chemiluminescence, and the ADM accumulation in cells was measured by flow cytometry. Walker-256 carcinoma was transplanted to the livers of the male SD rats, ADM-CSLMs were administrated to the livers of the rats by intervention hepatic artery embolization through microsurgery. The tumor growth and animal survival were evaluated. The results show that the average diameter of ADM-LLM and ADM-MLM were 4.23 ± 1.2 μm and 4.67 ± 1.4 μm, respectively, and their ADM encapsulation efficiency were 83.7% and 87.2% with respect to loading efficiency of 82 μg/ml and 91 μg/ml. The tumor growth and animal survival in two of the ADM-CSLMs combined with DDC groups were significantly higher than that of ADM only treatment, ADM liposome combined with DDC (P < 0.01), as well as the ADM microsphere combined with DDC (P < 0.01). Therefore, ADM-CSLMs are useful carriers for the treatment of carcinoma and their anti-tumor effect can be enhanced by DDC in a suitable concentration. PMID:20888179

  7. LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

    Science.gov (United States)

    Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

    2016-08-15

    Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. PMID:27336703

  8. Establishment by adriamycin exposure of multidrug-resistant rat ascites hepatoma AH130 cells showing low DT-diaphorase activity and high cross resistance to mitomycins.

    Science.gov (United States)

    Wakusawa, S; Nakamura, S; Miyamoto, K

    1997-01-01

    A resistant subline (AH130/5A) selected from rat hepatoma AH130 cells after exposure to adriamycin (ADM) showed remarkable resistance to multiple antitumor drugs, including mitomycin C (MMC) and porfiromycin (PFM). PFM, vinblastine (VLB), and ADM accumulated in AH130/5A far less than in the parent AH130 (AH130/P) cells. AH130/5A cells showed overexpression of P-glycoprotein (PGP), an increase in glutathione S-transferase activity, and a decrease in DT-diaphorase and glutathione peroxidase activity. The resistance to MMC and VLB of AH130/5A cells was partly reversed by H-87, an inhibitor of PGP. Buthionine sulfoximine, an inhibitor of glutathione synthase, did not affect the action of MMC. tert-Butylhydroquinone induced DT-diaphorase activity, increased PFM uptake, and enhanced the growth-inhibitory action of MMC in AH130/5A cells. Dicumarol, an inhibitor of DT-diaphorase, decreased PFM uptake and reduced the growth-inhibitory action of MMC in AH130/P cells. These results indicated that the adriamycin treatment of hepatoma cells caused multifactorial multidrug resistance involving a decrease in DT-diaphorase activity. PMID:9045901

  9. Evaluation of the secondary cardiotoxicity to use adriamycin in patients with breast cancer with nuclear medicine studies

    International Nuclear Information System (INIS)

    The number of surviving of cancer is increased highly with the current regimes of chemotherapy. For the year 2010 in U.S. it is considered that one of each 250 adults can be a survivor of wicked illness and many of these survivors will have been exposed to regimes with anthracycline. The anthracyclines concern to the group of antibiotics and they are effective point for hematological neoplasms as solid tumors. Although the relationship dose answer, among the regimes with anthracycline as well as the remission and the period free of illness is very established one, the latent risk of cardiotoxicity limits the use of these agents. Results: 30 patients were recruited with diagnostic of invader breast cancer tried with chemotherapy to base anthracycline in the understood period of may to december of the 2000. The medium of age it was of 48 years with a range of 27-80 years. The clinical stage that prevailed it was the EC IIB that represents a 36% in second place the EC IIIA with a 20%, EC IIA with 16% the EC IIIB and the unclassifiable ones represented 10% with 3 patients and finally the clinical stage IV with 8%, the most frequent localization was the left side.The received chemotherapy outline it was with the base of doxorubicin in its modality neo or patient adjutant, 5 patients also received taxanes like treatment adjutant. Prevailed the continuous infusion in 24 hours in 50%. The medium of accumulated dose of adriamycin was 274 mg/m2. With a left ventricular ejection fraction LVEF pretreatment of 62% (medium) determined by VRI and a medium of 69% by SPECT. The LVEF pos treatment had one medium of 57% for VRI and by SPECT a medium of 60%. They received concomitant radiotherapy with chemotherapy in modality pre operation 53.3% (16 patients), and 40% radiotherapy post operation, 2 patients didn't receive radiotherapy. In relation to the heart toxicity any patient present electrocardiographic alterations, neither arrhythmias neither clinical data of heart congestive

  10. Observation on FDG myocardial uptake in patients of lymphoma undergoing treatment with Adriamycin: can (18F)FDG-PET be an early marker of chemotherapeutic cardiotoxicity

    International Nuclear Information System (INIS)

    Full text: Adriamycin is a commonly used chemotherapeutic agent in patients with cancer, having cardiotoxicity as its main side effect. This effect is through generation of free radicals and mitochondrial damage. Adriamycin produces hypoxia and decreases synthesis of ATP molecules by aerobic oxidation. To meet this energy synthesis-demand deficit, glycolysis is favored. Hence such 'injured' myocardial cells switch over to glucose as their main source of energy. Neuregulins are a family of growth factors which exert cytoprotection in Adriamycin treated myocytes. Increased glycolysis is one of the downregulatory signal in this pathway. (18F)FDG is concentrated in the myocardial cells via Glut receptors and acts as a marker of glucose metabolism. Based on the above facts, we decided to study the effects of adriamycin on glucose metabolism in myocardium in vivo, with the help of 18F-FDG PET. Aim: To observe (18F)FDG myocardial uptake in patients of lymphoma undergoing treatment with Adriamycin. Materials and Methods: A retrospective analysis was done from the data of (18F)FDG PET scan of lymphoma patients who have completed anthracycline chemotherapy and underwent the said scan for their routine evaluation. The cardiac processing was done separately and a polar map (Bulls eye) generated from the SA slices of the myocardial tracer activity of these patients. Mean SUV value was calculated for the above-mentioned map. This mean SUV calculated in both pre- and post-chemotherapy scans was compared and analysed. Results: 18 patients (16M and 2F with mean age: 32.66 ± 14.81 years) of lymphoma who underwent pre- and post-doxorubicin therapy formed part of the study. The mean dose of doxorubicin received was 227.7 ± 116.59 mg/M2 of BSA. Three different groups were identified among these cases, 1) Group A showing increase in cardiac FDG uptake in post doxorubicin PET scan. Mean dose of doxorubicin received was 256.25 mg/m2 of BSA. 2) Group B showing fall in myocardial FDG

  11. Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells

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    Baoan Chen

    2008-06-01

    Full Text Available Baoan Chen1,5, Qian Sun1,5, Xuemei Wang2, Feng Gao1, Yongyuan Dai1, Yan Yin1, Jiahua Ding1, Chong Gao1, Jian Cheng1, Jingyuan Li2, Xinchen Sun1, Ningna Chen1, Wenlin Xu3, Huiling Shen3, Delong Liu41Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, China; 2State Key Lab of Bioelectronics(Chien-Shiung Wu Laboratory, Southeast University, Nanjing 210096, China; 3Department of Hematology, The First People’s Hospital of Zhenjiang, Zhenjiang, China; 4Westchester Medical Center, New York Medical College, NY, USA; 5These authors have contributed equally to this work.Abstract: Drug resistance is a primary hindrance for efficiency of chemotherapy. To investigate whether Fe3O4-magnetic nanoparticles (Fe3O4-MNPs loaded with adriamycin (ADM and tetrandrine (Tet would play a synergetic reverse role in multidrug resistant cell, we prepared the drug-loaded nanoparticles by mechanical absorption polymerization to act with K562 and one of its resistant cell line K562/A02. The survival of cells which were cultured with these conjugates for 48 h was observed by MTT assay. Using cells under the same condition described before, we took use of fluorescence microscope to measure fluorescence intensity of intracellular ADM at an excitation wavelength of 488 nm. P-glycoprotein (P-gp was analyzed with flow cytometer. The expression of mdr1 mRNA was measured by RT-PCR. The results showed that the growth inhibition efficacy of both the two cells increased with augmenting concentrations of Fe3O4-MNPs which were loaded with drugs. No linear correlation was found between fluorescence intensity of intracellular adriamycin and augmenting concentration of Fe3O4-MNPs. Tet could downregulate the level of mdr-1 gene and decrease the expression of P-gp. Furthermore, Tet polymerized with Fe3O4-MNPs reinforced this downregulation, causing a 100-fold more decrease in mdr1 mRNA level, but did not reduce total P-gp content. Our results suggest that Fe3O4-MNPs

  12. The growth of hemopoietic precursor cells (CFU-C) of adriamycin-treated or whole-body-irradiated dogs with or without bleomycin in vitro

    International Nuclear Information System (INIS)

    The effect of the cytostatic drug bleomycin (BLM) on the growth of canine hemopoietic stem-cells in vitro was tested in order to detect a stem-cell deficiency after in vivo-treatment with adriamycin (ADM) or whole-body-irradiation. Stem-cells damaged by irradiation or cytostatics are suppressed by bleomycin-induced strand-breaks in vitro. After stem-cell recovery the increased sensitivity towards bleomycin can no longer be detected. After whole-body-irradiation and cytostatical treatment the stem-cells who remained intact have to compensate the quantitative change of the stem-cells by increased proliferation. The proliferating cells show a particular bleomycin-sensitivity. Especially after irradiation a long persistence of the bleomycin-sensitivity can be reckoned on. (orig./MG)

  13. Effects of the Combined Use of Benazepril and Valsartan on Apoptosis in the Kidney of Rats with Adriamycin-induced Nephritic Glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    韩子明; 邢燕; 王宏伟; 梁秀玲; 周建华

    2004-01-01

    Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI)benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.

  14. Reversal effects of nomegestrol acetate on multidrug resistance in adriamycin-resistant MCF7 breast cancer cell line

    International Nuclear Information System (INIS)

    Chemotherapy is important in the systematic treatment of breast cancer. To enhance the response of tumours to chemotherapy, attention has been focused on agents to reverse multidrug resistance (MDR) and on the sensitivity of tumour cells to chemical drugs. Hundreds of reversal drugs have been found in vitro, but their clinical application has been limited because of their toxicity. The reversal activity of progestogen compounds has been demonstrated. However, classical agents such as progesterone and megestrol (MG) also have high toxicity. Nomegestrol (NOM) belongs to a new derivation of progestogens and shows very low toxicity. We studied the reversal activity of NOM and compared it with that of verapamil (VRP), droloxifene (DRO), tamoxifen (TAM) and MG, and investigated the reversal mechanism, i.e. effects on the expression of the MDR1, glutathione S-transferase Pi (GSTπ), MDR-related protein (MRP) and topoisomerase IIα (TopoIIα) genes, as well as the intracellular drug concentration and the cell cycle. The aim of the study was to examine the reversal effects of NOM on MDR in MCF7/ADR, an MCF7 breast cancer cell line resistant to adriamycin (ADR), and its mechanism of action. MCF7/ADR cells and MCF7/WT, an MCF7 breast cancer cell line sensitive to ADR, were treated with NOM as the acetate ester. With an assay based on a tetrazolium dye [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; MTT], the effects of various concentrations of NOM on MDR in MCF7/ADR cells were studied. Before and after the treatment with 5 μM NOM, the expression of the MDR-related genes MDR1, GSTπ, TopoIIα and MRP were assayed with a reverse transcriptase polymerase chain reaction (RT-PCR) immunocytochemistry assay. By using flow cytometry (FCM), we observed the intracellular ADR concentration and the effects of combined treatment with NOM and ADR on the cell cycle. Results collected were analysed with Student's t test. NOM significantly reversed MDR in MCF7/ADR

  15. The use of I-123 metaiodobenzylguanidine myocardial scintigraphy to evaluate the efficacy of olprinone hydrochloride in an experimental adriamycin-induced cardiomyopathy

    International Nuclear Information System (INIS)

    Adriamycin (ADR) has a strong antitumor effect on a number of malignant diseases, however, it can cause serious adverse effects, such as cardiac failure and fatal myocardial disorder. We evaluated the therapeutic effectiveness of olprinone hydrochloride (OH) and its ability to protect myocardium during ADR administration in a rabbit cardiomyopathy model. Twenty-seven 3-month-old male New Zealand white rabbits weighing 2.3-2.8 kg were placed in 4 groups: Group A (control group) received intravenous saline solution, 3 times a week for 8 weeks; Group B (cardiomyopathy model group) received intravenous injection of ADR 3 times per week for 8 weeks; Group C received daily ADR administration concurrently with OH intravenous administration for 8 weeks; and Group D received daily intravenous administration of OH which was begun 3 weeks after starting daily ADR administration. Electrocardiography, hematologic and biochemical examination, echocardiography, myocardial scintigraphy (123I-m-iodobenzylguanidine (MIBG)) and histopathological examination were used to evaluate each group and the results were compared. The incidence of myocardical disorder caused by ADR was lower in Group C, as compared with Group B. However, there were no differences between groups D and B. Our findings show that when OH administration began at the same time as ADR administration, it inhibited ADR-induced cardiomyopathy, and possibly prevented heart failure, thanks to its protective effect on the myocardium. (author)

  16. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  17. Effects of fructose-1,6-diphosphate on concentration of calcium and activities of sarcoplosnic Ca2+-ATPase in cardiomyocytes of Adriamycin-treated rats

    Institute of Scientific and Technical Information of China (English)

    CAI Wei; CHEN Jun-zhu; RUAN Li-ming; WANG Yi-na

    2005-01-01

    Objective: To observe the effects of fructose-1,6-diphosphate (FDP) on serum levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB), as well as the concentration of calcium in cardiomyocytes (Myo[Ca2+]) and activity of sarcoplosnic Ca2+-ATPase (SRCa2+-ATPase) in Adriamycin (ADR)-treated rats. Methods: Rats were intraperitoneally injected with ADR (2.5mg/kg every other day for 6 times) and then with different dosages of FDP (every other day for twenty-one times). Bi-antibodies sandwich Enzyme linked immune absorption assay (ELISA) was performed to detect serum level of cTnI. CK-MB was detected by monoclonal antibody, Myo[Ca2+] was detected by fluorescent spectrophotometry and the activity of SRCa2+-ATPase was detected by inorganic phosphate method. Results: FDP (300, 600, 1200 mg/kg) significantly reduced the serum levels of cTnI and CK-MB, while at the same time decreased calcium concentration and increased SRCa2+-ATPase activity in cardiomyocytes of ADR-treated rats (P<0.01). Conclusions: FDP might alleviate the cardiotoxic effects induced by ADR through decreasing calcium level as well as increasing SRCa2+-ATPase activity in cardiomyocytes.

  18. Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1.

    Science.gov (United States)

    Wang, Changyuan; Huo, Xiaokui; Wang, Lijuan; Meng, Qiang; Liu, Zhihao; Liu, Qi; Sun, Huijun; Sun, Pengyuan; Peng, Jinyong; Liu, Kexin

    2016-01-01

    The purpose of present study was to investigate the effect of dioscin on activity of adriamycin (ADR) in ADR-sensitive (MCF-7) and ADR-resistant (MCF-7/ADR) human breast cancer cells and to clarify the molecular mechanisms involved. Antiproliferation effect of ADR was enhanced by dioscin in MCF-7 and MCF-7/ADR cells. Dioscin significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activity in MCF-7/ADR cells. Additionally, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Moreover, dioscin induced the formation of vacuoles in the cytoplasm and protein level of LC3-II in MCF-7 and MCF-7/ADR cells. Autophagy inhibitor 3-MA abolished the effect of dioscin on ADR cytotoxicity. Dioscin inhibited phosphorylation of PI3K and Akt, resulting in upregulation of LC3-II expression. In conclusion, dioscin increased ADR chemosensitivity by down-regulating MDR1 expression through NF-κB signaling inhibition in MCF-7/ADR cells. Autophagy was induced by dioscin to ameliorate the cytotoxicity of ADR via inhibition of the PI3K/AKT pathways in MCF-7 and MCF-7/ADR cells. These findings provide evidence in support of further investigation into the clinical application of dioscin as a chemotherapy adjuvant. PMID:27329817

  19. The labelling of adriamycin-loaded human serum albumin immuno-nanoparticles led by monoclonal antibodies with 131I and its anti-hepatoma effect in vivo

    International Nuclear Information System (INIS)

    The pharmaceutics character, targeting to hepatoma and anticancer activity in nude mice of adriamycin-loaded human serum albumin immuno-nanoparticles (ADR-HSA-NP) against hepatoma led by anti-human hepatoma monoclonal antibodies HAb18 are studied. The results show that effective loaded drug dose of HAb18-ADR-HSA-NP is 1.44%, which is lower than ADR-HSA-NP (1.69%); HAb18-ADR-HSA-NP slowly releases drug ADR and its maximum releasing drug dose (41%) is obviously lower than ADR-HSA-NP (65%) (P 131I-HAb18-ADR-HSA-NP mainly accumulates in liver and its liver-taxis and stability are better than 131I-ADR-HSA-NP in nude mice by intravenous injection; HAb18-ADR-HSA-NP mainly accumulates in tumor and its accumulation amount of tumor is higher than ADR-HSA-NP (P < 0.05), and has obvious inhibiting cancer action and its inhibitory rate of cancer is also higher than ADR-HSA-NP (P < 0.05) by tumor injection. So, HAb18-ADR-HSA-NP can bind and inhibit hepatoma cell from growing in vivo

  20. miR-222 confers the resistance of breast cancer cells to Adriamycin through suppression of p27(kip1) expression.

    Science.gov (United States)

    Wang, Dan-Dan; Li, Jian; Sha, Huan-Huan; Chen, Xiu; Yang, Su-Jin; Shen, Hong-Yu; Zhong, Shan-Liang; Zhao, Jian-Hua; Tang, Jin-Hai

    2016-09-15

    Adriamycin (Adr) is a potent chemotherapeutic agent for chemotherapy of breast cancer patients. Despite impressive initial clinical responses, some developed drug resistance to Adr-based therapy and the mechanisms underlying breast cancer cells resistance to Adr are not well known. In our previous study, in vitro, we verified that miR-222 was upregulated in Adr-resistant breast cancer cells (MCF-7/Adr) compared with the sensitive parental cells (MCF-7/S). Here, miR-222 inhibitors or mimics were transfected into MCF-7 cell lines. RT-qPCR and western blot were used to detect the expression of p27(kip1). Immunofluorescence showed that miR-222 altered the subcellular location of p27(kip1) in nucleus. MTT was employed to verify the sensitivity of breast cancer cell lines to Adr. Flow cytometry showed the apoptosis and cell cycles of the cells after adding Adr. The results showed that downregulation of miR-222 in MCF-7/Adr increased sensitivity to Adr and Adr-induced apoptosis, and arrested the cells in G1 phase, accompanied by more expressions of p27(kip1), especially in nucleus. Furthermore, overexpressed miR-222 in MCF-7/S had the inverse results. Taken together, the results found that miR-222 induced Adr-resistance at least in part via suppressing p27(kip1) expression and altering its subcellular localization, and miR-222 inhibitors could reverse Adr-resistance of breast cancer cells. These results disclosed that the future holds much promise for the targeted therapeutic in the treatment of Adr-resistant breast cancer. PMID:27282281

  1. Cell size and geometry of spinal cord motoneurons in the adult cat following the intramuscular injection of adriamycin: comparison with data from aged cats.

    Science.gov (United States)

    Liu, R H; Yamuy, J; Engelhardt, J K; Xi, M C; Morales, F R; Chase, M H

    1996-10-28

    Adriamycin (ADM), an antineoplastic antibiotic, when injected intramuscularly, is taken up by motoneuron axonal terminals and retrogradely transported to the motoneuron soma where it exerts its neurotoxic effect. In the present study, ADM was injected into the hindlimb muscles of five adult cats. Measurements of the electrophysiological properties of the lumbar motoneurons innervating these muscles were obtained using intracellular techniques. Based upon these data the equivalent cylinder model of motoneurons was employed to evaluate ADM-induced changes in cell size and cell geometry. The size of cell somas in the ventral horn was also measured using light microscopy and computer imaging software. There were significant increases in the membrane time constant (25%) and input resistance (50%) in motoneurons whose muscles were treated with ADM (ADM-MNs) compared with data from control motoneurons (control-MNs). The increase in membrane time constant is attributed to an increase in membrane resistance; the increase in input resistance appears to depend upon both an increase in membrane resistance and a decrease in total cell surface area. Cell capacitance, which is proportional to the total cell surface area, was significantly reduced (15%) in ADM-MNs. Calculations based on cable theory indicate that while there was no significant change in the length of the equivalent cylinder for ADM-MNs, there was a significant decrease (17%) in the diameter of the equivalent cylinder. These data indicate that there is a decrease in total cell surface area which can be attributed to the shrinkage of branches throughout the dendritic tree. There was also a small (7%) but statistically significant decrease in the electrotonic length of ADM-MNs. Morphological analysis also revealed that the mean cross-sectional area of the somas of those ventral horn neurons which are likely to correspond to the motoneuron population was significantly reduced on the ADM-treated side compared to that

  2. Changes in the electrophysiological properties of cat spinal motoneurons following the intramuscular injection of adriamycin compared with changes in the properties of motoneurons in aged cats.

    Science.gov (United States)

    Liu, R H; Yamuy, J; Xi, M C; Morales, F R; Chase, M H

    1995-11-01

    1. This study was undertaken to investigate the effects of adriamycin (ADM, Doxorubicin) on the basic electrophysiological properties of spinal cord motoneurons in the adult cat. ADM was injected into the biceps, gastrocnemius, semitendinosus, and semimembranosus muscles of the left hindlimb (1.2 mg per muscle). Intracellular recordings from motoneurons innervating these muscles were carried out 12, 20, or 40 days after ADM administration and from corresponding motoneurons in untreated control cats. 2. Twelve days after ADM injection, motoneurons innervating ADM-treated muscles (ADM MNs) exhibited statistically significant increases in input resistance, membrane time constant, and amplitude of the action potential's afterhyperpolarization (AHP). In addition, there was a statistically significant decrease in rheobase and in the delay between the action potential of the initial segment (IS) and that of the somadendritic (SD) portion of the motoneuron (IS-SD delay). There were no significant changes in the resting membrane potential, threshold depolarization, action potential amplitude, or axonal conduction velocity. 3. The changes in electrical properties of motoneurons at 20 and 40 days after ADM injection were qualitatively similar to those observed at 12 days. However, at 40 days after ADM injection there was a statistically significant decrease in the axonal conduction velocity of the ADM MNs. 4. The normal correlations that are present between the AHP duration and electrical properties of the control motoneurons were observed in the ADM MNs, e.g., AHP duration was positively correlated with the input resistance and time constant and negatively correlated with the axonal conduction velocity. The correlation coefficients, however, were reduced in comparison with the control data. 5. This study demonstrates that ADM exerts significant effects on the electrical properties of motoneurons when injected into their target muscles. The majority of the changes in

  3. Synergistic antitumoral activity and induction of apoptosis by novel pan Bcl-2 proteins inhibitor apogossypolone with adriamycin in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jin-xia MI; Guang-feng WANG; Heng-bang WANG; Xiao-qing SUN; Xin-yan NI; Xiong-wen ZHANG; Jia-ming TANG; Da-jun YANG

    2008-01-01

    Aim: To investigate the in vitro and in vivo activities and related mechanism of apogossypoione (ApoG2) alone or in combination with adriamycin (ADM) against human hepatocellular carcinoma (HCC). Methods: The IC50 of ApoG2 in vitro was tested by WST assay, and the synergistic effect was analyzed using the CalcuSyn method. Cell apoptosis was determined using 4',6-diamidino-2-phenylindole staining and flow cytometric analysis. Western blotting was used to determine the expression of apoptosis-related proteins. In vivo activity was evaluated in the xenograft model in nude mice, and apoptosis in tumor tissues was determined by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) assay. Results: The IC50 of ApoG2 in HCC cells was 17.28-30.63 μmol/L. When ApoG2 was combined with ADM, in-creased cytotoxicity and apoptosis were observed in SMMC-7721 cells compared to treatment with ApoG2 alone. The Western blotting results indicated that the ApoG2 induced apoptosis in SMMC-7721 cells by downregulating anti-apoptotic proteins Bcl-2, Mcl-1, and Bcl-XL, up-regulating pro-apoptotic protein Noxa, and promoting the activities of caspases-9 and -3. The tumor growth of xenograft SMMC-7721 was inhibited in nude mice when ApoG2 was administered orally without causing damage to the normal tissues. The in vivo study also indicated an increasing anti-tumoral effect when ApoG2 at 100 or 200 mg/kg dosages were used together with ADM at 5.5 mg/kg, with relative tumor proliferation rate (T/C) values of 0.456 and 0.323, respectively. Apoptosis induced in vivo by ApoG2 alone or combined with ADM was confirmed by TUNEL assay in tumor tissues. Conclusion: ApoG2 is a potential non-toxic target agent that induces apoptosis by upregulating Noxa, while inhibiting anti-apoptotic proteins and pro-moting the effect of chemotherapy agent ADM in HCC.

  4. Use of laser photomodulation in the evolution of oral mucositis associated to cyclophosphamide, methotrexate, 5-fluouracil - CMF in 5 fluouracil + adriamycin + cyclophosphamide - FAC chemotherapy protocols in patients with breast cancer

    Science.gov (United States)

    de Fátima Lima Ferreira, Maria; de Carvalho, Fabiola Bastos; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Santos, Gustavo M. P.; Gesteira, Maria F. M.; Maia, Tereza Cristina Teixeira; Pinheiro, Antônio L. B.

    2013-03-01

    The aim of this study was to evaluate the efficacy of the laser photobiomodulation (FBML) in prevention and treatment of oral mucositis induced by chemotherapy protocols CMF (cyclophosphamide, methotrexate, 5-Fluouracil) and FAC (5 Fluouracil + Adriamycin + Cyclophosphamide) in cancer patients breast. We selected 28 patients treated at the Center for High Complexity (CACON), who underwent 6 cycles of 21 days of treatment, with diagnosis of infiltrating ductal carcinoma (ICD C50.9). Were randomly divided into three groups: Group A - eight patients (Protocol FAC + Dental protocol of CACON + Laser), Group B - 6 patients (Protocol CMF + Dental protocol of CACON + Laser), Group C - was divided into two sub-groups: Group C1 with 8 patients (Control Group 1: FAC + Dental protocol o CACON) and group C2 with 6 patients (control group 2: Protocol CMF + Dental protocol of CACON). Patients in Group A and B were use of preventive FBML 24 hours before the start of chemotherapy cycle, then every 48 hours and was extended up to one week following completion of chemotherapy. The groups A and B, presented oral mucositis grade 0 (64.29%) p = 0.07, grade I (7.14%), grade II (14.29%), grade III (7.14 %), grade IV (7.14%) compared to group C, who presented mucositis grade 0 (35.71%) in the initial evaluation with p = 0.10, grade I (21.43%), grade II (28.57%), grade III (14.29%), grade IV (0.00%), patients who used the FBML as a preventive and therapeutic showed a reduction and pain relief in 42.86%. It is concluded that the low power laser when used preventively or as therapy and showed immediate relief of pain and accelerate tissue repair.

  5. Experimental study on proteomics of rats with adriamycin-induced nephropathy by tonifying the kidney and promoting blood circulation%益肾活血法干预阿霉素肾病大鼠蛋白质组学的实验研究

    Institute of Scientific and Technical Information of China (English)

    艾斯; 郑健; 林青; 吴华嵩; 陈蓉艳; 陈文列

    2011-01-01

    目的:应用蛋白质组学筛选阿霉素肾病(AN)大鼠血清中差异表达的蛋白质,旨在蛋白质分子水平探索原发性肾病综合征(PNS)的诊断标志物及益肾活血中药肾康灵治疗的作用靶点.方法:实验分为正常组(A组)、AN病模组(B组)、AN病模+泼尼松组(C组)、AN病模+肾康灵组(D组)、AN病模+泼尼松+肾康灵组(E组).利用表面增强激光解析-电离飞行时间质谱(SELDI-TOF-MS)联合CM10蛋白质芯片技术检测各组大鼠血蛋白质组质谱的表达,采用PBS Ⅱ-C型蛋白质芯片阅读机自动收集数据.结果:在质荷比值(M/Z)2 000-50 000 Da范围内,P<0.05.质谱仪筛选出B组与A组比较的11种差异蛋白,其中4种差异蛋白在B组中高表达,7种蛋白低表达;蛋白峰 9069、15005、15047Da在B、C、D、E组问比较有显著差异,经鉴定可能分别为Cortexin-1、Interleukin-17A、Podoplanin,其中蛋白峰15005、15047从B组→C组→D、E组→A组呈递减趋势,蛋白峰9069呈递增趋势.结论:SELDI-TOF-MS能有效分析阿霉素肾病大鼠血清蛋白质质谱,益肾活血中药肾康灵干预治疗后蛋白质质谱表达有显著差异.%objective: To analyze the blood proteomic patterns of rats with adriamycin- induced nephropathy by blood proteomics, for discussing the biomarker of primary nephrotic syndrome and target point of medication. Methods: Rats were divided into normal rats (group A), adriamycin-induced nephropathy rats (group B), adriamycin- induced nephropathy rats and prednisone (group C), adriamycin- induced nephropathy rats and prednisone and Shenkangling (clinical density) (group D),adriamycin- induced nephropathy rats and prednisone and Shenkangling (double clinical density) (group E).Surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) CM10 protein clips was used to detect the blood proteomic patterns of every rat,PBS Ⅱ-C protein clips reading machine was applied to collect data

  6. 钩藤碱对阿霉素诱导的大鼠肾损伤的作用及其机制%Effects of rhynchophylline on adriamycin-induced renal injury in rats

    Institute of Scientific and Technical Information of China (English)

    龙吉美; 黄德彬; 李魁武; 罗琼

    2012-01-01

    目的:探讨钩藤碱(rhynchophylline,RHL)对阿霉素致大鼠肾功能损伤的作用及其机制.方法:将52只雌性SD大鼠随机分为生理盐水组(NSG,n=10)、模型组(MG,n=14)、钩藤碱低剂量治疗组(RHL-LG,n=14)和高剂量治疗组(RHL-HG,n=14).后3组经尾静脉注射阿霉素(5 mg·kg-1)建立肾病模型,NSG注射等容量生理盐水(NS);2周后,RHL-LG和RHL-HG分别给予腹腔注射RHL 5mg·kg-1和15mg·kg-1,NSG和MG分别给予等容量NS.8周后采集血、尿及肾组织标本,检测尿蛋白、血尿素氮(BUN)、血清肌酐 (SCr)、组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,进行肾组织病理学观察,RT-PCR检测肾组织中血管紧张素Ⅱ受体1、2(AT1,2-R)、血管紧张素转换酶(ACE)及血管紧张素原(AGT)mRNA的表达.结果:MG的蛋白尿、BUN、SCr和MDA含量明显高于NSG 、RHL-LG和RHL-HG(P<0.05),而以RHL-HG的BUN、SCr和MDA含量降低得最为明显;RHL-HG的SOD活性明显高于RHL-LG和MG(P<0.05);MG肾组织病理损伤严重,而RHL-LG和RHL-HG损伤程度明显减轻,RHL-HG轻于RHL-LG;MG肾组织中的AT1-R、ACE和AGT mRNA表达均显著高于RHL-LG,而RHL-LG显著高于RHL-HG(P<0.05),MG AT2-R mRNA表达显著低于RHL-LG,RHL-LG则显著低于RHL-HG(P<0.05).结论:RHL能减缓阿霉素所致的大鼠肾功能损伤,其机制可能与其减轻肾脏脂质过氧化损伤,调控肾组织中AT1,2-R、ACE和AGT mRNA的表达,增加肾血流量等因素有关.%AIM; To explore the effects of rhynchophylline (RHL) on rat renal injury induced by adriamycin. METHODS: Fifty - two female SD rats were randomly divided into normal saline group (NSG, n = 10) , model group ( MG, n = 14) , low - dose RHL treatment group ( RHL - LG, n = 14) and high - dose RHL treatment group ( RHL - HG, n = 14). The animals in the latter 3 groups were injected with adriamycin at a dose of 5 mg/kg through the tail vein. The animals in RHL - LG and RHL - HG were treated with RHL at doses of 5 mg/kg and 15 mg

  7. Evaluation of the secondary cardiotoxicity to use adriamycin in patients with breast cancer with nuclear medicine studies; Evaluacion de la cardiotoxicidad secundaria al empleo de adriamicina en pacientes con cancer de mama con estudios de medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Garcia P, S

    2003-07-01

    The number of surviving of cancer is increased highly with the current regimes of chemotherapy. For the year 2010 in U.S. it is considered that one of each 250 adults can be a survivor of wicked illness and many of these survivors will have been exposed to regimes with anthracycline. The anthracyclines concern to the group of antibiotics and they are effective point for hematological neoplasms as solid tumors. Although the relationship dose answer, among the regimes with anthracycline as well as the remission and the period free of illness is very established one, the latent risk of cardiotoxicity limits the use of these agents. Results: 30 patients were recruited with diagnostic of invader breast cancer tried with chemotherapy to base anthracycline in the understood period of may to december of the 2000. The medium of age it was of 48 years with a range of 27-80 years. The clinical stage that prevailed it was the EC IIB that represents a 36% in second place the EC IIIA with a 20%, EC IIA with 16% the EC IIIB and the unclassifiable ones represented 10% with 3 patients and finally the clinical stage IV with 8%, the most frequent localization was the left side.The received chemotherapy outline it was with the base of doxorubicin in its modality neo or patient adjutant, 5 patients also received taxanes like treatment adjutant. Prevailed the continuous infusion in 24 hours in 50%. The medium of accumulated dose of adriamycin was 274 mg/m{sup 2}. With a left ventricular ejection fraction LVEF pretreatment of 62% (medium) determined by VRI and a medium of 69% by SPECT. The LVEF pos treatment had one medium of 57% for VRI and by SPECT a medium of 60%. They received concomitant radiotherapy with chemotherapy in modality pre operation 53.3% (16 patients), and 40% radiotherapy post operation, 2 patients didn't receive radiotherapy. In relation to the heart toxicity any patient present electrocardiographic alterations, neither arrhythmias neither clinical data of heart

  8. siRNA沉默c-FLIP对K562/ADR耐药性的影响%Effect of siRNA-mediated silencing of c-FLIP on adriamycin-resistance of K562/ADR cells

    Institute of Scientific and Technical Information of China (English)

    宋敏; 王建宁; 孟庆齐; 包红雨; 杨杰

    2015-01-01

    目的:探讨c-FLIP siRNA干扰c-FLIP mRNA水平对阿霉素耐药细胞K562/ADR的耐药性的影响及作用机制。方法应用siRNA干扰的方法抑制K562及K562/ADR细胞c-FLIP的表达,通过荧光定量PCR的方法检测c-FLIP mRNA表达及对多药耐药基因MDR1 mRNA水平的影响。MTT法检测c-FLIP干扰与否对K562及K562/ADR细胞增殖的影响,Annexin V/7-ADD双染研究c-FLIP干扰与否对K562及K562/ADR细胞凋亡的影响。结果与阴性siRNA转染组相比较,c-FLIP siRNA转染下调K562细胞中c-FLIP的mRNA后,K562细胞增殖受到一定程度的抑制(P<0.05),但是并未显著诱导细胞凋亡,c-FLIP干扰与否K562细胞48 h增殖率分别为(69.14±1.82)%和(60.69±2.23)%,凋亡率分别为(1.7±0.3)%和(1.8±0.2)%。与阴性siRNA转染组相比较, c-FLIP siRNA转染抑制K562/ADR细胞中c-FLIP的mRNA后,K562/ADR细胞增殖显著被抑制(P<0.05),并显著诱导了细胞凋亡增加(P<0.05),c-FLIP干扰与否K562/ADR细胞48 h增殖率分别为(-6.07±0.71)%和(-37.45±3.53)%,凋亡率分别为(5.2±0.4)%和(9.2±0.4)%。并且c-FLIP siRNA下调c-FLIP mRNA水平后,K562/ADR细胞中的多药耐药基因MDR1的mRNA表达水平也被显著下调(P<0.05)。结论 c-FLIP siRNA下调K562/ADR细胞中c-FLIP的mRNA水平抑制了多药耐药基因MDR1的表达,从而抑制了K562/ADR细胞对阿霉素的耐药性。%Objective To investigate the effect of silenced c-FLIP mRNA level by small interfering RNA (siRNA) on adriamycin-resistance of K562/ADR cells. Methods c-FLIP siRNA and negative siRNA were transfect-ed into K562 and K562/ADR cell lines respectively, and mRNA expression of c-FLIP and multi-drug resistance gene 1 (MDR1) were detected by quantitative PCR. Cell proliferation rate was detected by MTT assay, and cell apoptosis rate was assayed by Annexin V/7-ADD double-staining method. Results Compared with negative siRNA transfection group, siRNA transfection significantly decreased c-FLIP m

  9. 蒺藜皂苷对阿霉素损伤心肌细胞的保护作用%Effect of gross saponins of Tribulus terrestris on cardiocytes impaired by adriamycin

    Institute of Scientific and Technical Information of China (English)

    张爽; 李红; 徐惠; 杨世杰

    2010-01-01

    观察蒺藜皂苷(gross saponins of Tribulus terrestris,GSTT)对阿霉素(adriamycin,ADR)诱导大鼠乳鼠心肌细胞损伤的保护作用,并初步探讨其作用机制.分离出生1~3 d大鼠心肌细胞,培养72 h后随机分为正常对照组、ADR(终浓度为2.0 mg·L~(-1))模型组和GSTT(100、30及10 mg·L~(-1))组,继续培养24 h后,应用MTT比色法检测细胞存活率,测定培养基中肌酸激酶(CK)、乳酸脱氢酶(LDH)、天门冬氨酸氨基转移酶(AST)释放量,超氧化物歧化酶(SOD)活性,丙二醛(MDA)、一氧化氮(NO)含量,并采用流式细胞仪检测细胞凋亡及应用Western blotting检测GSTT对凋亡相关蛋白caspase-3的作用.结果表明,与正常对照组比较,ADR模型组心肌细胞存活数明显减少,心肌细胞培养液中CK、LDH、AST释放量增加(P<0.01,P<0.001),同时SOD活力下降(P<0.01)而MDA、NO含量升高(P<0.001);与ADR模型组比较,GSTT(100和30 mg·L~(-1))组存活心肌细胞数增多(P<0.05,P<0.001),心肌细胞培养液中CK、LDH、AST含量明显降低,SOD活力增加、MDA和NO含量降低(P<0.05,P<0.01,P<0.001).流式细胞仪检测GSTT(100和30 mg·L~(-1))组心肌细胞凋亡数明显减少(P<0.05,P<0.01),caspase-3含量下降(P<0.05,P<0.001).GSTT对ADR损伤的心肌细胞具有保护作用,可减轻心肌细胞损伤,抑制心肌细胞凋亡,其机制与抗自由基作用有关.

  10. Intervention effect of leukotriene receptor antagonist on adriamycin-induced nephropathy rats%白三烯受体拮抗剂对多柔比星肾病大鼠的干预作用

    Institute of Scientific and Technical Information of China (English)

    刘妍; 张碧丽; 王文红; 张瑄; 王娟

    2014-01-01

    Objective To explore the effect of leukotriene receptor antagonist (LTRAs,montelukast) on serum indicators,urine indicators,renal pathology,intercellular adhesion molecule-1 (ICAM-1),nephrin and podocalyxin on renal tissue in adriamycin(ADR)-induced nephropathy(ADN) rats.Methods ADN was induced through a tail intravenons injection of ADR.The 40 healthy male Wistar rats were randomly divided into 5 groups:group A (control group),group B(ADN group),group C(prednisone-treated group),group D(montelukast-treated group) and group E (prednisone and montelukast-treated group).Twenty-four-hour urinary protein (24 h-up) and serum index were measured serially in the 4th,8th week and the values of creatinine clearance rate(Ccr) were calculated.At the end of the 8th week,all rats were sacrificed to collect kidney tissues for microscopy observation of renal pathological changes.The expression of nephrin,podocalyxin and ICAM-1 in renal tissues were detected through immunohistochemistry method.Results Compared with group A,in the 4th week,24 h-up and albumin reached the level of ADR nephropathy model.Compared with group B,in the 8th week,24 h-up,cholesterol,serum creatinine and renal pathology changes in the 3 treated groups were significantly reduced (P < 0.05),but serum total protein,albumin and Ccr significantly increased (P < 0.05),while extracellular matrix/glomerulararea and renal pathology score significantly reduced (P < 0.01),and ICAM-1 significantly decreased(P <0.01).Compared with group C and group D,expressions of nephrin and podocalyxin in group E were the highest.Besides,the curative effect of integrated treatment was better than other treatments.Conclusions Maybe through inhibition of ICAM-1,LTRAs had a protective effect on renal tissue.The integrated treatment of LTRAs with prednisone has a synergistic effect and drug effect is superior to any drug alone in ADN.%目的 通过观察白三烯受体拮抗剂(LTRAs,孟鲁司特钠)对多柔比星肾病(ADN)大

  11. 包裹阿霉素的新型载药微泡制备及体外缓释实验研究%Study on preparation of a novel adriamycin-loaded ultrasound microbubble and release characteristics in vitro

    Institute of Scientific and Technical Information of China (English)

    王希; 冉海涛; 王志刚; 宫玉萍; 董桂芳

    2013-01-01

    Objective To combine the active poly lactic co-glycolic acid (PLGA) nanosperes with adriamycin in side (ADM-NP) on the surface of ultrasound micrbubbles in covalent bonding and to prepare a novel drug-loading ultrasound micrbubble,and observe the physicochemical property.To quantify drug encapsulation efficiency and drug-loading amounts and drug-release properties in vitro and the effect of tumor imaging.Methods ADM-NP were prepared with double emulsification method,The surface carboxyl of ADM-NP was activated with carbodiimide method.Amino ultrasound microbubbles (MB-NH2) were prepared with mechanical shaking.The carboxyl of ADM-NP and the MB-NH2 could take place condensation reaction under a certain condition.Light microscope was used to observe the shape and distribution of the novel micrbubble.High performance liquid chromatography (HPLC) was used to quantify drug encapsulation efficiency and drug loading amounts.This novel microbubbles were put in 2 dialysis bag to observe the releasing properties of ADM in vitro,and one of the bag was using low frequency ultrasound irradiation for 120 s.The effect of tumor imaging using this novel microbubble was observed.Results After 48 hours,a number of ADM-NP attacted to the MB-NH2 like a gar land.Determination of entrapment efficiency and drug loading of it by HPLC weare (86.11 ± 6.76)% and (8.71 ± 0.46)%.The sustained release in vitro can last for more than 48 hours.More than 90% of ADM encapsulated in the 2 groups was sustained released for 48 hours.And the release characteristics of the 2 groups in vitro was in accord with Higuchi equation,and no difference was observed in the 2 groups (P >0.05).The tumor showed typical enhancement pattems of "quick wash-in and quick wash-out".Conclusions To combine the nanospheres to the surface of microbubbles with covalent bonding,it could prepare a novel efficient drug-loading microbubbles for a original technique of ultrasound-targeted microbubble destruction

  12. 口虾蛄乙酸乙酯提取物联合阿霉素或顺铂对人肝癌HepG2细胞的增殖抑制效应研究%Inhibitory effects on proliferation of human hepatoma line HepG2 by ethyl acetate extract of squilla oratoria in combination with adriamycin or cisplatin

    Institute of Scientific and Technical Information of China (English)

    邵松军; 李明勇; 张湘宁; 黄培春

    2013-01-01

    目的研究海洋生物口虾蛄乙酸乙酯提取物联合阿霉素或顺铂对人肝癌 HepG2细胞株的增殖抑制效应,并定量分析其协同、相加或拮抗的作用。  方法不同浓度的口虾蛄乙酸乙酯提取物联合阿霉素或顺铂处理肝癌 HepG2细胞株24 h,用 MTT 法测定细胞的生长抑制作用,并用中效原理法、金氏修正公式分析药物的联合作用。  结果口虾蛄乙酸乙酯提取物、阿霉素、顺铂单用或联合用药作用于肝癌 HepG2细胞株,均能抑制细胞的增殖,呈现量-效依赖性。口虾蛄乙酸乙酯提取物与传统化疗药物的联合用药增加了传统化疗药物对肝癌细胞的毒性作用,呈现出低浓度拮抗,而高浓度协同的作用。  结论海洋生物口虾蛄乙酸乙酯提取物作为一类新型、天然的抗肿瘤药物,可有效地抑制肝癌 HepG2细胞的增殖。%Objective To study inhibitory effects on proliferation of human hepatoma line HepG2 by ethyl acetate extract of squilla oratoria (ESO) in combination with routine anticancer chemotherapeutic agents adriamycin or cisplation, and qunatatively analyze the additive or antagonist effects between ESO and the two drugs. Methods The HepG2 cells were treated with either ESO, adriamycin or cisplatin alone, or ESO/adriamycin, ESO/cisplatin in combination for 24 h. The growth inhibition was assayed with MTT method, and the synergistic effect of different drugs was evaluated with Median-effect principle, the Revised Jin’s formula. Results The three drugs all exerted inhibitory effect on the growth of HepG2 cells in a dose-dependent manner, and the combination also decreased the proliferation of the cells. The combination with different chemotherapy agents increased cytotoxic effects on cells, and low concentration showed a synergistic effect, but the high concentrations demonstrated the antagonistic effect. Conclusions Marine squilla oratoria as a new class of natural

  13. Expression of nephrin and podocalyxin in rats with adriamycin-induced nephrosis and intervention effect of prednisone%阿霉素肾病大鼠nephrin及podocalyxin蛋白表达及泼尼松干预作用的探讨

    Institute of Scientific and Technical Information of China (English)

    胡小云; 张碧丽

    2011-01-01

    Objective To investigate the expression of nephrin and podocalyxin in rat* with adriamycin-indueed ne-phrosis ( AND) and the intervention effect of prednisone. Methods Twenty-four male Wistar rats were randomly divided into three groups, which were AND group, prednisone group, control group. Serum cholesterol, albumin ( Alb) , and the 24-hour urine protein (24hUP) were measured serially in the 0, 4th, and 8th week. Kats were sacrificed to collect kidney tissue for pathological morphology observation in the end of study (the 8th week). Extracellular matrix/glumerular area ratio ( ECM/GA) and renal pathology points were determined. The expression of nephrin and podoealyxin in glomerulus werp examined by means of inimunohistm-hemistry. Results In the 4th week, 24hUP and cholesterol were significantly higher in AND group than those in control group respectively ( P < 0.05 ) , while Alb was significantly lower ( P < 0. 01 ). In the 8th week, compared with AND group, in prednisone group, 24hUP, cholesterol, ECM/GA, and renal pathology points were significantly lower ( P <0.01 ) , while Alb and the expression of nephrin and podocalyxin were significantly higher (P <0.0I ). The expression of nephrin and podocalyxin in AND group were negatively correlated with 24hUP, cholesterol, ECM/GA and glomerular pathology point, and positively correlated with Alb. The expression of nephrin was positively correlated with that of podocalyxin. Conclusions Nephrin and podocalyxin are closely related to the progression of proteinuri-a. The mechanism of the prednisone alleviating proteinuria and kidney pathological damage may be correlated to the up-reg-ulation of the expression of nephrin and podocalyxin.%目的 探讨阿霉素肾病( ADN)大鼠肾组织nephrin及polxalyxin蛋白表达及泼尼松的干预作用.方法 24只雄性Wistar大鼠随机分成ADN组、泼尼松组、对照组.于0、4、8 周测定大鼠24 h尿蛋白(24hUP)、血清胆固醇(Cho)及白蛋白(Alb) 实验8周取

  14. Low milli-ampere electrochemical therapy reverses multidrug resistance and induces apoptosis on breast cancer MCF-7/adriamycin cell line%低毫安电化学疗法诱导人乳腺癌耐药株MCF-7/阿霉素细胞凋亡及逆转多药耐药的研究

    Institute of Scientific and Technical Information of China (English)

    周炳刚; 沈义军; 魏昌晟; 杨涛; 张智; 余生林; 余建军

    2015-01-01

    Objective To explore the mechanism of reversing mutidrug reisistance and inducing apoptosis on human breast cancer MCF-7/adriamycin (ADR) cell line by electrochemical therapy (ECT).Methods Methyl thiazol tetrazolium (MTT) assay,Annexin V assay and confocal laser scanning microscope were used to measure the inhibitory rate an the change of apoptosis.Fluorospectrophotometry was usd to measure the change of the concertration of ADR in the cells.Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting were used to evaluate the mRNA and protein expression levels of multidrug resistance 1 gene (MDR1),phosphatase and tensin homologue deleted on chromosometen (PTEN),protein kinase B (Akt) and Caspase-3 in MCF-7/ADR cells.Results ECT could inhibit growth obviously of the MCF-7/ADR cells,and the apoptosis rate of cells was increased obviously in the treated group as compared with that in the control group (P < 0.05).5 C ECT could obviously increase the intracellular concentration of ADR 4.61 times.With the increases in the power of electricity,the expression of PTEN and cleaved Caspase-3 was obviously higher than in the control group,but the protein expression of Permeability glycoprotein (P-gp) (0.293 ± 0.013),and p-Akt (0.397 ± 0.020) in 5 C ECT group (P < 0.01) was reduced gradually with the increases in the power electricity.Conclusion ECT can inhibit the proliferation of MCF-7/ADR cells,induce apoptosis and reverse MDR probably by inhibiting PI3K/Akt signal pathway.%目的 探讨低毫安电化学疗法(ECT)对人乳腺癌耐药株MCF-7/阿霉素(ADR)细胞诱导凋亡及逆转多药耐药(MDR)的作用机制.方法 电化学处理细胞后继续培养6h和24h,用噻唑蓝(MTT)法、膜联蛋白V(Annexin V)染色、激光共聚焦显微镜观察ECT对肿瘤细胞的生长抑制、凋亡变化;荧光分光光度法检测细胞内ADR的浓度;实时定量聚合酶链反应(Real-time PCR)法、Western blot法检测多药耐药基因(MDR1

  15. Effects of x-irradiation and Adriamycin on proliferating and nonproliferating hair coat of the mouse

    International Nuclear Information System (INIS)

    Dose-response curves for proliferating, nonproliferating, and nonproliferating hair coat stimulated 24 hours after treatment show similar D/sub O/ of 135 rad and a D/sub q/ of 500, 900, and 1400 rad respectively. Using a priming dose of 650 rad x-rays, a drug-dose-response curve was established in the proliferating hair coat. Drug-dose-response curve was established for the nonproliferating, stimulated coat with priming doses of 1200 and 1400 rad. No drug effect could be seen in the nonproliferating hair coat left unstimulated. Cyclic interaction between drug and irradiation was found in the proliferating hair coat

  16. Electrochemical behavior of adriamycin at a cobalt ion implantation modified electrode

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    With Co/GCE in 0.005 mol Tris/L/0.05 mol/L NaCl solution (pH 7.1), a sensitive reductive peak of adriamgcin (ADM) was obtained by the linear scan voltammetry.The peak potential is -0.62 V (vs. SCE). The peak current is proportional to the concentration of ADM. The electrochemical behavior of the system was studied by the linear-sweep and cyclic voltammetry. The experiments showed that the reduction at Co/GCE is a quasi-reversible process with adsorption. According to Laviron's theory, the electrode reaction cate constant ko and the electron transfer coefficient a are determined to be 2.15 s-1 and 0.62, respectively. The composition of the surface, valence state of elements and depth distribution of elements on the surfaces of Co/GCE were determined by the X-ray photoelectron spectroscopy and Auger electron spectroscopy. The experiments showed that Co was surely implanted into the surface of GCE. The implanted Co element in the form of Co-C catalyzed the reduction of ADM.

  17. Computerized cyclic voltammetric detection after HPLC of the antineoplastic agents etoposide, teniposide, adriamycin and its metabolite adriamycinol in urine samples

    OpenAIRE

    Ploegmakers, H. H. J. L.; Moritz, P. A.; Toll, P. J. M. M.; Oort, W.J. van

    1989-01-01

    A computerized electrochemical detection system for application after HPLC, provided with a cyclic voltammetric oxidative and reductive module, is described for the on-line qualitative determination of electroactive antineoplastic agents and metabolites in urine samples, collected from cancer patients, following intravenous administration. The application of two cyclic voltammetric detection modes provides an insight into both oxidative and reductive electrode reactions of compounds, passing ...

  18. Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

    International Nuclear Information System (INIS)

    We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52±15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m2 or higher were assigned to the high dose group and those given doses under 300 mg/m2 to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3±218.2 mg/m2. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m2 appeared to be the borderline dose beyond which there were significant cardiac functional disorders. (author)

  19. The effect for metastasis of urinary tract cancer by combination therapy with adriamycin and low dose radiation

    International Nuclear Information System (INIS)

    Thee were 12 cases (men 11 and 1 woman) with metastasis of urinary tract cancer. Average age was 65.3 years. Primary tumors were 7 bladder cancers, 3 pelvico-ureter cancers and 2 renal cell carcinomas. Treatment was mainly intravenous administration of 100 mg ADM and low dose of local radiation (2000 rad). Effective rate was 85.7% for metastasis of transitional cell carcinoma, but effective rate was 0% by treatment of administration of 30 mg ADM and local low dose radiation (2000 rad). No effect to metastasis of renal cell carcinoma was observed. (author)

  20. Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu [Tokyo Medical Coll. (Japan)

    2001-05-01

    We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52{+-}15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m{sup 2} or higher were assigned to the high dose group and those given doses under 300 mg/m{sup 2} to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3{+-}218.2 mg/m{sup 2}. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m{sup 2} appeared to be the borderline dose beyond which there were significant cardiac functional disorders. (author)

  1. Radioimmunoassay and systolic time interval as control parameters for prophylactic and early diagnosis of side-effects of cytostatic therapeutic treatment using adriamycin and methotrexate

    International Nuclear Information System (INIS)

    It is possible, with the aid of a newly developed radioimmunoassay to detect the cytostatic methotrexate in the serum of patients up to concentrations of 1.1x10-8 mol/l. This makes a harmless highdose therapy possible. (orig./MG)

  2. Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

    OpenAIRE

    Caner Isbir

    2016-01-01

    Aim: Scarcity of the interstitial cells of Cajal (ICC) is related to motility disorders. In the study, we aimed to evaluate the number and density of ICCs in the fetal rat esophagus in the adriamycin - esophageal atresia (EA) model. Material and Method: Rat fetuses were divided into three groups as a control, adriamycin group without EA and adriamycin group with EA. Four doses of adriamycin, 2 mg/kg each, were injected intraperitoneally to the adriamycin group rats between on 6 and 9 days of ...

  3. 流式细胞术分析五味子乙素促进阿霉素内化的实验研究%Analyzing the promotion of internatization of adriamycin by schisapoun B through flow cytometry

    Institute of Scientific and Technical Information of China (English)

    孙德一; 张铎; 王海杰; 李妍

    2012-01-01

    [目的]建立流式细胞术分析肿瘤细胞内阿霉素分布的方法,并研究低浓度五味子乙素对K562细胞内化阿霉素的影响.[方法]体外培养猪内皮细胞(pEC),以20 μ mol/L阿霉素处理2、4和6小时;或加入不同浓度阿霉素(0、10、20、40、80和100μmol/L)处理4小时.培养K562细胞,以5μmol/L阿霉素处理2、4和6小时;或加入不同浓度阿霉素(0、2.5、5,10和20μmol/L)处理4小时.采用不同浓度(0、25、50和100 μ mol/L)五味子乙素(Sch B)与阿霉素联合处理K562细胞4小时.收集细胞,采用流式细胞术分析阿霉素的特异荧光.[结果]固定浓度处理pEC (20 μ mol/L)和K562(5 μ mol/L)后检测,发现细胞内荧光强度随时间延长而增加,两种细胞4小时组荧光强度分别达到6小时组的96.93%和95.23%/.在直方图上,阴性和阳性细胞群界限分明.阿霉素(2 5、5和10 μ mol/L)单独处理细胞的荧光强度分别为26.78士3.34、64.70士6.24和118.35±9.67;添加25μmol/L Sch B 实验后荧光强度增加到43.45±4.25、103.74±7.36和146.69土8.32,Sch B 显著增加了K562细胞内阿霉素的分布(p<0.05).[结论]建立的方案可快速测定细胞内的阿霉素分布;低浓度Sch B促进肿瘤细胞内化阿霉素.

  4. CHOP方案对儿童非何杰金恶性淋巴瘤治疗作用的观察%Effect of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) regimen on non-Hodgkin's Lymphoma of children and adolescents

    Institute of Scientific and Technical Information of China (English)

    高亮; 南克俊; 张琴阳; 张志明; 闫小利

    2002-01-01

    目的:观察CHOP方案对儿童不同细胞来源中高度非何杰金恶性淋巴瘤(NHL)的疗效及不良反应.方法:CHOP方案(CTX750mg/m2静注d1,VCR1.4mg/m2静注d1、8,ADM40mg/m2静注d1,PDN 100mg/m2口服d1~5,21d重复,共用2周期)治疗病理学证实的儿童中高度非何杰金恶性淋巴瘤25例,观察其疗效和不良反应.结果:25例病人完全缓解率40%,总有效率92%,T细胞型总有效率75%,B细胞型总有效率100%,初治病人有效率100%,复治病人有效率71%,主要不良反应为骨髓抑制,Ⅲ~Ⅳ度白细胞减少占24%,血小板减少程度较轻.结论:CHOP化疗方案是治疗儿童中高度非何杰金恶性淋巴瘤安全有效的方案,对B细胞来源儿童NHL疗效明显优于T细胞来源者.

  5. Learning about Lymphoma: Glossary of Terms

    Science.gov (United States)

    ... fluorouracil (5-FU), methotrexate, pentostatin, piritrexim, and trimetrexate. antineoplastic antibiotics: A group of chemotherapy drugs including cordycepin and the anthracyclines doxorubicin (Adriamycin, AD ...

  6. Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

    Directory of Open Access Journals (Sweden)

    Caner Isbir

    2016-04-01

    Full Text Available Aim: Scarcity of the interstitial cells of Cajal (ICC is related to motility disorders. In the study, we aimed to evaluate the number and density of ICCs in the fetal rat esophagus in the adriamycin - esophageal atresia (EA model. Material and Method: Rat fetuses were divided into three groups as a control, adriamycin group without EA and adriamycin group with EA. Four doses of adriamycin, 2 mg/kg each, were injected intraperitoneally to the adriamycin group rats between on 6 and 9 days of gestation. The presence of ICCs in the esophagus of the rat fetuses was determined by using an immunohistochemistry technique (c-kit, CD117. The average numbers of ICCs were calculated with microscopic evaluation by using a visual scoring system (range1 to 3. Results: Seven fetuses were included in each group. The ICCs score 3 distributions of fetuses were 5 (72% fetuses in the control group, 3 (43% fetuses in the adriamycin group without EA, 1 (14% fetus in the adriamycin group with EA. It have been found that there was a marked reduction of ICCs distribution in the adriamycin group with EA compared to control group (p 0.05. Discussion: ICCs density was significantly decreased in the rat fetuses with EA compared to the fetuses without EA. These findings support the idea that ICCs density may be congenitally abnormal in EA. This may be led to dismotility seen in the operated esophagus due to EA.

  7. NCBI nr-aa BLAST: CBRC-GGOR-01-0881 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGOR-01-0881 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  8. NCBI nr-aa BLAST: CBRC-STRI-01-2054 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2054 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  9. NCBI nr-aa BLAST: CBRC-MMUR-01-1003 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-1003 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  10. NCBI nr-aa BLAST: CBRC-PCAP-01-0448 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PCAP-01-0448 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  11. NCBI nr-aa BLAST: CBRC-TTRU-01-0187 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-0187 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  12. NCBI nr-aa BLAST: CBRC-PHAM-01-1129 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-1129 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  13. NCBI nr-aa BLAST: CBRC-PVAM-01-0604 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PVAM-01-0604 ref|NP_598498.1| LanC (bacterial lantibiotic synthetase component C)-like 2 [M ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein dbj|BAA96801.1| testis-specific adriamycin ... sensitivity ... protein [Mus musculus] gb|AAH16072.1| Lancl2 prote ...

  14. 3-溴丙酮酸联合阿霉素对乳腺癌细胞增殖及凋亡的影响%Effect of 3-bromopyruvate combined with adriamycin on proliferation and apoptosis of human breast carcinoma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    刘哲; 张媛媛; 张倩文; 钟浩; 孙小锦; 蒋琛琛; 蒋志文; 刘浩

    2014-01-01

    目的:研究3-溴丙酮酸(3-BrPA)联合阿霉素(ADM)对乳腺癌细胞MDA-MB-231增殖及凋亡的影响.方法:采用3-BrPA 80、160、320 μmol/L作用于MDA-MB-231乳腺癌细胞18 h后,测定其对细胞内ATP的影响;分别用3-BrPA 10、20、40、80、160 μmol/L和ADM 0.75、1.5、3、6、12 μmol/L,以及3-BrPA 80 μmol/L与ADM 0.75、1.5、3、6、12 μmol/L合用作用于MDA-MB-231乳腺癌细胞24、48和72 h后,MTT法检测乳腺癌细胞MDA-MB-231增殖情况;3-BrPA 80 μmol/L组、ADM 0.75 μmol/L组以及3-BrPA 80 μmol/L与ADM 0.75 μmol/L合用组作用于乳腺癌细胞MDA-Mb-231 24 h后,利用碘化丙啶染色,流式细胞仪检测其诱导乳腺癌细胞凋亡的影响;采用3-BrPA 16 μmol/L、ADM 0.2 μmol/L以及3-BrPA 16 μmol/L与ADM 0.2 μmol/L合用作用于乳腺癌细胞MDA-MB-231,5 d后观察对集落克隆形成的影响.结果:3-BrPA对乳腺癌细胞MDA-MB-231 ATP的生成有抑制作用;3-BrPA联合ADM后可明显增强ADM的细胞毒性作用;3-BrPA 80 μmol/L与ADM 0.75 μmol/L合用组诱导乳腺癌细胞MDA-MB-231 24 h凋亡率为39.6%,均显著高于对照组、3-BrPA单用组和ADM单用组(P<0.01);3-BrPA增强ADM对乳腺癌细胞MDA-MB-231集落克隆形成的抑制作用.结论:3-BrPA可以增强ADM对乳腺癌细胞MDA-MB-231增殖的抑制作用以及增强ADM诱导乳腺癌细胞凋亡的作用.

  15. Analysis of Inhibitory Effect of Adriamycin Combined with Sola Feeney on Hepatocellular Carcinoma Cell Line HepG2%研究与分析阿霉素联合索拉菲尼对肝癌细胞株HepG2的抑制作用及机制

    Institute of Scientific and Technical Information of China (English)

    王燕燕

    2015-01-01

    Objective Research and Analysis of hepatoma cel lines by doxorubicin treated with sorafenib and mechanism of inhibition of HepG2.Methods According to drug use into sorafenib group (Group A),doxorubicin group (Group B),doxorubicin combined with sorafenib group (Group C);and acts on the liver cel line HepG2 cel s,respectively.Analysis and comparison of the three groups and inhibition of cel proliferation and apoptosis and so on.Results Three groups can ef ectively inhibit the proliferation of HepG2 cel s in a dose-dependent manner;but Group C has a synergistic ef ect( <0.05).A,B can make HepG2 cel cycle ar est in G0-G1 phase;but Group C G0/G1 phase of the cel ratio was significantly lower than the A and B groups;was significantly higher than that of B and S groups ( <0.05).Three groups can induce apoptosis in HepG2 cel s,but Group C is more significant ( <0.05);B can ef ectively inhibit Survivin mRNA expression in HepG2 cel apoptosis induced cel s. Conclusion Doxorubicin combined with sorafenib for hepatocel ular carcinoma cel line HepG2 has good synergistic ef ect,but can also accelerate cel proliferation,thereby restrain the growth ef ect of tumor cel s.Therefore,further clinical studies to bet er provide reference for clinical treatment of liver cancer,thereby improving patient outcomes.%目的:研究与分析肝癌细胞株经阿霉素与索拉菲尼处理后对HepG2的抑制作用及机制。方法按照药物使用情况分为索拉菲尼组(甲组)、阿霉素组(乙组)、阿霉素联合索拉菲尼组(丙组);并分别作用于肝细胞株HepG2细胞。并分析与比较三组细胞增殖抑制及细胞凋亡等情况。结果三组均可有效抑制HepG2细胞增殖,且存在剂量依赖性;但丙组具有协同效应(<0.05)。甲、乙组均可使HepG2细胞周期停滞于G0-G1期;但丙组G0/G1期细胞比率明显低于甲乙两组;且S期明显高于甲乙两组(P<0.05)。三组均可诱导HepG2细胞凋亡,但丙组更加显著(<0.05);乙组可有效抑制HepG2细胞Survivin mRNA表达诱导细胞的凋亡。结论阿霉素联合索拉菲尼对肝癌细胞株HepG2具有较好协同效果,同时还可加速细胞增殖抑制,从而起到抑制肿瘤细胞生长效果。因此,临床可进一步研究,以更好地为肝癌临床治疗提供参考依据,从而改善患者预后。

  16. 核仁素表达下调对阿霉素所致乳腺癌细胞增殖抑制和凋亡的影响%Effect of down-regulation of nucleolin on adriamycin-induced apoptosis and inhibition of proliferation in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    田晓彩; 刘先领; 胡春宏

    2010-01-01

    @@ 乳腺癌是女性最常见的恶性肿瘤,我国的乳腺癌发病率呈急剧上升的趋势.核仁素是真核生物核仁中最主要的一种磷酸蛋白质,具有多种生物学功能,包括调控核糖体的合成与成熟,调控细胞的增殖、生长、胚胎发生、胞质分裂、染色体复制和核仁发生等过程.我们探讨了下调核仁素表达对乳腺癌细胞增殖抑制和凋亡的影响,现将结果报告如下.

  17. NCBI nr-aa BLAST: CBRC-PVAM-01-0604 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PVAM-01-0604 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  18. NCBI nr-aa BLAST: CBRC-MLUC-01-0117 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0117 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  19. NCBI nr-aa BLAST: CBRC-MDOM-06-0167 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-06-0167 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  20. NCBI nr-aa BLAST: CBRC-STRI-01-2054 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2054 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  1. NCBI nr-aa BLAST: CBRC-MMUR-01-1003 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-1003 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  2. NCBI nr-aa BLAST: CBRC-PHAM-01-1129 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-1129 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  3. NCBI nr-aa BLAST: CBRC-PCAP-01-0448 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PCAP-01-0448 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  4. NCBI nr-aa BLAST: CBRC-GGOR-01-0881 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGOR-01-0881 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  5. NCBI nr-aa BLAST: CBRC-TSYR-01-0555 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TSYR-01-0555 ref|NP_061167.1| LanC lantibiotic synthetase component C-like 2 [Homo sapiens] ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  6. Gene : CBRC-GGOR-01-0881 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGOR-01-0881 Novel UN A UNKNOWN LANC2_HUMAN 1e-167 68% ref|NP_061167.1| LanC lantibiotic sy ... rotein 2; AltName: Full=Testis-specific adriamycin sensitivity ... protein gb|AAK83286.1|AF353942_1 lantibiotic synth ... apiens] dbj|BAA96800.1| testis-specific adriamycin sensitivity ... protein [Homo sapiens] emb|CAC21715.1| LanC-like p ...

  7. Systemic chemotherapy of advanced head and neck malignancies.

    Science.gov (United States)

    Dowell, K E; Armstrong, D M; Aust, J B; Cruz, A B

    1975-04-01

    Several Phase II chemotherapy protocols were evaluated in patients with advanced malignancies; 158 were evaluable head and neck cases. The protocols were as follows: five-drug combination (COMFP), four-drug (COMF), (CCNU, Adriamycin, DTIC, and cytosine arabinoside. Insufficient numbers and data were received to adequately evaluate Yoshi 864, 5 Azacytidine, porfiromycin, BCNU, and Azaserine. Significant responses to therapy were noted in the four and five-drug combinations in which 30-44% of the patients had 50% or greater regression, with an average duration of 2.2 months. Adriamycin and CCNU demonstrated lesser antitumor effects, while DTIC and cytosine arabinoside did not demonstrate significant antitumor activity in the head and neck areas. Usual toxicity consisted largely of nausea and vomiting, leukopenia, and thrombocytopenia. Alopecia was not pronouced in Adriamycin-treated patients. It appears that combination chemotherapy had a higher response rate compared to single agents used in the different cooperative protocols. PMID:1116105

  8. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

    Directory of Open Access Journals (Sweden)

    Benitez-Bribiesca Luis

    2006-08-01

    Full Text Available Abstract Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype.

  9. EBV-positive immunodeficiency lymphoma after alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke C.; Coenen, Jules L.; Boers, James E.; van Imhoff, Gustaaf W.; Rosati, Stefano

    2008-01-01

    Chemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials; will incorporate this scheme. As part of an ongoing phase 2 trial in which we re

  10. Phase II Study of Paclitaxel in Patients With Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Robert Benjamin

    1997-01-01

    Full Text Available Purpose. Patients with soft tissue sarcoma (STS who have previously received standard chemotherapy including adriamycin (doxorubicin, ifosfamide, cyclophosphamide and DTIC (dacarbazine have very limited therapeutic options. It is important to identify new drugs with some activity in this disease and we therefore undertook this trial to determine the antitumor activity of paclitaxel (Taxol.

  11. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Autrup, Judith; Hokland, Peter; Pedersen, Lars;

    2002-01-01

    The objective of the study was to investigate the effect of genetic polymorphisms in glutathione S-transferases (GST) on the survival of acute myeloid leukaemia patients receiving adriamycin induction therapy. A total of 89 patients were included in the study. Patients who carried at least one GSTM...

  12. Preformulation Studies on Piperlongumine

    OpenAIRE

    Alhassan Aodah; Aaron Pavlik; Kelly Karlage; Myrdal, Paul B.

    2016-01-01

    Piperlongumine is a natural alkaloid extracted from piper plants which has been used traditionally for the treatment of certain diseases. This compound shows interesting in vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties for this compound have not been well characterized. In this research, preformulati...

  13. Isolated Pelvic Hyperthermochemotherapeutic Perfusion -An Experimental Study on Isolating Efficacy

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Hyperthermochemotherapeutic perfusion model through isolated pelvic vessels was developed to evaluate the leakage of hyperthermia and drugs (such as adriamycin) from the isolated pelvic circulation to systemic circulation and its associated side/toxic effects. The isolated pelvic circulation was perfused through a femoral artery catheter with hyperthermic (48 ℃ to 55 ℃) adriamycin solution (50 μg/ml) for 30 min. The efflux was drained through a femoral vein catheter. And the pelvic temperature was kept at the level of 43±0.5 ℃. The temperature of pelvic circulation was kept at 4 ℃ to 5 ℃ greater than the systemic/core temperature. The adriamycin concentration of pelvic efflux was 12 to 46 folds of that of systemic serum. The difference between them was very significant (P<0.001). As the perfusion pressure was increased, which kept lower than the mean systemic artery pressure, the leakage of the adriamycin from the isolated pelvic circulation to systemic circulation was increased, but there was no significant difference between them (P>0.05). During isolated perfusion, the systemic blood dynamics remained stable and there were no organic injuries on the important organs. It was suggested that the isolating efficacy of the modality of isolated pelvic hyperthermochemotherapeutic perfusion through vessels was rather high. The hyperthermia and drugs could be effectively limited in the isolated pelvic region with minor side effects on the systemic circulation and important organs.

  14. INVITRO AND INVIVO MODULATION OF MULTIDRUG RESISTANCE WITH AMIODARONE

    NARCIS (Netherlands)

    VANDERGRAAF, WTA; DEVRIES, EGE; UGES, DRA; NANNINGA, AG; MEIJER, C; VELLENGA, E; MULDER, POM; MULDER, NH

    1991-01-01

    The modulating effect on drug resistance of amiodarone (AM) and its metabolite desethylamiodarone (DEA) was studied in a P-glycoprotein-positive human colon carcinoma cell line COLO 320, and a human small-cell lung carcinoma cell line GLC4 and its adriamycin (Adr)-resistant subline GLC4-Adr (both P-

  15. Ototoxicity following Vinblastine chemotherapy in a patient of Hodgkin′s Lymphoma

    Directory of Open Access Journals (Sweden)

    Raj Kumar Nirban

    2015-01-01

    Full Text Available Sudden hearing loss is a well-known complication of certain chemotherapeutic agents. However, vinblastine has seldom been implicated causing ototoxicity. We report a case of sudden bilateral hearing loss in a 36-year-old male patient of Mixed cellularity Hodgkin′s lymphoma following standard adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy.

  16. Optical coherence tomography (OCT) of a murine model of chronic kidney disease

    Science.gov (United States)

    Wang, Hsing-Wen; Guo, Hengchang; Andrews, Peter M.; Anderson, Erik; Chen, Y.

    2015-03-01

    Chronic Kidney Disease (CKD) is characterized by a progressive loss in renal function over time. Pathology can provide valuable insights into the progression of CKD by analyzing the status of glomeruli and the uriniferous tubules over time. Optical coherence tomography (OCT) is a new procedure that can analyze the microscopic structure of the kidney in a non-invasive manner. This is especially important because there are significant artifacts associated with excision biopsies and immersion fixation procedures. Recently, we have shown that OCT can provide real time images of kidney microstructure and Doppler OCT (DOCT) can image glomerular renal blood flow in vivo without administrating exogenous contrast agents. In this study, we used OCT to evaluate CKD in a model induced by intravenous Adriamycin injection into Munich-Wistar rats. We evaluated tubular density and tubular diameter from OCT images at several post- Adriamycin induction time points and compared them with conventional light microscopic histological imaging. Proteinurea and serum creatinine were used as physiological markers of the extent of CKD. Preliminary OCT results revealed changes in tubular density due to tubular necrosis and interstitial fibrosis within the first 4 weeks following Adriamycin injection. From week 4 to 8 after Adriamycin induction, changes in tubular density and diameter occurred due to both tubular loss and tubular dilation. The results suggest OCT can provide additional information about kidney histopathology in CKD. DOCT revealed reduced blood flow in some glomeruli probably as a consequence of focal glomerularsclerosis.

  17. Blocking CHK1 Expression Induces Apoptosis and Abrogates the G2 Checkpoint Mechanism

    Directory of Open Access Journals (Sweden)

    Yan Luo

    2001-01-01

    Full Text Available Checkpoint kinase 1 (Chki is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chki expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chki inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chki is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

  18. Study of multidrug resistance and radioresistance

    International Nuclear Information System (INIS)

    We investigated the mechanism of 5-FU, adriamycin, radiation resistance in Korean gastric cancer cells. First we investigated the relation between Rb and multidrug resistance. Rb stable transfectants exhibited 5- to 10- fold more resistance to adriamycin than the control cells. These Rb transfectants showed increased MDR1 expression. We also investigated up-regulation in radiation-resistant tumor tissues. HSP27, MRP-8, GST, and NKEF-B were up-regulated in radiation resistant tumor. Expression of NKEF-B was also increased by radiation exposure in Head and Neck cells. These results demonstrated that NKEF-B is a stress response protein and it may have an important role in radiation resistance

  19. Study of multidrug resistance and radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yoon Koo; Yoo, Young Do

    1999-04-01

    We investigated the mechanism of 5-FU, adriamycin, radiation resistance in Korean gastric cancer cells. First we investigated the relation between Rb and multidrug resistance. Rb stable transfectants exhibited 5- to 10- fold more resistance to adriamycin than the control cells. These Rb transfectants showed increased MDR1 expression. We also investigated up-regulation in radiation-resistant tumor tissues. HSP27, MRP-8, GST, and NKEF-B were up-regulated in radiation resistant tumor. Expression of NKEF-B was also increased by radiation exposure in Head and Neck cells. These results demonstrated that NKEF-B is a stress response protein and it may have an important role in radiation resistance.

  20. Clinical study on external carotid artery infusion (trans-femoral) treatment of recurrent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect and safety of external carotid artery infusion treatment of recurrent nasopharyngeal carcinoma (NPC). Methods: 20 cases of recurrent NPC (13 male and 7 female, age 36-65 years, mean 50 years) diagnosed by clinical examination (including nasopharyngoscope), serology (VCA-IgA) and imaging (CT, MR) and treated by external carotid artery infusion (trans-femoral) with adriamycin (or epi-adriamycin), cisplatin (or carboplatin), Pingyangmycin and 5-Fluorouracil. Results: Of all the patients, 8 cases (40%) had a complete response (CR), 7 cases (35%) had a partial response (PR). The overall response rate (CR + PR) was 75%. Cumulative survival rates at 1, 3 years were 90% (18/20), 50%(10/20) respectively. No severe side-effects and complications found. Conclusion: External carotid artery infusion (trans-femoral) should be effective and safe in the treatment of recurrent NPC

  1. Delivery of anticancer drugs and antibodies into cells using ultrasound

    Science.gov (United States)

    Wu, Junru; Pepe, Jason; Rincon, Mercedes

    2005-04-01

    It has been shown experimentally in cell suspensions that pulsed ultrasound (2.0 MHz) could be used to deliver an anti-cancer drug (Adriamycin hydrochloride) into Jurkat lymphocytes and antibodies (goat anti rabbit IgG and anti mouse IgD) into human peripheral blood mononuclear (PBMC) cells and Jurkat lymphocytes assisted by encapsulated microbubbles (Optison). When Adriamycin hydrochloride (ADR) was delivered, the delivery efficiency reached 4.80% and control baseline (no ultrasound and no ADR) was 0.17%. When anti-rabbit IgD was delivered, the efficiencies were 34.90% (control baseline was 1.33%) and 32.50% (control baseline was 1.66%) respectively for Jurkat cells and PBMC. When goat anti rabbit IgG was delivered, the efficiencies were 78.60% (control baseline was 1.60%) and 57.50% (control baseline was 11.30%) respectively for Jurkat cells and PBMC.

  2. Second look laparotomy in the management of epithelial cell carcinoma of the ovary.

    OpenAIRE

    Mead, G. M.; Williams, C. J.; MacBeth, F. R.; Boyd, I. E.; Whitehouse, J M

    1984-01-01

    Case histories from 20 patients undergoing postchemotherapy "second look" laparotomy for metastatic epithelial cell carcinoma of the ovary were reviewed in an attempt to evaluate the usefulness of this procedure and its likely impact on patient survival. The patient population comprised 18 patients treated with a combination of cisplatin, adriamycin and cyclophosphamide (PACe) and 2 patients treated with chlorambucil. The findings at second look were often predictable, and related to the adeq...

  3. Hodgkin's disease with leptomeningeal involvement. Report of a case with long survival

    International Nuclear Information System (INIS)

    A 30-year-old white man with Stage IV B Hodgkin's disease, mixed cellularity type, developed leptomeningeal involvement shortly after relapsing on nitrogen mustard, Oncovin (vincristine), procarbazine, and prednisone (MOPP), and while receiving Adriamycin (doxorubicin), bleomycin, Velban (vinblastine), and dacarbazine (ABVD). Whole brain irradiation and intrathecal methotrexate were successfully incorporated into his treatment program. The patient has now been in complete remission for more than 40 months. A review of this rare complication of Hodgkin's disease is presented

  4. Prevention of chemotherapy-induced alopecia in rodent models

    OpenAIRE

    Jimenez, Joaquin J.; Roberts, Stephen M; Mejia, Jessica; Mauro, Lucia M.; Munson, John W.; Elgart, George W; Connelly, Elizabeth Alvarez; Chen, Qingbin; Zou, Jiangying; Goldenberg, Carlos; Voellmy, Richard

    2008-01-01

    Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy....

  5. Reversible posterior leukoencephalopathy after combination chemotherapy

    International Nuclear Information System (INIS)

    We describe a young woman with Burkitt's lymphoma, treated with intravenous adriamycine and cyclophosphamide and intrathecal cytarabine. She developed a reversible posterior leukoencephalopathy syndrome (RPLS) with typical MRI findings. Diffusion-weighted images during the first days after the onset of symptoms predicted a small irreversible lesion in the frontal lobe, verified on T2-weighted images 1 month later. The patient showed full recovery after high-dose steroid treatment. (orig.)

  6. ESR of copper and iron complexes with antitumor and cytotoxic properties.

    OpenAIRE

    Antholine, W E; Kalyanaraman, B.; Petering, D H

    1985-01-01

    The relatively few iron and copper metal complexes which have been examined in cells and tissues for their redox properties, radical generation properties, and antitumor activity are discussed for studies which utilized electron spin resonance spectroscopy (ESR). A common property of a number of metal complexes, which include bleomycin, adriamycin, and thiosemicarbazones described in this review, is that they are readily reduced by thiol compounds and oxidized by oxygen or reduced species of ...

  7. Topoisomerase inhibitors can selectively interfere with different stages of simian virus 40 DNA replication.

    OpenAIRE

    Snapka, R M

    1986-01-01

    I have found that antineoplastic drugs which are known to be inhibitors of mammalian DNA topoisomerases have pronounced and selective effects on simian virus 40 DNA replication. Ellipticine, 4'-(9-acridinylamino)methanesulfon-m-aniside, and Adriamycin blocked decatenation of newly replicated simian virus 40 daughter chromosomes in vivo. The arrested decatenation intermediates produced by these drugs contained single-strand DNA breaks. Ellipticine in particular produced these catenated dimers ...

  8. Propofol extravasation in a breast cancer patient.

    Science.gov (United States)

    Huijbers, E J M; Baars, J W; Schutte, P F E; Schellens, J H M; Beijnen, J H

    2008-12-01

    A breast cancer patient experienced an accidental propofol extravasation in the dorsum of her hand during a Port-A-Cath replacement. She had heavy pain which was treated with analgesics. The patient's hand was cooled and kept in an upright position. Three days later the patient received her last AC (adriamycin/cyclophosphamide) course without complications. Propofol extravasation did not result in tissue necrosis in this case. AC chemotherapy could be administered safely 3 days after propofol extravasation. PMID:18753182

  9. Reversible posterior leukoencephalopathy after combination chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Honkaniemi, J.; Latvala, M.; Hietaharju, A.; Ollikainen, J.; Vaehaemaeki, L.; Frey, H. [Department of Neurology and Rehabilitation, Univ. of Tampere (Finland); Kaehaerae, V.; Dastidar, P. [Department of Radiology, Univ. of Tampere (Finland); Salonen, T. [Department of Internal Medicine, Univ. of Tampere (Finland); Keskinen, L.; Kellokumpu-Lehtinen, P. [Department of Oncology, Univ. of Tampere (Finland)

    2000-12-01

    We describe a young woman with Burkitt's lymphoma, treated with intravenous adriamycine and cyclophosphamide and intrathecal cytarabine. She developed a reversible posterior leukoencephalopathy syndrome (RPLS) with typical MRI findings. Diffusion-weighted images during the first days after the onset of symptoms predicted a small irreversible lesion in the frontal lobe, verified on T2-weighted images 1 month later. The patient showed full recovery after high-dose steroid treatment. (orig.)

  10. Flow cytometric applications of tumor biology: prospects and pitfalls

    International Nuclear Information System (INIS)

    A brief review of cytometry instrumentation and its potential applications in tumor biology is presented using our recent data. Age-distribution measurements of cells from spontaneous dog tumors and cultured cells after exposure to x rays, alpha particles, or adriamycin are shown. The data show that DNA fluorescence measurements have application in the study of cell kinetics after either radiation or drug treatment. Extensive and careful experimentation is needed to utilize the sophisticated developments in flow cytometry instrumentation

  11. Cbl-b inhibits P-gp transporter function by preventing its translocation into caveolae in multiple drug-resistant gastric and breast cancers

    OpenAIRE

    Zhang, Ye; Qu, Xiujuan; Teng, Yuee; Li, Zhi; Xu, Ling; Liu, Jing; MA, YANJU; Fan, Yibo; Li, Ce; Liu, Shizhou; Wang, Zhenning; Hu, Xuejun; Zhang, Jingdong; Liu, Yunpeng

    2015-01-01

    The transport function of P-glycoprotein (P-gp) requires its efficient localization to caveolae, a subset of lipid rafts, and disruption of caveolae suppresses P-gp transport function. However, the regulatory molecules involved in the translocation of P-gp into caveolae remain unknown. In the present study, we showed that c-Src dependent Caveolin-1 phosphorylation promoted the translocation of P-gp into caveolae, resulting in multidrug resistance in adriamycin resistant gastric cancer SGC7901...

  12. Fibronectin-mediated Calmette-Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response.

    OpenAIRE

    Kavoussi, L R; Brown, E J; Ritchey, J K; Ratliff, T L

    1990-01-01

    Adjuvant intravesical Calmette-Guerin bacillus (BCG) is an effective treatment for superficial bladder cancer. The mechanisms by which BCG mediates antitumor activity are not known. We investigated the initial interaction of BCG with the bladder mucosa to determine whether binding was essential for the development of antitumor activity. Herein, we show that bladder urothelial disruption induced by acrolein, adriamycin, or electrocautery resulted in BCG binding in areas of urothelial damage. B...

  13. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells.

    OpenAIRE

    Roninson, I B; Chin, J E; Choi, K. G.; Gros, P.; Housman, D.E.; Fojo, A; Shen, D. W.; Gottesman, M M; Pastan, I

    1986-01-01

    The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that multidrug-resistant Chinese hamster cell lines contain an amplified, transcriptionally active DNA sequence designated mdr. This report presents evidence that multidrug-resistant sublines of human KB carcinoma cells, selected for resistance to either colchicine, vinblastine, or Adriamycin (doxorubicin), d...

  14. Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene.

    OpenAIRE

    Shen, D. W.; Fojo, A; Roninson, I B; Chin, J E; Soffir, R; Pastan, I; Gottesman, M M

    1986-01-01

    Mouse NIH 3T3 cells were transformed to multidrug resistance with high-molecular-weight DNA from multidrug-resistant human KB carcinoma cells. The patterns of cross resistance to colchicine, vinblastine, and doxorubicin hydrochloride (Adriamycin; Adria Laboratories Inc.) of the human donor cell line and mouse recipients were similar. The multidrug-resistant human donor cell line contains amplified sequences of the mdr1 gene which are expressed at high levels. Both primary and secondary NIH 3T...

  15. Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene.

    OpenAIRE

    Del Bufalo, D; Biroccio, A; Soddu, S; Laudonio, N; D'Angelo, C.; Sacchi, A; Zupi, G.

    1996-01-01

    Lonidamine, a dichlorinated derivative of indazole-3-carboxylic acid, was shown to play a significant role in reversing or overcoming multidrug resistance. Here, we show that exposure to 50 microg/ml of lonidamine induces apoptosis in adriamycin and nitrosourea-resistant cells (MCF-7 ADR(r) human breast cancer cell line, and LB9 glioblastoma multiform cell line), as demonstrated by sub-G1 peaks in DNA content histograms, condensation of nuclear chromatin, and internucleosomal DNA fragmentatio...

  16. Immature ovarian teratoma in a postmenopausal woman

    DEFF Research Database (Denmark)

    Ornvold, K; Detlefsen, G U; Horn, T;

    1987-01-01

    We report the first case of immature ovarian teratoma occurring after menopause in a 57-year-old, 3 years postmenopausal woman. Within one year after resection of the teratoma she developed peritoneal botryoid rhabdomyosarcoma, which probably originated from initially unrecognized rhabdomyoblasts...... in the teratoma. The patient died 6 months later from progressive disease after a transient adriamycin-induced tumor response. The literature on ovarian immature teratoma and ovarian rhabdomyosarcoma is briefly reviewed, and the available treatment is discussed....

  17. 肺癌の治療に関する基礎的並びに臨床的研究 第1編 実験肺癌(Lewis lung carcinoma)をモデルとした肺癌の化学療法に関する研究

    OpenAIRE

    村上, 直樹

    1988-01-01

    Lewis lung carcinoma in an advanced stage was evaluated as a model of human lung cancer for screening drugs and drug combinations. The tumor was fairly resistant to drugs when therapy was started 7 days after tumor transplantation. Among the drugs which have been used conventionally in the treatment of human lung cancer, cyclophosphamide was the only are distinctly active against the tumor. BCNU, a nitrosourea, was fairly active; however, adriamycin, methotrexate and vincristine were only mar...

  18. Iatrogenic Pulmonary Nodule in a Heart Transplant Recipient

    OpenAIRE

    Mehta, Atul C.; Juan Wang; Jarmanjeet Singh; Joseph Cicenia

    2014-01-01

    A 58-year-old female with a history of non-Hodgkin lymphoma and end-stage nonischemic cardiomyopathy from Adriamycin toxicity underwent orthotic heart transplantation during June 2013. She developed shortness of breath in September 2013 and was suspected to have invasive pulmonary aspergillosis. A flexible bronchoscopy (FB) with a transbronchial biopsy (TBBx) was performed. She was found to have a focal lung nodule in the same location at the site of the TBBx on day 13 after the FB. Spontaneo...

  19. Response to X-radiation and cytotoxic drugs of clonal subpopulations of different ploidy and metastatic potential isolated from RIF-1 mouse sarcoma.

    OpenAIRE

    Reeve, J. G.; Wright, K. A.; Twentyman, P. R.

    1983-01-01

    Clonal subpopulations of different ploidy values and metastatic capacities, isolated from the RIF-1 mouse sarcoma, have been tested for in vitro X-radiation sensitivity, for in vitro sensitivity to adriamycin and for in vitro and in vivo sensitivity to melphalan and CCNU. Following X-radiation, no consistent differences in the survival curve characteristics (Do and n) of diploid, tetraploid and octoploid cells were observed. In addition no relationship between radiation response and metastati...

  20. Plasma Membrane Lesions In Anthracycline-Resistant Tumor Cells Probed Using A Fluorescent Dye

    Science.gov (United States)

    Burke, Thomas G.; Doroshow, James H.

    1989-06-01

    Human cancer cells selected for resistance to several structurally unrelated cytotoxic drugs are known to display plasma membrane alterations such as amplified levels of a variety of glycoproteins, modifications in lipid composition, alterations in membrane fluidity and increased cellular fragility to osmotic shock. We have studied the plasma membrane fluidity of HL60 human leukemia cells and MCF-7 human breast cancer cells that have been selected for acquired resistance against the cytocidal effects of the anthracycline anticancer drug Adriamycin. Fluidity measurements were accomplished by evaluating the fluorescence anisotropy of the plasma membrane specific probe trimethylamino-1,6-dipihenylhexatriene (TMA.DPH) bound to whole, living cells. TMA.DPH anisotropy values for MCF-7 sensitive and 12-fold resistant cells were 0.306 and 0.285, respectively, while anisotropy values for HL-60 sensitive and 80-fold resistant cells lines were 0.310 and 0.295, respectively. In all cases, cell viability exceeded 97% and anisotropy values were subject to a day-to-day uncertainty of +/-2%. Our results demonstrate that increased plasma membrane fluidity apparently accompanies the development of resistance in both cell lines. Because it is known that increased membrane fluidity results in significantly decreased Adriamycin binding in artificial membrane systems, we propose here that decreased drug associations with fluidized, plasma membrane lipid bilayer regions may be a mechanism which contributes, in part, to the reduced rates of drug accumulation observed in HL60 and MCF-7 cells resistant to Adriamycin.

  1. Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

    International Nuclear Information System (INIS)

    Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O2 consumption with half-maximal inhibitory concentrations (IC5) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC5 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin

  2. Reversion of P-Glycoprotein-Mediated Multidrug Resistance in Human Leukemic Cell Line by Diallyl Trisulfide

    Directory of Open Access Journals (Sweden)

    Qing Xia

    2012-01-01

    Full Text Available Multidrug resistance (MDR is the major obstacle in chemotherapy, which involves multiple signaling pathways. Diallyl trisulfide (DATS is the main sulfuric compound in garlic. In the present study, we aimed to explore whether DATS could overcome P-glycoprotein-(P-gp-mediated MDR in K562/A02 cells, and to investigate whether NF-κB suppression is involved in DATS-induced reversal of MDR. MTT assay revealed that cotreatment with DATS increased the response of K562/A02 cells to adriamycin (the resistance reversal fold was 3.79 without toxic side effects. DATS could enhance the intracellular concentration of adriamycin by inhibiting the function and expression of P-gp, as shown by flow cytometry, RT-PCR, and western blot. In addition, DATS resulted in more K562/A02 cell apoptosis, accompanied by increased expression of caspase-3. The expression of NF-κB/p65 (downregulation was significantly linked to the drug-resistance mechanism of DATS, whereas the expression of IκBα was not affected by DATS. Our findings demonstrated that DATS can serve as a novel, nontoxic modulator of MDR, and can reverse the MDR of K562/A02 cells in vitro by increasing intracellular adriamycin concentration and inducing apoptosis. More importantly, we proved for the first time that the suppression of NF-κB possibly involves the molecular mechanism in the course of reversion by DATS.

  3. Reversion of p-glycoprotein-mediated multidrug resistance in human leukemic cell line by diallyl trisulfide.

    Science.gov (United States)

    Xia, Qing; Wang, Zhi-Yong; Li, Hui-Qing; Diao, Yu-Tao; Li, Xiao-Li; Cui, Jia; Chen, Xue-Liang; Li, Hao

    2012-01-01

    Multidrug resistance (MDR) is the major obstacle in chemotherapy, which involves multiple signaling pathways. Diallyl trisulfide (DATS) is the main sulfuric compound in garlic. In the present study, we aimed to explore whether DATS could overcome P-glycoprotein-(P-gp-)mediated MDR in K562/A02 cells, and to investigate whether NF-κB suppression is involved in DATS-induced reversal of MDR. MTT assay revealed that cotreatment with DATS increased the response of K562/A02 cells to adriamycin (the resistance reversal fold was 3.79) without toxic side effects. DATS could enhance the intracellular concentration of adriamycin by inhibiting the function and expression of P-gp, as shown by flow cytometry, RT-PCR, and western blot. In addition, DATS resulted in more K562/A02 cell apoptosis, accompanied by increased expression of caspase-3. The expression of NF-κB/p65 (downregulation) was significantly linked to the drug-resistance mechanism of DATS, whereas the expression of IκBα was not affected by DATS. Our findings demonstrated that DATS can serve as a novel, nontoxic modulator of MDR, and can reverse the MDR of K562/A02 cells in vitro by increasing intracellular adriamycin concentration and inducing apoptosis. More importantly, we proved for the first time that the suppression of NF-κB possibly involves the molecular mechanism in the course of reversion by DATS. PMID:22919419

  4. Characterization of naturally acquired multiple-drug resistance of Yoshida rat ascites hepatoma AH66 cell line.

    Science.gov (United States)

    Miyamoto, K; Wakabayashi, D; Minamino, T; Nomura, M; Wakusawa, S; Nakamura, S

    1996-01-01

    Characteristics of multiple-drug resistance of rat ascites hepatoma AH66, a cell line induced by dimethylaminoazobenzene and established as a transplantable tumor, were compared with those of AH66F, a drug sensitive line obtained from AH66. The AH66 cell line was resistant to vinblastine, adriamycin, SN-38 an active form of camptothesine, etoposide, and clorambucil by 10-fold or more than the AH66F cell line. The resistance of AH66 cells to vinblastine, adriamycin, and SN-38 was closely related to P-glycoprotein overexpression in the plasma membrane, because the resistance was significantly inhibited by verapamil. AH66 cells contained much glutahione and had a high activity of glutathione S-transferase P-form (GST-P), compared with AH66F cells, and resistance to clorambucil was decreased by treatment with buthionine sulfoximine, an inhibitor of glutathione synthesis. AH66 cells have a similar topoisomerase I activity, but about 6 times lower topoisomerase II activity than AH66F cells. Therefore, the resistance to etoposide and a part of the resistance to adriamycin of AH66 cells seems to depend upon this low topoisomerase II activity. These results, show that the AH66 cell line has high multiple-drug resistance compared with the AH66F cell line, by several mechanisms. Consequently, the AH66 and AH66F cell lines are useful to study naturally acquired multiple-drug resistance of hepatomas. PMID:8702243

  5. Anthracyclines.

    Science.gov (United States)

    Sinha, B K; Politi, P M

    1990-01-01

    After twenty years, understanding the mechanisms of tumor cells kill by anthracyclines still remains an active area of research. Of many mechanisms described for this class of drugs, efforts in the last year have focused on defining the role of free radical formation, topoisomerase II-induced DNA breakage, and P-170-dependent cellular accumulation of anthracyclines in tumor cell kill and resistance. First, in a number of tumor cell lines, the formation of free radical species from anthracyclines has been implicated in the cell killing. Modulation of detoxification pathways in a drug-resistant cell line e.g depletion of GSH, a substrate for peroxidase and transferase, enhanced both the formation of oxy-radicals and adriamycin cytotoxicity. It should be noted, however, that these findings are not true for every cell line examined, and free radical-mediated tumor kill may be cell- or tissue-specific. Second, anthracyclines-mediated topo II-dependent DNA cleavage was observed in most cell lines and reduced breaks were found in resistant cells. The decrease in single-strand breaks, however, neither correlated with the degree of resistance nor with differences in the relative topo II activity, which was in most cases only two-fold less in resistant cells than in sensitive cells. Finally, the reduced accumulation of the drug does not appear to be the only contributing factor in multidrug resistant cells and P-170 is not the only protein overexpressed in certain cells, e.g., an 85,000 Da protein may also be linked to adriamycin resistance. Although GST protein is overexpressed in most adriamycin resistant cells along with mdr1 gene, current evidence suggests that this protein may not be directly involved in adriamycin resistance. Taken together, both the mechanism of action and resistance to this class of drug likely vary among cell lines. Clinical studies in the past year have brought about interesting refinements in anthracycline-containing chemotherapy; ICRF-187 (by

  6. The anti-hepatoma effect of nanosized Mn-Zn ferrite magnetic fluid hyperthermia associated with radiation in vitro and in vivo.

    Science.gov (United States)

    Lin, Mei; Zhang, Dongsheng; Huang, Junxing; Zhang, Jia; Xiao, Wei; Yu, Hong; Zhang, Lixin; Ye, Jun

    2013-06-28

    Joint therapy is a promising area of study in cancer treatment. In this paper, we prepared Mn-Zn ferrite (Mn0.5Zn0.5Fe2O4) magnetofluid using PEI as a surfactant, and investigated the anticancer effect of Mn0.5Zn0.5Fe2O4 magnetic fluid hyperthermia (MFH) combined with radiotherapy on hepatocellular carcinoma. Both in vitro and in vivo results suggest that this combined treatment with MFH and radiation has a better therapeutic effect than either of them alone. The apoptotic rate and necrotic rate of the combined treatment group was 38.80 and 25.20%, respectively. In contrast, it was only 7.49 and 3.62% in the radiation-alone group, 15.23 and 7.90% in the MFH-alone group, only 3.52 and 2.16% in the blank control group, and 23.56 and 27.56% in the adriamycin group. The cell proliferation inhibition rate of the combined treatment group (88.5%) was significantly higher than that of the radiation-alone group (37.5%), MFH-alone group (60.6%) and adriamycin group (70.6%). The tumor volume inhibition and mass inhibition rate of the combined treatment group was 87.62 and 88.62%, respectively, obviously higher than the 41.04 and 34.20% of the radiation-alone group, 79.87 and 77.92% of the MFH-alone group and 71.76 and 66.87% of the adriamycin group. It is therefore concluded that this combined application of MFH and radiation can give good synergistic and complementary effects, which offers a viable approach for treatment of cancer. PMID:23708194

  7. Involvement of c-Jun N-terminal kinase in reversal of multidrug resistance of human leukemia cells in hypoxia by 5-bromotetrandrine.

    Science.gov (United States)

    Zhang, Wei; Chen, Bao-an; Jin, Jun-fei; He, You-ji; Niu, Yi-qi

    2013-11-01

    5-Bromotetrandrine (BrTet), a candidate multidrug resistance (MDR) modulator, is a potential compound for use in cancer therapy when combined with anticancer agents such as daunorubicin (DNR) and paclitaxel. The purposeof this study was to investigate the mechanism of reversal of P-glycoprotein (P-gp)-mediated MDR by BrTet and the involvement of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway in both adriamycin-sensitive K562 and adriamycin-resistant K562 (KA) leukemia cells in hypoxia. The combination of BrTet and DNR decreased both phosphorylated JNK1/2 and MDR1/P-gp levels under hypoxic conditions. Furthermore, a pharmacological inhibitor of JNK, SP600125, or small interfering RNA (siRNA) oligonucleotides to both JNK1 and JNK2 reversed BrTet- or DNR-induced JNK phosphorylation and MDR1/P-gp levels. We further demonstrated that the decreased JNK phosphorylation and MDR1/P-gp levels were associated with a significant increase in intracellular accumulation of DNR, which dramatically enhanced the sensitivity of drug-resistant KA cells to DNR, and led to cellular apoptosis through activation of the caspase-3 pathway. It is concluded that using BrTet in combination with other chemotherapeutic agents and pharmacological inhibitors of JNK can abrogate the P-gp-induced MDR in adriamycin-resistant K562 cells, which has potential clinical relevance in cancer therapy for chemotherapeutic-resistant human leukemia. PMID:23418897

  8. Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability

    OpenAIRE

    Wang, Donglai; Zhou, Jingyi; Liu, Xiangyu; Lu, Danyu; Shen, Changchun; Du, Yipeng; Wei, Fu-Zheng; Song, Boyan; Lu, Xiaopeng; Yu, Yu; Wang, Lina; Zhao, Ying; Wang, Haiying; Yang, Yang; Akiyama, Yoshimitsu

    2013-01-01

    Suppressor of variegation 3–9 homolog 1 (SUV39H1), a histone methyltransferase, catalyzes histone 3 lysine 9 trimethylation and is involved in heterochromatin organization and genome stability. However, the mechanism for regulation of the enzymatic activity of SUV39H1 in cancer cells is not yet well known. In this study, we identified SET domain-containing protein 7 (SET7/9), a protein methyltransferase, as a unique regulator of SUV39H1 activity. In response to treatment with adriamycin, a DN...

  9. Radiation sensitizers

    International Nuclear Information System (INIS)

    The following classes of radiosensitizers are discussed: electron affinic compounds, pyrimidine analogs, and antibiotics. Metronidazole and nitroimidazole are discussed as examples of electron-affinic compounds. Studies on the enhancement ratio for sensitization of x-irradiated hamster cells showed that these drugs sensitize at concentrations much lower than the toxic concentrations. Criteria for a clinically useful hypoxic cell sensitizer are listed and mechanisms of electron-affinic sensitizers are discussed. The radiosensitizing effects of the pyrimidine analogs, BUDR, BCDR, IUDR, CUDR, and FUDR, are examined and the enhancement of radiation effects by the chemotherapeutic agent, 5-fluorouracil, is discussed. Other agents discussed are methotrexate, actinomycin D, bleomycin, and adriamycin

  10. Acute Local Spontaneous and Profuse Gingival Hemorrhage during Neoadjuvant Treatment with Paclitaxel and Trastuzumab

    Directory of Open Access Journals (Sweden)

    Nima D. Sarmast

    2016-06-01

    Full Text Available This case report describes a 33-year-old female currently undergoing breast cancer treatment following the AC-T-T (doxorubicin hydrochloride (Adriamycin and cyclophosphamide followed by paclitaxel (Taxol and trastuzumab (Herceptin treatment regimen. Her chief complaint at the time of the emergency visit at the dental office was that she had an episode of profuse spontaneous bleeding located at the palatal gingiva in the maxilla between the left central and lateral incisor. To our knowledge, this is a novel finding related to the medications she is utilizing and should be further investigated.

  11. 三维荧光光谱结合交替三线性分解二阶校正法同时测定血浆样中三种抗癌药物含量%Simultaneous determination of three anticancerogens in plasma samples using second-order calibration method based on alternating trilinear decomposition coupled with fluorescence spectroscopy

    Institute of Scientific and Technical Information of China (English)

    王予; 吴海龙; 于永杰; 王建瑶; 赵娟; 陈瑶; 张喜华; 俞汝勤

    2012-01-01

    姜黄素、阿霉素和白藜芦醇对多种恶性肿瘤的治愈皆有一定的疗效,且其联合用药对癌细胞的抑制效果更加显著.本文采用三维激发发射荧光光谱结合基于交替三线性分解(Alternating Trilinear Decomposition,ATLD)算法的化学计量学二阶校正法,同时对血浆样中姜黄素、盐酸阿霉素和白藜芦醇的含量进行了定量分析研究.当量测体系的组分数预估计取4时,ATLD方法解析得到的血浆样中姜黄素、盐酸阿霉素和白藜芦醇的平均回收率分别为(91.4±1.1)%、(104.5±2.8)%和(103.4±4.7)%.实验结果表明,此法能够解决干扰共存和荧光光谱重叠下血浆样中姜黄素、盐酸阿霉素和白藜芦醇的直接、快速、同时定量分析的难题.%Curcumin, adriamycin and resveratrol are effective for curing many kinds of cancer, and combination of them can contribute to the prevention of cancer cells more notably. In this paper, curcumin, adriamycin and resveratrol were determined in plasma samples simultaneously by using three-way excitation-emission fluorescence spectra with second-order calibration in chemometrics based on the alternating trilinear decomposition (ATLD) algorithm. When the estimated number of components was set to 4, the obtained average recoveries of curcumin, adriamycin hydrochloride and resveratrol in plasma samples were (91.4±1.1)%, (104.5±2.8)% and (103.42±4.67)% for ATLD, respectively. The experiment results indicated that the proposed method could be applied to simultaneously quantify the curcumin, adriamycin hydrochloride and resveratrol contents in plasma samples even in the presence of unknown interferences.

  12. Normal tissue toxicity of upper hemibody irradiation (UHBI) when used as a non-cross resistant agent in combination with chemotherapy in the treatment of small cell lung cancer (SCLC)

    International Nuclear Information System (INIS)

    Previous studies at this Institute have investigated the use of HBI as a consolidation agent in the treatment of SCLC. The present Phase I-II study investigates the toxicity and efficacy of UHBI used as a non-cross resistant alternating agent with chemotherapy early in the induction phase of treatment of all stages of SCLC. Toxicity due to the combined effects of chemotherapy plus UHBI is reported as well as effects on bone marrow, lungs and GI tract. The increased incidence of pneumonitis observed in the present study points to a possible interaction of these modalities when HBI is being used as an alternating agent with Cisplatin and Adriamycin

  13. Extra-axial primary non-Hodgkin's CNS lymphoma mimicking meningioma, in a 5-year-old immunocompetent child: a rare entity.

    Science.gov (United States)

    Bhaskar, Mukesh Kumar; Ojha, Balkrishna; Jaiswal, Manish; Sagar, Mala

    2016-01-01

    We describe a case of a 5-year-old immunocompetent girl who presented with features of raised intracranial pressure with left eye ptosis of 1-month duration. CT scan and MRI of the brain showed an extra-axial, intensely contrast enhancing lesion in the left temporoparieto-occipital region, consistent with meningioma. On open tissue biopsy and immunohistochemistry staining, a diagnosis of B cell non-Hodgkin's lymphoma was made. Six cycles of chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone regimen were given and showed a good clinical outcome without any recurrence during follow-up of 5 months. PMID:27118750

  14. Progress in Diagnosis and Treatment of Small Cell Carcinoma of the Cervix

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Small cell carcinoma of the cervix (SCCC) belongs to the neuroendocrine carcinomas, and it is a rare gynecological tumor of high-potential malignancy. It has a poorer prognosis compared to cervical squamous cancer or adenocarcinoma, and the therapeutic regimen of the disease differs. Diagnosis is based on pathomorphological characteristics, i.e., the small and round cancer cells (oat cell) which are uniform in shape and size, with the immunohistochemical marker helpful for diagnosis. Combined therapy is first recommended. Postoperative chemotherapy with platinum/etoposide (PE), vincristine/adriamycin/cyclophosphamide (VAC) and taxel/carboplatin (TP) can markedly improve the prognosis of early SCCC patients.

  15. Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors.

    OpenAIRE

    Koutsilieris, M; Reyes-Moreno, C.; Choki, I.; Sourla, A.; Doillon, C.; Pavlidis, N.

    1999-01-01

    One-third of women with breast cancer will develop bone metastases and eventually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta 1 (TGF-beta1) to alter the effects of adriamycin on cell cycle and apoptosis of estrogen receptor negative (ER-) MDA-MB-231 and positive (ER+) MCF-7 breast cancer cells, usi...

  16. Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.

    OpenAIRE

    Sugimoto, Y.; Roninson, I B; Tsuruo, T.

    1987-01-01

    Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the ...

  17. Expression of a full-length cDNA for the human "MDR1" gene confers resistance to colchicine, doxorubicin, and vinblastine.

    OpenAIRE

    Ueda, K; Cardarelli, C; Gottesman, M M; Pastan, I

    1987-01-01

    Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former generic name adriamycin) is associated with overexpression of the "MDR1" gene, which encodes P-glycoprotein. We previously have isolated an overlapping set of cDNA clones for the human MDR1 gene from multidrug-resistant KB cells. Here we report the construction of a full-length cDNA for the human...

  18. An unusual case of giant cell myocarditis missed in a Heartmate-2 left ventricle apical-wedge section: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Anderson Kim

    2013-01-01

    Full Text Available Abstract Herein we present a case of fulminant myocarditis in a woman previously treated for B-cell lymphoma. While the clinical context was suggestive of adriamycin-induced cardiomyopathy, the initial pathology of the Heartmate-2 apical core showed lymphocytic myocarditis. After 8 months of stability, the patient presented with progressive heart failure and recurrent ventricular arrhythmias. An endomyocardial biopsy revealed findings typical of giant cell myocarditis (GCM; poor response to immunosuppressive therapy and marked hemodynamic instability led to urgent transplantation. To our knowledge, this is the first reported case of GCM following an acute lymphocytic myocarditis and the second GCM case associated with B-cell lymphoma.

  19. Prevention of doxorubicin-induced alopecia by scalp cooling in patients with advanced breast cancer.

    OpenAIRE

    Anderson, J E; Hunt, J. M.; Smith, I E

    1981-01-01

    Scalp cooling with gel packs was used to try to prevent alopecia in 31 patients being treated with doxorubicin (Adriamycin), 29 for advanced breast carcinoma and two for carcinoid tumour. Twenty-eight of the 31 patients tolerated the procedure well, and 22 of these had either no hair loss or only slight loss which remained acceptable and did not require a wig. The main factor limiting success was biochemical impairment of liver function, which occurred in nine patients; of these, six had seve...

  20. A case of cardiac sudden death related to abnormality of sympathetic nervous disturbance detected by 123I-metaiodobenzylguanidine (MIBG)

    International Nuclear Information System (INIS)

    A case of cardiac sudden death was reported. A female, 64 years old patient with multiple myeloma had been treated with total dose of 790 mg of adriamycin. Although treadmill examination, dobutamine-loaded cardiac echography and thallium-loaded myocardial scintigraphy gave normal findings, Holter ECG revealed bigeminy and discontinuous ventricular tachycardia. Mexiletine was not tolerated. 123I-MIBG image gave deficit of lateral to posterior wall and increased washing rate of 65%. At 36 days after hospitalization, the ventricular tachycardia changed to fatal fibrillation. The sympathetic nervous disturbance detected by the enhanced washing rate of 123I-MIBG might have participated in the death. (K.H.)

  1. Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents.

    Science.gov (United States)

    Zhu, Jianyong; Wang, Ruimin; Lou, Lanlan; Li, Wei; Tang, Guihua; Bu, Xianzhang; Yin, Sheng

    2016-07-14

    The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1-13), of which eight (1-8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14-35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators. The activity was evaluated through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human breast adenocarcinoma cell line MCF-7 (MCF-7/ADR). Compounds 19, 25, and 26 were identified as potent MDR modulators with greater chemoreversal ability and less cytotoxicity than the third-generation drug tariquidar. The structure-activity relationship (SAR) was discussed, which showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. Compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. PMID:27328029

  2. Effects of Hypoxia on Expression of P-gp and Mutltidrug Resistance Protein in Human Lung Adenocarcinoma A549 Cell Line

    Institute of Scientific and Technical Information of China (English)

    XIA Shu; YU Shiying; YUAN Xianglin

    2005-01-01

    Summary: To study the effects of hypoxia on the expression of P-gp and mutltidrug resistance protein in human lung adenocarcinoma A549 cell line, and to explore the probable mechanism of hypoxia in tumor cell of MDR. The expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein was immunohistochemically detected by culturing human lung adenocarcinoma A549 cell under hypoxia (2 % O2) for 24 h. After interaction with adriamycin or cisplatin under hypoxia (2 % O2) for 24 h, the cell survival rate was detected by MTT. Our results showed that the expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein under hypoxia were higher than the expression under normoxia, and correlations between the expression of HIF-1α and P-gp or multidrug resistance-associated protein was observed (P<0.05). The resistance of adriamycin of A549 cell was enhanced under hypoxia. It is concluded that the resistance of tumor chemotherapy is enhanced in hypoxia. The expression of HIF-1α is obviously correlated with the expression of P-gp and mutltidrug resistance protein.

  3. Cytotoxicity, differentiating activity and metabolism of tiazofurin in human neuroblastoma cells.

    Science.gov (United States)

    Pillwein, K; Schuchter, K; Ressmańn, G; Gharehbaghi, K; Knoflach, A; Cermak, B; Jayaram, H N; Szalay, S M; Szekeres, T; Chiba, P

    1993-08-19

    The IMP dehydrogenase inhibitor, tiazofurin (TR)-2-beta-D-ribofuranosylthiazole-4-carboxamide, which exhibited oncolytic activity in patients with chronic myelogenous leukaemia (CML) in blast crisis was found to inhibit the growth of human neuroblastoma SK-N-SH cells with an IC50 of 4.2 microM. TR treatment of cells perturbed nucleic acid and catecholamine pathways. As biochemical markers of TR action decreased cellular GTP pools, increased inosine and hypoxanthine concentrations and depleted dopamine content were found. Incubation of tumour specimens obtained from paediatric patients with grade-IV neuroblastoma with TR resulted in the formation of the active metabolite, thiazole-4-carboxamide adenine dinucleotide, in concentrations sufficient to inhibit tumour growth. Cytotoxic and biochemical effects of TR were enhanced by combining it with allopurinol (an inhibitor of xanthine dehydrogenase), and hypoxanthine (an alternate substrate for hypoxanthine-guanine phosphoribosyltransferase). Induction of transdifferentiation of SK-N-SH cells from a neuroblast to an epitheloid, substrate-adherent phenotype was more pronounced with TR than with all-trans-retinoic acid. Transdifferentiating treatment with TR resulted in a 2-fold-enhanced sensitivity towards adriamycin. However, differentiation with all-trans-retinoic acid rendered the cells more resistant to adriamycin. Our results suggest that TR might be a promising agent for the treatment of children suffering from neuroblastoma. PMID:8344756

  4. Inhibition of integrin α2β1 ameliorates glomerular injury.

    Science.gov (United States)

    Borza, Corina M; Su, Yan; Chen, Xiwu; Yu, Ling; Mont, Stacey; Chetyrkin, Sergei; Voziyan, Paul; Hudson, Billy G; Billings, Paul C; Jo, Hyunil; Bennett, Joel S; Degrado, William F; Eckes, Beate; Zent, Roy; Pozzi, Ambra

    2012-06-01

    Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria. PMID:22440900

  5. Multimodality treatment of primary nonresectable intrahepatic cholangiocarcinoma with I-131 anti-CEA: A radiation therapy oncology group study

    International Nuclear Information System (INIS)

    Thirty-seven patients (57% with metastasis and/or who has previously undergone chemotherapy) with primary unresectable intrahepatic cholangiocarcinoma were prospectively treated with external beam radiation therapy, chemotherapy, and I-131 anti-carcinoembryonic antigen (CEA) antibody. The regimen led to partial remission in 26.6% of patients, according to CT scan digitized tumor volume analysis, and in 33.3% (25.9% with partial remission, 7.4% with complete emission) according to physical examination findings. Therapy began with whole liver irradiation (2.1 Gy, 0.3 Gy per fraction, delivered 4 days a week, with 10-MV photons) and, on alternate days, chemotherapy (Adriamycin, 15 mg, + 5-fluorouracil [5-FU], 500 mg). One month later, Adriamycin, 15 mg, + 5-FU, 500 mg, was administered on day 0; 20 mCi of I-131 anti-CEA on day 1; and 10 mCi of I-131 anti-CEA on day 6. Tumor effective half-life was 3-5 days. Median tumor dose (20 mCi + 10 mCi) was 6.2 Gy. Antibody therapy was administered in 2-month cycles. Grade IV thrombocytopenia and leukopenia each occurred in 3.2% of patient administrations. Median survival for the entire group was 6.5 months; for responders, it was 15.2 months. The longest partial remission is presently more than 4 years

  6. Radiation therapy in the management of patients with mesothelioma

    International Nuclear Information System (INIS)

    The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free inteval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months of initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin

  7. Radiation therapy in the management of patients with mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, W. Jr.; Antman, K.H.; Greenberger, J.S.; Weichselbaum, R.R.; Chaffey, J.T.

    1982-01-01

    The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free inteval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months of initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin.

  8. Combined chemotherapy and radiotherapy of localized and metastasizing Ewing's sarcoma

    International Nuclear Information System (INIS)

    Between 1973 and 1978 combined radiotherapy and chemotherapy were given to 22 patients with histologically proven Ewing's sarcoma. The combined chemotherapy consisted of cyclophosphamide, vincristin, adriamycin, as well as dacarbazine in some cases. The neoplasm was a localized one at the beginning of treatment in 14 of the 22. These patients received high-voltage rediotherapy to the primary focus at a focal dose between 42 and 55 Gray (4200-5500 rad), followed by chemotherapy. After 6-8 treatment cycles, adriamycin was replaced by methotrexate. Nine of the 14 patients survived without recurrence for 12 to over 59 months. Eight patients had extensive metastases at the beginning of treatment: they at first received only chemotherapy, followed by radiotherapy or operation, as indicated. Full clinical remission was achieved in five of them: in three this remission has now lasted for more than 18, 40 and 44 months, respectively. These results indicate that (1) additional chemotherapy improves the prognosis of localized Ewing's sarcoma, and (2) even in farprogressed cases the combination of chemotherapy and radiotherapy can achieve lasting remission, which may in fact be a true cure. (orig.)

  9. Deactivation of signal transducer and activator of transcription 3 reverses chemotherapeutics resistance of leukemia cells via down-regulating P-gp.

    Directory of Open Access Journals (Sweden)

    Xulong Zhang

    Full Text Available Multidrug resistance (MDR caused by overexpression of p-glycoprotein is a major obstacle in chemotherapy of malignant cancer, which usually is characterized by constitutive activation of signal transducer and activator of transcription 3 (STAT3, but their relation between MDR and STAT3 remains unclear. Here, we showed that STAT3 was overexpressed and highly activated in adriamycin-resistant K562/A02 cells compared with its parental K562 cells. Blockade of activation of STAT3 by STAT3 decoy oligodeoxynucleotide (ODN promoted the accumulation and increased their sensitivity to adriamycin by down-regulating transcription of mdr1 and expression of P-gp, which were further confirmed by using STAT3-specific inhibitor JSI-124. Inhibition of STAT3 could also decrease mdr1 promoter mediated luciferase expression by using mdr1 promoter luciferase reporter construct. Otherwise, activation of STAT3 by STAT3C improved mdr1 transcription and P-gp expression. The ChIP results demonstrated that STAT3 could bind to the potential promoter region of mdr1, and STAT3 decoy depressed the binding. Further mutation assay show +64∼+72 region could be the STAT3 binding site. Our data demonstrate a role of STAT3 in regulation of mdr1 gene expression in myeloid leukemia and suggest that STAT3 may be a promising therapeutic target for overcoming MDR resistance in myeloid leukemia.

  10. Characterization of the evolution of the nutritional condition of patients with breast cancer on chemotherapy

    International Nuclear Information System (INIS)

    Introduction: breast cancer is common in women, and it is usually treated with chemotherapy. It has been asserted that this treatment affects nutritional condition because it produces a gastrointestinal symptomatology and modifies food consumption. Objective: characterize the nutritional condition in women with breast cancer treated with adriamycin and cyclophosphamide (AC). Materials and methods: this study used a prospective, longitudinal design with 25 patients during three continuous cycles of chemotherapy. Food intake and anthropometrical indicators of nutritional status were measured before the treatment and at the beginning of each cycle, and gastrointestinal effects were evaluated weekly. Results: during chemotherapy the consumption of meats, desserts, and bakery products diminished, and piece size and consumption of cheese, fruits, and rice decreased. 40% of women had a nor- mal weight and 40% were overweight before and during treatment. The most frequent gastrointestinal effects were xerostomia (61%) and nausea (55%) 56% of patients presented changes in smell and 47% in taste. the rejected foods were beef, fish, milk, and yogurt. there was a statistically significant association between alterations in smell and taste and food aversion but there was no association between aversions and decreased food intake. Conclusions: the short-term treatment with adriamycin and cyclophosphamide did not produce changes in body weight during chemotherapy and, despite gastrointestinal effects; food intake was not affected in a significant way

  11. Extensive disease small cell carcinoma of the lung; trial of non-cross resistant chemotherapy and consolidation radiotherapy

    International Nuclear Information System (INIS)

    Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (complete and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated

  12. Analysis of local control in patients with non-Hodgkin's lymphoma according to the WHO classification

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, K.; Someya, M.; Nagakura, H.; Oouchi, A.; Nakata, K.; Koito, K.; Hareyama, M. [Dept. of Radiology, Sapporo Medical Univ., School of Medicine, Sapporo (Japan); Satoh, M. [Dept. of Clinical Pathology, Sapporo Medical Univ., School of Medicine, Sapporo (Japan); Kogawa, K. [Dept. of Fourth Internal Medicine, Sapporo Medical Univ., School of Medicine, Sapporo (Japan); Himi, T. [Dept. of Otorhinolaryngology, Sapporo Medical Univ., School of Medicine, Sapporo (Japan)

    2005-06-01

    Purpose: to analyze the influence of radiotherapy doses, chemotherapy doses, and clinical parameters on in-field disease control to assess the optimal radiation doses for treatment of non-Hodgkin's lymphoma according to the newly proposed WHO classification. Patients and methods: subjects consisted of 35 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type, 75 diffuse large B-cell lymphomas (DLBCL), 14 follicular lymphomas, 17 extranodal natural killer (NK)/T-cell lymphomas, nasal type, eight unclassified peripheral T-cell lymphomas, four anaplastic large-cell lymphomas, T/null cell type, and five others. 59 patients received radiotherapy alone. 98 patients received CHOP, modified CHOP, or more intensive chemotherapy, and six patients were treated with other combination. Results: no patients with MALT lymphoma had in-field local recurrence. There were no recurrences in DLBCL patients who received chemotherapy in which the doses of adriamycin were > 200 mg/m{sup 2}, nor in DLBCL patients who were treated with > 45 Gy. Only nine of 15 patients with T-cell lymphoma treated with {<=} 50 Gy and three of five patients treated with > 50 Gy had local control. The dose of adriamycin had no influence on local control of T-cell lymphoma. Conclusion: T/NK-cell lymphomas were more radioresistant than B-cell lymphomas. The prognosis for peripheral T/NK-cell lymphomas is poor even when treated by irradiation combined with chemotherapy. (orig.)

  13. Feasibility of Bone Marrow Stromal Cells Autologous Transplantation for Dilated Cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    ZHOU Cheng; YANG Chenyuan; XIAO Shiliang; FEI Hongwen

    2007-01-01

    The feasibility of bone marrow stromal cells autologous transplantation for rabbit model of dilated cardiomyopathy induced by adriamycin was studied. Twenty rabbits received 2 mg/kg of adriamycin intravenously once a week for 8 weeks (total dose, 16 mg/kg) to induce the cardiomyopathy model with the monitoring of cardiac function by transthoracic echocardiography. Marrow stromal cells were isolated from cell-transplanted group rabbits and were culture-expanded on the 8th week. On the 10th week, cells were labeled with 4,6-diamidino-2-phenylindole (DAPI), and then injected into the myocardium of the same rabbits. The results showed that viable cells labeled with DAPI could be identified in myocardium at 2nd week after transplantation. Histological findings showed the injury of the myocardium around the injection site was relieved with less apoptosis and more expression of bcl-2. The echocardiography found the improvement of local tissue movement from (2.12±0.51) cm/s to (3.81±0.47) cm/s (P<0.05) around the inject site, but no improvement of heart function as whole. It was concluded bone marrow stromal cells transplantation for dilated cardiomyopathy was feasibe. The management of cells in vitro, the quantity and the pattern of the cells transplantation and the action mechanism still need further research.

  14. Isolation and partial characterisation of a mammalian cell mutant hypersensitive to topoisomerase II inhibitors and X-rays

    International Nuclear Information System (INIS)

    The authors have isolated, following one-step mutagenesis, a Chinese hamster ovary cell mutant hypersensitive to the intercalating agent, adriamycin. This agent exerts at least part of its cytotoxic action via inhibition of the nuclear enzyme, topoisomerase II. The mutant, designated ADR-3, showed hypersensitivity to all classes of topoisomerase II inhibitors, inlcuding actinomycin D, amsacrine (m-AMSA), etoposide (VP16) and mitoxantrone. ADR-3 cells also showed cross-sensitivity to ionizing radiation, but not no UV light. Topoisomerase II activity was elevated to a small but significant degree in ADR-3 cells, and this was reflected in a 1.5-fold higher level of topoisomerase II protein in ADR-3 than in CHO-K1 cells, as judged by Western blotting. ADR-3 cells were hypersensitive to cumene hydroperoxide but cross-resistant to hydrogen peroxide, suggesting possible abnormality in the detoxification of peroxides by glutathione peroxidase or catalase. Glutathione peroxidase activity against hydroperoxide was elevated to a small but significant extent in mutant cells. Catalase levels were not significantly different in ADR-3 and CHO-K1 cells. ADR-3 cells were recessive in hybrids with parental CHO-K1 cells with respect to sensitivity to topoisomerase II inhibitors and X-rays, and represent a different genetic complementation group from the previously reported adriamycin-sensitive mutant, ADR-1. (author). 34 refs.; 5 figs.; 3 tabs

  15. The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use.

    Science.gov (United States)

    Cassinelli, Giuseppe

    2016-06-01

    In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery. PMID:27103205

  16. Synthesis and evaluation of L-glutamic acid analogs as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Viswanathan C

    2008-01-01

    Full Text Available Four N-(benzenesulfonyl-L-glutamic acid bis(p-substituted phenylhydrazides were synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3 prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog with the nitro group substitution exhibited potent activity (% Inhibition 84.7 and 72.0 in DU-145 and PC-3 respectively at 80 mg/ml concentration. Another series of substituted 1-(benzenesulfonyl-5-oxopyrrolidine 2-carboxamides (11a-f were synthesized and evaluated for anticancer activity in vitro in colon (COLO-205, breast (Zr-75-1 and prostate (PC-3 cancer cell lines by MTT assay using adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition 61.2 to 79.2 at 20 mg/ml and 67.2 to 87.2 at 40 mg/ml in PC-3 cell line which is superior to the activity of Adriamycin. In comparison compounds 11d-f were less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to 54.9 at 10 mg/ml concentration while in COLO-205 cell line 11a-f showed poor activity.

  17. Clinical and laboratory assessment of a combination of drugs with radiation. Coordinated programme on improvement in radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Applications were clinically studied of misonidazole (MISO) as a hypoxic cell radiosensitizer with pharmacokinetic studies. Work with desmethylmisonidazole was focused on its penetration into the CNS because its low lipophilicity would predict poorer access than MISO. Laboratory work was focused on the interaction of hyperthermia with drugs. Cytotoxicity of MISO induced by hyperthermia was studied. Heat response following hypoxic pretreatment with MISO of EMT6 spheroids showed marked enhancement of subsequent heat killing dependent on the duration of the hypoxic pretreatment. The effect was studied in vitro of preheat temperature at modest temperatures (39 to 430C) on thermal tolerance and subsequent hyperthermic (43 to 440C) interaction with bleomycin, adriamycin and BCNU. Interaction between several cytotoxic drugs and two potentially critical normal tissues, skin and bone marrow was studied in the mouse. No increase in the heat reaction in the skin of the mouse foot was observed following single injections of adriamycin, bleomycin or 5 daily doses of bleomycin together with a single heat treatment. Single doses of BCNU and CTX increased the heat reaction. The radioprotector WR2721 failed to protect against either the heat or heat drug reactions from CTX and BCNU

  18. Synthesis and functionalization of magnetic nanoparticles with covalently bound electroactive compound doxorubicin

    International Nuclear Information System (INIS)

    We report here on covalent functionalization of magnetic nanoparticle colloidal suspension (ferrofluid) with doxorubicin. Since doxorubicin (adriamycin) is a potent anti-cancer drug, such particles can be guided with external magnetic field to a target tissue, a carrier process that may overcome the non-specificity and efficiency of adriamycin as a drug. The nanoferrite functionalization was effected by means of acid chloride chemistry leading to the formation of covalent bond between the hydroxyl groups at the nanoparticle surface and acid chloride molecules. This procedure can be easily tailored to provide the nanoferrites with various functionalities capable of further modifications with, e.g., drug molecules. Thus, we used such modified nanoferrites to covalently attach molecules of anti-tumor drug-doxorubicin. The attachment was verified by means of FTIR and cyclic voltammetry. Mean size of nanoferrites was evaluated by powder X-ray diffraction (PXRD) technique and high-resolution field emission scanning electron microscope (HR-FESEM). The amount of doxorubicin attached to nanoparticles was assessed by means of quartz crystal microbalance combined with cyclic voltammetry.

  19. Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment

    International Nuclear Information System (INIS)

    RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance

  20. Response to X-radiation and cytotoxic drugs of clonal subpopulations of different ploidy and metastatic potential isolated from RIF-1 mouse sarcoma

    International Nuclear Information System (INIS)

    Clonal subpopulations of different ploidy values and metastatic capacities, isolated from the RIF-1 mouse sarcoma, have been tested for in vitro X-radiation sensitivity, for in vitro sensitivity to adriamycin and for in vitro and in vivo sensitivity to melphalan and CCNU. Following X-radiation, no consistent differences in the survival curve characteristics (Do and n) of diploid, tetraploid and octoploid cells were observed. In addition no relationship between radiation response and metastic capacity was observed. For drug response, no marked differences were found in the dose response curves of RIF-1 clones treated in vitro with adriamycin. However, a wide variation in the responses of RIF-1 clones to in vitro melphalan treatment was observed which was independent of both ploidy and metastatic capacity. Although the responses of RIF-1 clones to in vitro CCNU treatment were similarly independent of metastatic capacity, a clear relationship between CCNU sensitivity and ploidy was observed. Thus, all diploid RIF-1 clones were markedly more sensitive to CCNU treatment than either tetraploid or octoploid RIF-1 clones. For both melphalan and CCNU treatment the relative sensitivities in vitro correlated with in vivo sensitivities as assayed by clonogenic cell survival. (author)

  1. 碱基切除修复基因HOGG1特异性锤头状核酶表达载体的构建及其功能的初步研究%Constructing the Eukaryotic Expression Vector to Study Preliminarily the Functions of Hammerhead Ribozyme Targeting Base Excision Repair Gene HOGG1

    Institute of Scientific and Technical Information of China (English)

    张遵真; 张勤; 吴媚

    2006-01-01

    Objective Adriamycin is widely used as an effective anti-tumor drug clinically treating a number of human cancers, but the effect of adriamycin is limited by drug resistance. The various kinds of investigations indicated that the anti-tumor activity of adriamycin resulted from drug-induced free radical formation. The free radicals could lead to oxidative DNA damage, and the lesion would be repaired by base excision repair (BER) pathway. Human 8-oxoguanine DNA glycosylase 1 (HOGG1) is a key enzyme on BER pathway. To study the influence and biological mechanism of the HOGG1 to adriamycin drug-sensitivity, the eukaryotic expression vector with gene of hammerhead ribozyme targeting HOGG1 mRNA would be constructed and identified, and then the change of drug-sensitivity in lung cancer A549 cells would be investigated. Methods According to computer design, two specific restriction site BamHⅠ and EcoRⅠ were added to both ends of the ribozyme gene, then the modified ribozyme gene was synthesized and cloned into the eukaryotic expression vector pcDNA3.1(+). The positive recombinants were screened by ampicillin resistance, and plasmids were extracted from the positive recombinants and digested by BamH Ⅰ and EcoR Ⅰ, and then were analyzed by agarose gel electrophoresis and DNA sequencing. The recombinants were transiently transfected into A549 cells. The positive recombinants were identified by reverse transcription-polymerase chain reaction (RT-PCR) targeting to NEO gene, which was a neomycin resistance gene for selection of stable cell lines and only existed in vectors. The changes of HOGG1 mRNA in A549 cells were detected by RT-PCR. Then the cellular sensitivity to adriamycin was tested by comparison between untransfected cells and transfected cells by MTT assay. The adriamycin-induced DNA damage was investigated by comet assay or single cell gel electrophoresis (SCGE) between untransfected and transfected cells. Results The recombinants containing the ribozyme gene

  2. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Flampouri, Stella [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Zaiden, Robert [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Slayton, William [Department of Pediatrics, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Sandler, Eric [Department of Pediatrics, Division of Hematology/Oncology Nemours Children' s Clinic, Jacksonville, Florida (United States); Ozdemir, Savas [Department of Radiology, Division of Functional and Molecular Imaging, University of Florida College of Medicine, Jacksonville, Florida (United States); Dang, Nam H.; Lynch, James W. [Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P. [Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida (United States)

    2014-08-01

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on {sup 18}F-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes

  3. A Variant of Human Estrogen Receptor-α, hER-α36 Weakens Docetaxel Drug Efficacy against Human Breast Cancer Cell Line MCF-7

    Institute of Scientific and Technical Information of China (English)

    Li Yu; Peng Shen

    2009-01-01

    Objective: hER-α36 is a variant of estrogen receptor-α, identified and cloned by a team of American. This research is to determine whether hER-α36 can enhance or weaken chemosensitivity to docetaxel in breast cancer cell line MCF-7(ERα66 positive).Methods: RT-PCR was used to detect the expressions of ERα66 and ERα36 in the two human breast cancer cell lines MCF-7(MCF-7/ERα66)and MCF-7 transfected with ERα36(MCF-7/ERα36). The two cell lines were treated with docetaxel(0~100μmol/L), and cell growth and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide) assay (using adriamycin (0~50μmol/L)as the control) and flowcytometry. Western blot analysis was used to measure the effect of docetaxel on phosphor-ERK1/2 expression in the two cell lines.Results: The expressions of ERα36 and ERα66 were detectable in both MCF-7/ERα66 and MCF-7/ERα36 cell lines, while the expression of ERα36 in MCF-7/ER36 cells was higher. Both docetaxel and adriamycin inhibited the proliferation of both cells lines in a dose and time dependent manner. In comparison with MCF-7/ERα36 cell line, the MCF-7/ERα66 cells produced greater growth inhibition and apoptosis after treatment with docetaxel, but there was no significant difference in growth inhibition between the two cell lines treated with adriamycin; The MCF-7/ERα36 cell line resulted in a significant activation (phosphorylation) of ERK1/2 after treatment with docetaxel in a dose-dependent manner, but in the MCF-7/ERα66 cell line , a decrease in the level of phosphor- ERK1/2 expression was observed as the dose of docetaxel increased.Conclusion: ERα36 may be an agent that weakens chemosensitivity to docetaxel in breast cancer, probably by activating the expression of ERK1/2.

  4. Protein arginine methyltransferase 1 may be involved in pregnane x receptor-activated overexpression of multidrug resistance 1 gene during acquired multidrug resistant

    Science.gov (United States)

    Li, Tingting; Kong, Ah-Ng Tony; Ma, Zhiqiang; Liu, Haiyan; Liu, Pinghua; Xiao, Yu; Jiang, Xuehua; Wang, Ling

    2016-01-01

    Purpose Pregnane x receptor (PXR) - activated overexpression of the multidrug resistance 1 (MDR1) gene is an important way for tumor cells to acquire drug resistance. However, the detailed mechanism still remains unclear. In the present study, we aimed to investigate whether protein arginine methyl transferase 1(PRMT1) is involved in PXR - activated overexpression of MDR1 during acquired multidrug resistant. Experimental Design Arginine methyltransferase inhibitor 1 (AMI-1) was used to pharmacologically block PRMT1 in resistant breast cancer cells (MCF7/adr). The mRNA and protein levels of MDR1 were detected by real-time PCR and western blotting analysis. Immunofluorescence microscopy and co-immunoprecipitation were used to investigate the physical interaction between PXR and PRMT1. Then, 136 candidate compounds were screened for PRMT1 inhibitors. Lastly, luciferase reporter gene and nude mice bearing resistant breast cancer xenografts were adopted to investigate the anti-tumor effect of PRMT1 inhibitors when combined with adriamycin. Results AMI-1 significantly suppressed the expression of MDR1 in MCF7/adr cells and increased cells sensitivity of MCF7/adr to adriamycin. Physical interaction between PRMT1 and PXR exists in MCF7/adr cells, which could be disrupted by AMI-1. Those results suggest that PRMT1 may be involved in PXR-activated overexpression of MDR1 in resistant breast cancer cells, and AMI-1 may suppress MDR1 by disrupting the interaction between PRMT1 and PXR. Then, five compounds including rutin, isoquercitrin, salvianolic acid A, naproxen, and felodipline were identified to be PRMT1 inhibitors. Finally, those PRMT1 inhibitors were observed to significantly decrease MDR1 promoter activity in vitro and enhance the antitumor effect of adriamycin in nude mice that bearing resistant breast cancer xenografts. Conclusions PRMT1 may be an important co-activator of PXR in activating MDR1 gene during acquired resistance, and PRMT1 inhibitor combined with

  5. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

    Science.gov (United States)

    Karanovic, Danijela; Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  6. Involved-Node Proton Therapy in Combined Modality Therapy for Hodgkin Lymphoma: Results of a Phase 2 Study

    International Nuclear Information System (INIS)

    Purpose: This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I to III Hodgkin lymphoma (HL) with mediastinal involvement. Methods and Materials: Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis. Results: The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed. Conclusions: Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to

  7. Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1±2.9 x 106/kg (n=10) and 3.1±1.5 x 105/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

  8. Langerhan’s cell sarcoma: two case reports

    Directory of Open Access Journals (Sweden)

    Tasneem A. Kaleem

    2016-04-01

    Full Text Available Langerhan’s cell sarcoma (LCS is a rare neoplasm with a poor prognosis. To our knowledge, only sixty-six cases have been published. We discuss two patients who presented very differently with LCS, as well as a recently published review of all sixty-six cases. Our first case had a complicated history of metastatic, high-grade myxofibrosarcomas and presented with a single skin lesion of LCS which was treated with resection to a positive margin and adjuvant radiotherapy. The LCS recurred locoregionally and was again resected. The patient is alive two years after initial diagnosis. The second case presented with bone marrow and splenic involvement, leukocytosis, and thrombocytopenia. This patient had an excellent response to etoposide, prednisone, oncovorin, cyclophosphamide, and adriamycin, with normalization of the complete blood count, negative bone marrow biopsy at follow up, and splenectomy without viable neoplasm. This patient is alive without signs of disease at 16 months after initial diagnosis.

  9. Enhanced growth medium and method for culturing human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R. (7290 Sayre Dr., Oakland, CA 94611); Smith, Helene S. (5693 Cabot Dr., Oakland, CA 94611); Hackett, Adeline J. (82 Evergreen Dr., Orinda, CA 94563)

    1983-01-01

    Methods are disclosed for isolating and culturing human mammary epithelial cells of both normal and malignant origin. Tissue samples are digested with a mixture including the enzymes collagenase and hyaluronidase to produce clumps of cells substantially free from stroma and other undesired cellular material. Growing the clumps of cells in mass culture in an enriched medium containing particular growth factors allows for active cell proliferation and subculture. Clonal culture having plating efficiencies of up to 40% or greater may be obtained using individual cells derived from the mass culture by plating the cells on appropriate substrates in the enriched media. The clonal growth of cells so obtained is suitable for a quantitative assessment of the cytotoxicity of particular treatment. An exemplary assay for assessing the cytotoxicity of the drug adriamycin is presented.

  10. 组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞增殖影响的动物实验研究%The Effect of Histone Deacetylase Inhibitor Combined with Chemotherapy on Breast Cancer Cells in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    聂建云; 陈杨萍; 黄云超

    2011-01-01

    Objective: To study the effect of histone deacetylase inhibitor SAHA (N-Hydroxy-N- phenyloctanediamide)combined with chemotherapy on breast cancer cells in nude mice.Methods: Breast cancer cell suspension was subcutaneously injected into 80 nude mice to establish breast cancer model When the transplanted tumor was about 10mm in length, 60 mice with tumor in similar size were selected and divided into six groups, with 10 in each group.The six groups were the control group, SAHA group,taxol group, adriamycin group, taxol plus SAHA group, and adriamycin plus SAHA group.Data including blood cell count, serum level of cholesterol, liver function ( serum glutamic-pyruvic transaminase and bilirubin ), kidney function ( serum urea nitrogen and creatinine ), body weight, wet weight of tumor, inhibitory rate and tumor volume were collected.SPSS 12.0 software was used for statistical analysis.Results: Compared with the control group, the treatment groups had higher inhibitory rate and lower tumor volume ( P< 0.05).The taxol plus SAHA group showed superiority in inhibiting tumor growth ( P< 0.05).Compared with the control group,the groups treated with taxol or adriamycin had lower body weigh, lower level of white blood cell count, lower level of serum glutamic-pyruvic transaminase and higher level of bilirubin ( P < 0.05 ).No differences were foumd in the above indices between chemotherapy groups and SAHA plus chemotherapy groups ( P > 0.05 ).Conclusion: SAHA combined with chemotherapy (taxol or adriamycin ) has synergistic inhibitory ettect on the growth of breast cancer in nude mice without increasing side effects, suggesting its possible application in breast cancer treatment in the future.%目的:通过动物模型研究组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞株增殖周期的影响.方法:饲养Balb/c-nu/nu雌性裸鼠,细胞悬液皮下注射法构建人乳腺癌细胞株MCF-7裸鼠移植瘤模型,随机分为6组(对照组、组蛋白去

  11. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial

    DEFF Research Database (Denmark)

    Oakman, C; Francis, P A; Crown, J;

    2013-01-01

    Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-...... statistically supported because of limited numbers. Conclusion With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control....... efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant...

  12. Nasopharyngeal angio-fibroma with intracranial extension: Situating the chemotherapy-radiotherapy association; L'angiofibrome nasopharyngien avec extension intracranienne: place de l'association chimiotherapie-radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Belcadhia, M.; Mania, R.; Harzallah, M.; Bouzouita, K. [CHU Farhat-Hached de Sousse, Service d' ORL et de Chirurgie Cervicofaciale, Sousse (Tunisia); Bouaouina, N. [CHU Farhat-Hached de Sousse, Service de Radiotherapie, Sousse (Tunisia)

    2008-09-15

    Nasopharyngeal angio-fibroma is a locally aggressive, although histologically benign, vascular neoplasm. This neoplasm accounts for 0.05% of head and neck tumours and affects almost exclusively male adolescents. Surgery is considered as the primary treatment of nasopharyngeal angio-fibroma. Other treatment modalities such as radiotherapy and chemotherapy are still recommended for intracranial extension involving the cavernous sinus or the internal carotid artery. We report a rare case of nasopharyngeal angio-fibroma, further complicated with a Kennedy syndrome in a 34 year-old women. The treatment consisted in a chemotherapy (adriamycin, decarbazine) followed by radiotherapy. We discuss the relevance and outcome of the association chemotherapy-radiotherapy in the treatment of nasopharyngeal angio-fibroma with a consistent intracranial extension (stage III B of Arch Otolaryngol Head Neck Surg 122 (2003) 122-129). (authors)

  13. ESR of copper and iron complexes with antitumor and cytotoxic properties

    Energy Technology Data Exchange (ETDEWEB)

    Antholine, W.E.; Kalyanaraman, B.; Petering, D.H.

    1985-12-01

    The relatively few iron and copper metal complexes which have been examined in cells and tissues for their redox properties, radical generation properties, and antitumor activity are discussed for studies which utilized electron spin resonance spectroscopy (ESR). A common property of a number of metal complexes, which include bleomycin, adriamycin, and thiosemicarbazones described in this review, is that they are readily reduced by thiol compounds and oxidized by oxygen or reduced species of oxygen to produce radicals. Structural features of these reactions are identified by ESR spectroscopy in model systems and often in cells. Furthermore, ESR spectroscopy has been most useful to probe the environment of the complexes in cells and to measure the rate of reduction of their oxidized forms. As a result of these studies, it is anticipated that more attention will be given to the exploration of redox-active metal complexes as drugs. 95 references.

  14. Cranial irradiation of children with soft-tissue sarcomas arising in parameningeal sites

    International Nuclear Information System (INIS)

    Soft-tissue sarcomas arising in parameningeal sites are characterized by the potential of a direct meningeal invasion. In order to improve survival rates, a treatment program was started which included whole cranial irradiation with a dose of 24 to 30 Gy and primary tumor irradiation with 55 to 65 Gy, and polychemotherapy with vincristine, actinomycin D and cyclophosphamide, and, in some cases, adriamycin. Results in a series of 9 children treated by this program were compared with a historical group of 12 children without cranial irradiation. In the group with extended irradiation of the brain, survival was 40%, stabilized at the 13th month of treatment, and 38.1% if orbitary tumors were excluded. In the historical group these values were only 20.83% and 15.67%, respectively. The differences were statistically significant. (author). 2 figs., 2 tabs., 23 refs

  15. Caso para diagnóstico Case for diagnosis

    Directory of Open Access Journals (Sweden)

    Cristina Paula Salaro

    2011-08-01

    Full Text Available Paciente do sexo masculino de 55 anos com placas e nódulos infiltrados exuberantes em membro inferior esquerdo há seis meses. Cardiopatia, nefropatia e endocrinopatia associadas. O exame histopatológico, acrescido da imunoistoquímica, confirma linfoma cutâneo difuso de células B. Marcadores CD-20, CD-79a e Ki-67 foram positivos. A quimioterapia com ciclofosfamida, adriamicina e vincristina promoveu remissão parcialA fifty-five year old Caucasian male presented with infiltrated plaques and nodules on the left leg. The lesions had been present for 6 months. He presented associated cardiopathy, nephropathy and endocrinopathy. Histopathological and immunohistochemical examinations confirmed the diagnosis of cutaneous diffuse B cell lymphoma. CD 20, CD 79a and Ki-67 were positive. Chemotherapy with cyclophosphamide, adriamycin and vincristine promoted partial remission

  16. Concurrent Presentation of Hodgkin Lymphoma and Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Rekha Chandran

    2013-01-01

    Full Text Available The simultaneous presentation of the Hodgkin lymphoma and multiple myeloma in the absence of prior chemotherapy or radiation is very rare. Here, we discuss a 72-year-old patient who initially presented with generalized pruritis. Workup led to a diagnosis of multiple myeloma which progressed and required treatment. As part of his pretreatment workup, an MRI was performed to evaluate skeletal lesions. This revealed diffuse and bulky adenopathy which was confirmed by PET. A biopsy of an axillary node was consistent with the nodular sclerosing type Hodgkin lymphoma. He was treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD chemotherapy × 6 resulting in complete resolution of his adenopathy and pruritis as well as improvement in his myeloma.

  17. Combination chemotherapy for advanced diffuse non-Hodgkin's lymphomas in relapse following local radiotherapy

    International Nuclear Information System (INIS)

    Eleven patients with advanced diffuse non-Ho-dgkin's lymphoma arising from head and neck in relapse following local radiotherapy were treated with C-MOPP or Adriamycin-based combination chemotherapy. Eight patients had diffuse lymphoma of large cell type, two diffuse lymphoma of medium-sized cell type and one pleomorphic type of lymphoma. Complete remission was obtained in 8 of 11 patients (72.7 %). Three of these had relapsed within two years after completion of combination chemotherapy; all of three expired at 27 months, 41 months and 48 months, respectively. On the other hand, three patients whose complete remission lasted beyond two years still survive 46 months, 48 months, and 66 months without recurrence. The main side-effects during induction chemotherapy was bone marrow suppression and its related infections. (author)

  18. Radiotherapy to the surviving kidney after unilateral nephrectomy in bilateral Wilms' tumour

    International Nuclear Information System (INIS)

    Four out of seven patients with bilateral tumours died in the period from 1952 to 1960 and five out of eight in the period from 1971 to 1989, at St Bartholomew's Hospital and the Hospital for Sick Children. More aggressive chemotherapy with both adriamycin and actinomycin D and concern over young age being predisposed to late radiation morbidity kept radiotherapy dose prescriptions to the surviving kidney below the quoted renal radiation tolerance dose equivalent. In three long-term survivors treated with daily fractions up to 167 cGy and total doses of 1000-1200 cGy, renal function and growth was within the ''normal'' range at follow-up and the patients normotensive 6-8 years later. As four of the eight patients reported here died from local disease progression within the kidney (albeit despite slightly larger dose prescriptions), the authors discuss the potential for larger total doses to be delivered in this situation. (author)

  19. A Novel Drug Delivery System for Osteosarcoma Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A thermo-responsive chitosan hydrogel system (TRCHS) was prepared by chitosan ( CS ) andβ- glycerophosphate ( β- GP ) to deliver Adriamycin (ADM) locally for curing osteosarcoma . Release property was investigated by release experiments in vitro and results show that it can be applied to local drug release because it is able to release drug at high concentration for 17 days. The treatment effect was studied by injecting intratumorally to osteosarcoma tumors ( CRL- 1427) implanted subcutaneously on Specific Pathogen-free (SPF) mice. The statistical analytical results show that TRCHS delivering ADM is more efficacious than saline intratumoral injection,which loads the same quantity of ADM , but is less poisonous. Based on the analysis above, this novel biodegradable polymer implant is an effective and safe vehicle for sustained local delivery of ADM, and is supposed to be applied in neoadjuvant chemotherapy for osteosarcoma.

  20. Recent results in the treatment of early and late testicular cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seeber, S.; Schuette, J.; Niederle, N.; Schmidt, C.G.

    1983-04-01

    This report summarizes our long-term experience with sequential combination chemotherapy in early and late testicular cancer and presents data from a total of 390 patients treated at the West German Tumor Center Essen between 1973 and 1981. In stage II A (positive retroperitoneal nodes, radically resected) the projected 5-year survival rate is 97%, in stage II B (residual disease after lymphadenectomy), and in stage II C (massive abdominal involvement) the long-term survival was 70% and 30%, respectively. In disseminated disease survival was closely related to the initial tumour burden (> 80% after 5 years for minimal pulmonal disease and < 30% in patients with pulmonal plus massive retroperitoneal involvement). Adriamycin/cisplatinum and belban/bleomycin were equally effective in the total analysis; however, the first combination appeared to be superior in choriocarcinoma, the latter in embryonal carcinoma. An analysis of primary therapeutic failures revealed a low incidence of cross-resistance for the two sequential combinations.

  1. Determination of somatic mutations in human erythrocytes by cytometry

    International Nuclear Information System (INIS)

    Flow cytometric assays of human erythrocytes labeled with monoclonal antibodies specific for glycophorin A were used to enumerate variant cells that appear in peripheral blood as a result of somatic gene-loss mutations in erythrocyte precursor cells. The assay was performed on erythrocytes from 10 oncology patients who had received at least one treatment from radiation or mutagenic chemotherapy at least 3 weeks before being assayed. The patients were suffering from many different malignancies (e.g., breast, renal, bone, colon and lung), and were treated with several different mutagenic therapeutics (e.g., cisplatinum, adriamycin, daunomycin, or cyclophosphamide). The frequency of these variant cells is an indication of the amount of mutagenic damage accumulated in the individual's erythropoietic cell population. Comparing these results to HPRT clonogenic assays, we find similar baseline frequencies of somatic mutation as well as similar correlation with mutagenic exposures. 9 refs., 3 figs., 1 tab

  2. Determination of somatic mutations in human erythrocytes by cytometry

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, R.H.; Langlois, R.G.; Bigbee, W.L.

    1985-06-21

    Flow cytometric assays of human erythrocytes labeled with monoclonal antibodies specific for glycophorin A were used to enumerate variant cells that appear in peripheral blood as a result of somatic gene-loss mutations in erythrocyte precursor cells. The assay was performed on erythrocytes from 10 oncology patients who had received at least one treatment from radiation or mutagenic chemotherapy at least 3 weeks before being assayed. The patients were suffering from many different malignancies (e.g., breast, renal, bone, colon and lung), and were treated with several different mutagenic therapeutics (e.g., cisplatinum, adriamycin, daunomycin, or cyclophosphamide). The frequency of these variant cells is an indication of the amount of mutagenic damage accumulated in the individual's erythropoietic cell population. Comparing these results to HPRT clonogenic assays, we find similar baseline frequencies of somatic mutation as well as similar correlation with mutagenic exposures. 9 refs., 3 figs., 1 tab.

  3. Ewing Sarcoma of the External Ear Canal.

    Science.gov (United States)

    Binnetoglu, Adem; Baglam, Tekin; Tokuc, Gulnur; Kecelioglu Binnetoglu, Kiymet; Gerin, Fatma; Sari, Murat

    2016-01-01

    Background. Ewing sarcoma (ES) is a high-grade malignant tumor that has skeletal and extraskeletal forms and consists of small round cells. In the head and neck region, reported localization of extraskeletal ES includes the larynx, thyroid gland, submandibular gland, nasal fossa, pharynx, skin, and parotid gland, but not the external ear canal. Methods. We present the unique case of a 2-year-old boy with extraskeletal ES arising from the external ear canal, mimicking auricular hematoma. Results. Surgery was performed and a VAC/IE (vincristine, adriamycin, cyclophosphamide alternating with ifosfamide, and etoposide) regimen was used for adjuvant chemotherapy for 12 months. Conclusion. The clinician should consider extraskeletal ES when diagnosing tumors localized in the head and neck region because it may be manifested by a nonspecific clinical picture mimicking common otorhinolaryngologic disorders. PMID:27313930

  4. 20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

    Science.gov (United States)

    Liu, Junhua; Wang, Xu; Liu, Peng; Deng, Rongxin; Lei, Min; Chen, Wantao; Hu, Lihong

    2013-07-15

    Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. PMID:23683834

  5. Non-alkaloids extract from Stemona sessilifolia enhances the activity of chemotherapeutic agents through P-glycoprotein-mediated multidrug-resistant cancer cells.

    Science.gov (United States)

    Han, Lu; Ma, Yang-Mei; An, Li; Zhang, Qiao; Wang, Chang-Li; Zhao, Qing-Chun

    2016-01-01

    One of the major impediments to the successful treatment of cancer is the development of resistant cancer cells, which could cause multidrug resistance (MDR), and overexpression of ABCB1/P-glycoprotein (P-gp) is one of the most common causes of MDR in cancer cells. Recently, natural products or plant-derived chemicals have been investigated more and more widely as potential multidrug-resistant (MDR) reversing agents. The current study demonstrated for the first time that non-alkaloids extract from Stemona sessilifolia significantly reversed the resistance of chemotherapeutic agents, adriamycin, paclitaxel and vincristine to MCF-7/ADR cells compared with MCF-7/S cells in a dose-dependent manner. The results obtained from these studies indicated that the non-alkaloids extract from S. sessilifolia plays an important role in reversing MDR of cancer as a P-gp modulator in vitro and may be effective in the treatment of multidrug-resistant cancers. PMID:26190165

  6. Effect of Human WEE1 and Stem Cell Factor on Human CD34+ Umbilical Cord Blood Cell Damage Induced by Chemotherapeutic Agents

    Institute of Scientific and Technical Information of China (English)

    Ping LEI; Yong HE; Wenfang SHI; Jilin PENG; Sha WU; Huifen ZHU; Jianguo CHEN; Guanxin SHEN

    2007-01-01

    Myelosuppression is one of the major side-effects of most anticancer drugs. To achieve myeloprotection, one bicistronic vector encoding anti-apoptotic protein human WEE1 (WEE1Hu) and proliferation-stimulating stem cell factor (SCF) was generated. In this study, we selected human umbilical cord blood CD34+ cells as the in vitro model in an attempt to investigate whether WEE1Hu, rather than conventional drug-resistant genes, can be introduced to rescue cells from the damage by chemotherapeutic agents such as cisplatin, adriamycin, mitomycin-c and 5-fluorouracil. Cell viability and cytotoxicity assay,colony-forming units in culture assay and externalization of phospholipid phosphatidylserine analysis showed that the expression of WEE1Hu and SCF in CD34+ cells provided the cells with some protection. These findings suggest that the expression of WEE1Hu and SCF might rescue CD34+ cells from chemotherapyinduced myelosuppression.

  7. Experimental basis for the combination of irradiation with cytotoxic drugs

    International Nuclear Information System (INIS)

    For the treatment of therapy resistant tumours the combination of irradiation with chemical substances, especially cytotoxic drugs, can have advantages. In order to obtain supraadditive effects it is reasonable to know the mechanism of interaction. In this respect interactions are very important on the level of intracellular recovery processes, of repopulation, and of hypoxic cells. Substances have been discussed which interact with ionizing radiation on these levels. Especially the modification of recovery processes can increase the radiation effects efficiently. In this connection substances like actinomycin D, bleomycin, adriamycin, and newer drugs like aclacinomycin are of interest. For such a treatment tumours with a high capacity of recovery must be considered. An individual selection would have great advantages therefore. (orig.)

  8. Comparison of the oncogenic potential of several chemotherapeutic agents

    International Nuclear Information System (INIS)

    Several chemotherapeutic drugs that have been routinely used in cancer treatment were tested for their carcinogenic potential. Two antitumor antibiotics (adriamycin and vincristine), an alkalating agent (melphalan), 5-azacytidine and the bifunctional agent cis-platinum that mimics alkylating agents and/or binds Oxygen-6 or Nitrogen-7 atoms of quanine were tested. Cell killing and cancer induction was assessed using in vitro transformation system. C3H/10T 1/2 cells, while normally exhibiting contact inhibition, can undergo transformation from normal contact inhibited cells to tumorgenic cells when exposed to chemical carcinogens. These cells have been used in the past by this laboratory to study oncogenic transformation of cells exposed to ionizing radiation and electron affinic compounds that sensitize hypoxic cells to x-rays. The endpoints of cell killing and oncogenic transformation presented here give an estimate of the carcinogenic potential of these agents

  9. Primary cardiac lymphoma: diagnostic tools and treatment challenges.

    LENUS (Irish Health Repository)

    Bambury, R

    2011-03-01

    Primary cardiac lymphoma (PCL) is a rare malignancy and the optimal treatment strategy remains uncertain. It appears to respond much better to systemic chemotherapy than to surgery and it should be considered in the differential diagnosis of all cardiac tumours before definitive management is undertaken. We report a case of this rare disorder treated successfully with a combination of rituximab and cyclophosphamide, adriamycin, vincristine and prednisolone. The patient developed recurrent unstable ventricular tachycardia (VT) post-chemotherapy secondary to extensive scarring at the tumour site. The tumour as well as the post-treatment scarring is well illustrated by cardiac magnetic resonance imaging highlighting its usefulness in this setting. An implantable cardioverter defibrillator (ICD) was placed. This is only the second case in the literature of PCL to have an ICD placed for recurrent VT. A brief literature review is included.

  10. Successful Chemotherapy on a Pregnant Non-Hodgkin's Lymphoma Patient

    Directory of Open Access Journals (Sweden)

    Toki,Hironobu

    1990-12-01

    Full Text Available We report a case of a non-Hodgkin's lymphoma (NHL patient treated successfully with combination chemotherapy during pregnancy who delivered a full-term baby. A 29 year-old patient with cervical and inguinal lymphadenopathy in the 27th week of gestation was referred to our hospital. The diagnosis of lymph node biopsy was NHL (diffuse, large cell type with B-cell phenotype. Three courses of CHOP regimen (adriamycin, cyclophosphamide, vincristine and prednisolone were given before delivery. The patient has been in complete remission for three years and her baby has been in normal development. Our case supports previous reports that chemotherapy in the third trimester may be given safely on NHL patients.

  11. Recurrent rhabdoid meningioma with lymph node, pulmonary and bone metastases: a diagnostic and therapeutic challenge.

    Science.gov (United States)

    Kakkar, Aanchal; Baghmar, Saphalta; Garg, Ajay; Suri, Vaishali; Raina, Vinod; Sarkar, Chitra; Sharma, Mehar Chand

    2016-07-01

    Rhabdoid meningioma is a rare meningioma variant, classified as WHO grade III. Although this tumor is known for its aggressive behavior and poor prognosis, extracranial metastasis is rare. We report the rare case of a 31-year-old patient with rhabdoid meningioma which recurred several times despite gross total resection, radiation therapy, and gamma knife radiosurgery, and the last recurrence was associated with metastases to lungs, lymph node and bone. The patient showed no response to paclitaxel-carboplatin, or vincristine-cyclophosphamide-adriamycin chemotherapy, and succumbed to the disease. Metastases from rhabdoid meningioma prove to be a diagnostic challenge, and treatment for metastatic meningiomas is not optimized, thus necessitating documentation and interdisciplinary consensus on management protocols. PMID:26875176

  12. Dento-maxillofacial abnormalities caused by radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Cheol Woo; Hwang, Eui Hwang; Lee, Sang Rae [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Kyunghee University, Seoul (Korea, Republic of)

    2000-12-15

    A case of dento-maxillofacial abnormality involving a 10-year-old male patient with a history of esthesioneuroblastoma is presented. This patient had been treated with 54 Gy {sup 60}Co-gamma-radiation to the nasal cavity for 6 weeks and 6 cycles of combination chemotherapy of Cyclophosphamide, Cisplatin, Adriamycin, VM-26 (Teniposide), and DTIC (Dacarbazine) when he was 16 months of age. Five years after cessation of cancer therapy, he was disease free and transferred for extensive dental care to Kyung Hee University Dental Hospital. A clinical and radiologic follow-up over last 4 years showed root stunting, premature closure of the root apices, microdontia, developmental arrest, small crowns, and partial anodontia. Maxillofacial morphology evaluated by cephalometric analysis showed deficiency of maxillary development.

  13. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  14. Microencapsulation of chemotherapeutic agents

    International Nuclear Information System (INIS)

    Mixing various amounts of chemotherapeutic agents such as cisplatinum, 5-fluorouracil, mitomycin-C, and adriamycin with polymers such as poly-d, 1-lactide, ethylhydroxyethylcellulose, and polycaprolactone, several kinds of microcapsules were made. Among them, microcapsule made from ethylhydroxyethylcellulose showed best yield. Under light microscopy, the capsules were observed as particles with refractive properties. For the basic toxicity test, intraarterial administration of cisplatinum was done in 6 adult mongrel dogs. Follow-up angiography was accomplished in 2 wk intervals for 6 wks. Despite no significant difference in the histopathological examination between the embolized and normal kidneys, follow-up angiogram showed atrophy of renal cortex and diminished numbers of arterial branches in the embolized kidneys. In order to identify the structural properties of microcapsules, and to determine the drug content and the rate of release, further experiment is thought to be necessary. (Author)

  15. Multimodality treatment by radiation and hyperthermochemotherapy for pulmonary and pleural metastases of breast cancers

    Energy Technology Data Exchange (ETDEWEB)

    Endou, Masaru; Suzuki, Hirotoshi; Nakashima, Yukihiro (St. Marianna Univ., Kawasaki (Japan). School of Medicine) (and others)

    1992-06-01

    We treated 17 patients with metastatic pulmonary and pleural breast cancer by a combination of radiation, chemotherapy and hyperthermia. Hyperthermia with chemotherapy using adriamycin, farmorubicin, mitomycin C, 5-fluorouracil, tegafur and/or cisplatin in the form of continuous intravenous infusion was given. The thermochemotherapy had only a limited effectiveness. But good responses are seen in postirradiation adjuvant thermochemotherapy. Heating could alleviate some chemotherapeutic side effects in some way by heat reservoir. Fifty percent survival period was 12 months by the Kaplan-Meier method. As severe or serious side effects were not experienced, this treatment was thought available for outpatients. We believe that multimodality treatment by thermochemotherapy with radiation is promising for advanced or recurrent pulmonary metastases of breast cancers. (author).

  16. Improved tumour response by laser light treatment

    Science.gov (United States)

    Graschew, Georgi; Smith, Janice; Rakowsky, Stefan; Roelofs, Theo A.; Schlag, Peter M.; Stein, Ulrike

    2008-04-01

    Multidrug resistance (MDR) poses a serious barrier to the efficacy of clinical treatment of human cancers with chemotherapeutic drugs. This barrier might be reduced and eventually overcome by the simultaneous application of two or more treatment modalities. This study reports on the synergetic effect of combined application of laser light and cytostatic drugs to induce an improved tumour response in MDR cancer cells. The MDR breast cancer cell line MaTu/ADR, resistant to the drug adriamycin (ADR), was treated with a combination of ADR (125-1000 ng/ml) and laser light (488 nm with a total light dose between 6-18 J/cm2). This combined treatment leads to an additional reduction of the cell vitality by a factor of 2-3 as compared to treatment with ADR alone, suggesting that combined application of laser light and other treatment modalities might constitute a promising strategy for improvements in the tumour response.

  17. Dactinomycin potentiation of radiation pneumonitis: A forgotten interaction

    International Nuclear Information System (INIS)

    No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. The authors experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases. 20 references

  18. Experimental models used for the study of antihepatotoxic agents

    Institute of Scientific and Technical Information of China (English)

    Feroz Ahmad; Nahida Tabassum

    2012-01-01

    Both in vitro and in vivo liver models have been developed in the past years to study the hepatoprotective agents. These systems measure the ability of the test drug to prevent or cure liver toxicity (induced by various hepatotoxins) in experimental animals. In in vitro models fresh hepatocytes are treated with hepatotoxin and the effect of the test drug on the same is evaluated. In in vivo models, a toxic dose or repeated doses of a known hepatotoxin are administered to induce liver damage in experimental animals. The test substance is administered along with, prior to and/or after the toxin treatment. Various chemical agents normally used to induce hepatotoxicty in experimental animals for the evaluation of hepatoprotective agents include carbon tetrachloride, paracetamol, Acrylamide, adriamycin, alcohol, antitubercular drugs etc. The present article explains the mechanism of action of various hepatotoxic chemical/drugs, their dosage and route of administration.

  19. Effect of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer. Methods: 1993-1998 years, Thirty four patients with liver metastasis from breast cancer had received epi-adriamycin, cisplatin, mitomycin and 5-fluorouracil by intrahepatic arterial infusion chemotherapy. Twelve patients had received embolization. Results: Six patients (17.65%) had a complete response, 12 patients (35.29%) had a partial response. The overall response rate was 52.94%. Cumulative survival rates at 1, 2, 3 and 4 years were 56.90%, 25.00%, 5.00% and 5.00% respectively (Kaplan-Meier method). The median overall survival time was 11.5 months. Conclusion: Intra-hepatic arterial infusion chemotherapy is safe and effective for liver metastasis from breast cancer and should be the first choice of treatment for these patients

  20. Design, synthesis and evaluation of Novel 1-(Substituted Acetyl-4-(10-Bromo-8-Chloro-5,6-Dihydro-11H-Benzo[5,6]Cyclohepta[1,2-B]Pyridine-11-Ylidenepiperidines as antitumor agents and farnesyl protein transferase inhibitors

    Directory of Open Access Journals (Sweden)

    Gatne P

    2010-01-01

    Full Text Available Eight novel 1-(substituted acetyl-4-(10-bromo-8-chloro-5,6-dihydro-11H-benzo[5,6] cyclohepta [1,2-b] pyridine-11-ylidenepiperidines were designed by incorporating zinc binding groups to enhance activity. The designed molecules were synthesized and were evaluated for antitumor activity in vitro in five cell lines and for farnesyl protein transferase inhibition. Test compounds (6a-h exhibited antitumor activity in most of the cell lines but were less potent than adriamycin. Compound 6e was most active with IC 50 values of <15 μM in two cell lines tested. Test compounds also exhibited potent FPT inhibitory activity and 6c was most potent with IC 50 value of <30 μM.

  1. Combined modality treatment in fractionated schedules on the RIF-1 tumour

    International Nuclear Information System (INIS)

    A series of experiments was started to test several fractionation schedules of combined radiation and drug treatment. In combination with X-irradiation the following drugs were tested: actinomycin-D, adriamycin, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, Cis-diamminedichloro Platinum II (Cis-Pt) and cyclophosphamide. The endpoint was tumour growth delay, i.e., the number of days required for each tumour in the treated group to grow to 4x its volume on the day of treatment, diminished by the mean value for the untreated control group. The expected value for the combination was calculated by simple addition of the values for each modality alone, since both showed a linear dose-effect relationship. (Auth.)

  2. Experimental Study of Ultrasound on MDR in a Human Tumor in Vivo

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To evaluate the potential efficacy of low-intensity ultrasound (US) in combination with anticancer drugs to reverse multidrug resistance (MDR)in nude mice.METHODS A total of 40 male and female athymic nude mice were inoculated subcutaneously with 5×106 HepG2/ADM and HepG2 cells. Ultrasound with pulsed irradiation at an average intensity of 0.5 W/cm2 was given to the tumor area 10 min after administration of adriamycin (ADM). The tumor 3 dimensional diameters were measured by calipers before and after treatment,and the tumor growth indexes (TGI) calculated. RT-PCR was used to detect the gene levels of the HepG2/ADM cells. Immunohistochemical analyses for MDR proteins were conducted on the tumor tissues.RESULTS The ultrasonic treatment resulted in an average reduction in the tumor volume of 62% one month later. The relative mRNA levels of MDR1 and MRP were significantly different among the following 4 groups:untreated group as control, ADM treated; US treated; and ADM plus US treated. The mRNA levels of mdr1 and mrp were down-regulated in the US groups compared to those of the non-ultrasound groups by multiple comparisons. The relative mRNA levels of Irp expression were not significantly changed. The results of immunohistochemistry indicated that tumor tissue from animals treated with US had remarkably low mdr1 and mrp expression.CONCLUSION The results showed that low-intensity US can effectively reduce the size of adriamycin-resistant human hepotacarcinoma in a nude mouse model, and support the efficacy of US to overcome multiple mechanisms of drug resistance.

  3. Multi-modality treatment of primary nonresectable intrahepatic cholangiocarcinoma with 131I anti-CEA--a Radiation Therapy Oncology Group Study

    International Nuclear Information System (INIS)

    Thirty-seven patients with primary nonresectable intrahepatic cholangiocarcinoma (57% with prior treatment and/or metastasis) were prospectively treated with external radiation, chemotherapy, and 131I labelled anti-CEA. Therapy began in all trials with whole liver irradiation (21.0 Gy, 3.0 Gy/Fx, 4 days/week, 10 MV photons) with alternate treatment day chemotherapy (Adriamycin, 15 mg + 5-FU, 500 mg). One month after external beam therapy, chemotherapy was given (Adriamycin, 15 mg + 5-FU, 500 mg) followed the next day by the first administration of 131I anti-CEA. The treatment schedule used was 20 mCi day 0; 10 mCi day 5 as an outpatient. This schedule was derived from tumor dose estimates which indicated that 20 mCi (8-10 mCi/mg IgG) was sufficient to achieve tumor saturation with a tumor effective half-life of 3 to 5 days, depending upon the species of animal from which the antibody was obtained. The median tumor dose for the 20 mCi + 10 mCi regimen was 6.2 Gy. Antibody therapy was delivered in 2-month cycles using antibody generated in different species of animals; rabbit, pig, monkey, and bovine. Toxicity was limited to hematologic toxicity and was manifested as thrombocytopenia and leukocytopenia (3.2% Grade IV for each according to RTOG toxicity criteria). Tumor remission evaluated by CT scan digitized tumor volume analysis indicated a 26.6% partial response (PR). Tumor remission by physical examination indicated a 33.3% remission rate (25.9% PR and 7.4% complete remission (CR]. The median survival for patients who responded was 15.2 months. The actuarial median survival for the entire group of patients (metastases and previous treatment) was 6.5 months. The longest partial remission is presently more than 4 years

  4. Multi-modality treatment of primary nonresectable intrahepatic cholangiocarcinoma with /sup 131/I anti-CEA--a Radiation Therapy Oncology Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Stillwagon, G.B.; Order, S.E.; Klein, J.L.; Leichner, P.K.; Leibel, S.A.; Siegelman, S.S.; Fishman, E.K.; Ettinger, D.S.; Haulk, T.; Kopher, K.

    1987-05-01

    Thirty-seven patients with primary nonresectable intrahepatic cholangiocarcinoma (57% with prior treatment and/or metastasis) were prospectively treated with external radiation, chemotherapy, and /sup 131/I labelled anti-CEA. Therapy began in all trials with whole liver irradiation (21.0 Gy, 3.0 Gy/Fx, 4 days/week, 10 MV photons) with alternate treatment day chemotherapy (Adriamycin, 15 mg + 5-FU, 500 mg). One month after external beam therapy, chemotherapy was given (Adriamycin, 15 mg + 5-FU, 500 mg) followed the next day by the first administration of /sup 131/I anti-CEA. The treatment schedule used was 20 mCi day 0; 10 mCi day 5 as an outpatient. This schedule was derived from tumor dose estimates which indicated that 20 mCi (8-10 mCi/mg IgG) was sufficient to achieve tumor saturation with a tumor effective half-life of 3 to 5 days, depending upon the species of animal from which the antibody was obtained. The median tumor dose for the 20 mCi + 10 mCi regimen was 6.2 Gy. Antibody therapy was delivered in 2-month cycles using antibody generated in different species of animals; rabbit, pig, monkey, and bovine. Toxicity was limited to hematologic toxicity and was manifested as thrombocytopenia and leukocytopenia (3.2% Grade IV for each according to RTOG toxicity criteria). Tumor remission evaluated by CT scan digitized tumor volume analysis indicated a 26.6% partial response (PR). Tumor remission by physical examination indicated a 33.3% remission rate (25.9% PR and 7.4% complete remission (CR). The median survival for patients who responded was 15.2 months. The actuarial median survival for the entire group of patients (metastases and previous treatment) was 6.5 months. The longest partial remission is presently more than 4 years.

  5. Interactions of black cohosh, a traditional herbal medicine, with therapy for breast cancer

    International Nuclear Information System (INIS)

    Herbal medicines based on extracts of Cimicifuga racemosa (black cohosh) are widely used by breast cancer patients, but the effects of these extracts have not been rigorously studied. We examined the effects of standardized commercial extracts of black cohosh on the cytotoxicity of radiation, Adriamycin, Taxotere, and Cisplatin to breast cancer cells in vitro. Exponentially growing cultures of EMT6 mouse mammary tumor cells were exposed to black cohosh extracts continuously for 24 h, beginning 4 hours before irradiation or the 2 h drug treatment. Full dose-response curves were determined for radiation and for each drug under three conditions: alone, in combination with black cohosh extract, and in combination with the vehicle used to prepare the extract. Cell survival was assayed using a colony formation assay. The herbal extracts alone had no significant effect on the growth or viability of these breast cancer cells. The effects of the extracts on the outcome of treatment varied with the treatment agent. Black cohosh protected cells slightly from Cisplatin, had no effect on the dose-response curve for radiation, and sensitized cells to Adriamycin and Taxotere. The vehicle had no discernable effect. These findings show that black cohosh extracts are not simply 'harmless herbs' that can be ignored by physicians treating cancer patients, but instead contain active agents which can modulate the effects of therapy with conventional therapeutic agents. Further cell culture studies are needed to determine the mechanism underlying this effect. Studies with tumors and normal tissues in mice are needed to assess whether black cohosh extracts alter the effectiveness of radiation and drugs in treating breast cancer or alter the toxicities of these therapies

  6. Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent)

    International Nuclear Information System (INIS)

    The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of 99mTc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of 99mTc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 μg/ml of tea polyphenol respectively. The uptake of 99mTc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 μM of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment

  7. Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent)

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Aizhi E-mail: zhuaizhi@263.net; Wang Xiangyun; Guo Zhenquan

    2001-08-01

    The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp) and study the effect and mechanism of tea polyphenol (TP) in reversion of multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was used for qualitative detection of Pgp. A comparative study of cytotoxicity and multidrug resistance reversion effect was made by MTT assay for tea polyphenol and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance reversion effect and mechanism were studied by measuring the uptake of {sup 99m}Tc-tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr cells was found to be strong positive, while the Pgp expression of MCF-7 was negative. (2) Although both tea polyphenol and quinidine could not remarkably change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was 3 and 10 respectively. (3) The cellular uptake of {sup 99m}Tc-tetrofosmin was remarkably lower in MCF-7/Adr than in MCF-7. The uptake of {sup 99m}Tc-tetrofosmin in MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500 {mu}g/ml of tea polyphenol respectively. The uptake of {sup 99m}Tc-tetrofosmin in MCF-7/Adr exhibited only a 4-fold increase in the presence of 200 {mu}M of quinidine. Immunocytochemistry can detect P-glycoprotein expression level qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a multidrug resistant modulator similar to quinidine. The multidrug resistance reversion mechanism of tea polyphenol seems to be its inhibition of the activity of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor treatment.

  8. Ultrasonic spectrum analysis for in vivo characterization of tumor microstructural changes in the evaluation of tumor response to chemotherapy using diagnostic ultrasound

    International Nuclear Information System (INIS)

    There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The purpose of this study was to determine the feasibility of ultrasonic spectral analysis for the in vivo characterization of changes in tumor microstructure in the evaluation of tumor response to chemotherapy using diagnostic ultrasound. Experiments were approved by the regional animal care committee. Twenty-four MCF-7 breast cancer bearing nude mice were treated with adriamycin or sterile saline administered by intraperitoneal injection. Ultrasonic radio-frequency (RF) data was collected using a clinically available ultrasound scanner (6-MHz linear transducer). Linear regression parameters (spectral slope and midband-fit) regarding the calibrated power spectra from the RF signals were tested to monitor tumor response to treatment. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for assessment of the density of tumor cell nuclei. Treatment with adriamycin significantly reduced tumor growth in comparison with the control group (p = 0.003). Significant changes were observed in the ultrasonic parameters of the treated relative to the untreated tumors (p < 0.05). The spectral slope increased by 48.5%, from −10.66 ± 2.96 to −5.49 ± 2.69; the midband-fit increased by 12.8%, from −57.10 ± 7.68 to −49.81 ± 5.40. Treated tumors were associated with a significant decrease in the density of tumor cell nuclei as compared with control tumors (p < 0.001). Ultrasonic spectral analysis can detect changes in tumor microstructure after chemotherapy, and this will be helpful in the early evaluation tumor response to chemotherapy

  9. Overexpression of Bax induces apoptosis and enhances drug sensitivity of hepatocellular cancer-9204 cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Zheng; Guang-Shun Yang; Wei-Zhong Wang; Jiang Li; Kai-Zong Li; Wen-Xian Guan; Wen-Liang Wang

    2005-01-01

    AIM: To investigate the role of overexpression of Bax in apoptotic pathways and the response of human hepatocellular cancer (HCC)-9204 cells to cell death induced by adriamycin.METHODS: The whole length of Bax cDNA was transfectrd into human HCC-9204 cells by the method of lipofectamine transfection. An inducible MT-Ⅱ regulatory system was constructed, which allowed controlled expression of protein upon addition of ZnSO4 (100 μmol/L) as an external inducer. Stable transfecting inducible expression vector containing Bax gene was performed. Expression of Bax in protein was analyzed by immunohistochemistry and Western blotting. TUNEL and flow cytometry were used to assess the effect of Bax on apoptosis. Colony assay and tetrazolium blue (MTT) assay were used to evaluate the difference in drug sensitivity of HCC-9204 cells after Bax-transfection.RESULTS: Immunohistochemistry and Western blotting demonstrated that the expression of Bax protein markedly increased in Bax-transfected cells 4 h after the addition cytoplasm and perinuclear region of HCC-9404 cells, and there was ectopic expression in cells with marked condensation of chromatin and cytoplasm (apoptotic cells). Apoptotic index significantly increased in Bax-transfected HCC-9204/Bax cells (3.6 vs 27.2, 4.2 vs 32.3, P<0.05).Flow cytometry analysis showed a significant sub-G1 peak and apoptosis in 15.4% HCC-9204/Bax cells 24 h after treatment. Furthermore, colony survival rate decreased from 66% (HCC-9204/pMD) to 45% (HCC-9204/Bax) 2 dafter ADR withdrawal. MTT assay result showed that the effects of Bax on cell viability following ADR exposure were significant as compared to the vehicle-transfected HCC-9204/pMD cells (21% vs 44%, P<0.01).CONCLUSION: Overexpression of Bax not only induces apoptosis, but also sensitizes HCC-9204 cells to cell death induced by adriamycin.

  10. [Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

    Science.gov (United States)

    Ohta, M; Hara, N; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

    1988-06-01

    We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy. PMID:2454615

  11. Nephroprotective effect of heparanase in experimental nephrotic syndrome.

    Directory of Open Access Journals (Sweden)

    Suheir Assady

    Full Text Available Heparanase, an endoglycosidase that cleaves heparan sulfate (HS, is involved in various biologic processes. Recently, an association between heparanase and glomerular injury was suggested. The present study examines the involvement of heparanase in the pathogenesis of Adriamycin-induced nephrotic syndrome (ADR-NS in a mouse model.BALB/c wild-type (wt mice and heparanase overexpressing transgenic mice (hpa-TG were tail-vein injected with either Adriamycin (ADR, 10 mg/kg or vehicle. Albuminuria was investigated at days 0, 7, and 14 thereafter. Mice were sacrificed at day 15, and kidneys were harvested for various analyses: structure and ultrastructure alterations, podocyte proteins expression, and heparanase enzymatic activity.ADR-injected wt mice developed severe albuminuria, while ADR-hpa-TG mice showed only a mild elevation in urinary albumin excretion. In parallel, light microscopy of stained cross sections of kidneys from ADR-injected wt mice, but not hpa-TG mice, showed mild to severe glomerular and tubular damage. Western blot and immunofluorescence analyses revealed significant reduction in nephrin and podocin protein expression in ADR-wt mice, but not in ADR-hpa-TG mice. These results were substantiated by electron-microscopy findings showing massive foot process effacement in injected ADR-wt mice, in contrast to largely preserved integrity of podocyte architecture in ADR-hpa-TG mice.Our results suggest that heparanase may play a nephroprotective role in ADR-NS, most likely independently of HS degradation. Moreover, hpa-TG mice comprise an invaluable in vivo platform to investigate the interplay between heparanase and glomerular injury.

  12. Clinical evaluation of multimodal treatment for squamous cell carcinoma of the maxillary sinus

    International Nuclear Information System (INIS)

    Seventy-seven patients with squamous cell carcinoma of the maxillary sinus were treated with radiotherapy and surgery (with or without intra-arterial infusion chemotherapy) from 1969 to 1986 at Tokyo Women's Medical College. The treatment given to the subjects was broadly separated into three categories: Treatment I (1969-1974), Treatment II (1975-1977), and Treatment III (1978-1986). Treatment I consisted of surgery and radiotherapy; Treatment II consisted of multimodal treatment by surgery and radiotherapy with 5-FU intra-arterial infusion chemotherapy (IAIC) from the superficial temporal artery; Treatment III consisted of surgery and radiotherapy with Adriamycin IAIC replacing 5-FU IAIC. Radiotherapy involved a total dose of 60 Gy/6 weeks in Treatment I as the standard, 50 Gy/5 weeks with 5-FU (250 mgx20 times/4 weeks) in Treatment III. Surgery by antrotomy was performed before radiotherapy and IAIC, and Denker's operation was done after radiotherapy with IAIC. The influence of patients' age, sex, T stage and N stage were examined as prognostic factors and no statistically significant differences were seen among each treatment periods. The 2-year control rate was 29% in period I, 27% in period II, and 58% in period III. The 5-year cumulative survival rate was 13% for period I, 40% for period II, and 54% for period III; the incidence of side effects during radiotherapy did not appear to increase, and the severity was at a tolerable level considering the results. However, late complications were seen in 6 cases (cataract, 5; obstinate sinusitis, 1). Thus, the study indicates that multimodal treatment using Adriamycin IAIC can minimize face deformity and allows effective function-saving treatment for carcinoma of the maxillary sinus. (author)

  13. Design of parallel microfluidic gradient-generating networks for studying cellular response to chemical stimuli

    Institute of Scientific and Technical Information of China (English)

    Lihui WANG; Dayu LIU; Bo WANG; Jie SUN; Lianhong LI

    2008-01-01

    A microfluidic chip featuring laminar flow-based parallel gradient-generating networks was designed and fabricated. The microchip contains 5 gradient genera-tors and 30 cell chambers where the resulting concentra-tion gradients of drugs are delivered to stimulate on-chip cultured cells. The microfluidics exploits the advantage of lab-on-a-chip technology by integrating the generation of drug concentration gradients and a series of cell opera-tions including seeding, culture, stimulation and staining into a chip. The microfluidic network was patterned on a glass wafer, which was further bonded to a PDMS film. A series of weir structures were fabricated on the cell culture reservoir to facilitate cell positioning and seeding. Cell injection and fluid delivery were controlled by a syringe pump. Steady parallel concentration gradients were gen-erated by flowing two fluids in each network. Over time observation shows that the microchip was suitable for cell seeding and culture. The microchip described above was applied in studying the role of reduced glutathione (GSH) in mediating chemotherapy sensitivity of MCF-7 cells. MCF-7 cells were treated with concentration gradients of As2O3 and N-acetyl cysteine (NAC) for GSH modu-lation, followed by exposure to adriamycin. GSH levels were down-regulated upon As203 treatment and up-regu-lated upon NAC treatment. Suppression of intracellular GSH by treatment with As2O3 has been shown to increase sensitivity to adriamycin. Conversely, elevation of intra-cellular GSH by treatment with NAC leads to increased drug resistance. The integrated microfluidic chip is able to perform multiparametric pharmacological profiling with easy operation, and thus holds great potential for extra-polation to the cell based high-content drug screening.

  14. Radiation dose selection in Hodgkin's disease patients with large mediastinal adenopathy treated with combined modality therapy

    International Nuclear Information System (INIS)

    whom gallium was not done after chemotherapy (p = 0.066). Additionally, patients receiving adriamycin-based chemotherapy regimens had improved outcomes compared to those not receiving adriamycin (p = 0.03.) Conclusions: These retrospective data suggest that low-dose radiotherapy following CR achieved with induction chemotherapy (particularly when documented with gallium scanning) may be as effective as higher doses for bulky HD at presentation. Phase III trials are necessary for confirmation of this hypothesis

  15. Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma

    International Nuclear Information System (INIS)

    Purpose: To examine the long-term effects of treatment in children receiving radiotherapy for head and neck rhabdomyosarcoma. Methods: From 1967 to 1994, a total of 30 children with head and neck rhabdomyosarcoma received megavoltage radiotherapy at one institution. Seventeen patients (57%) have survived and have at least a 5-year follow-up. There were 11 males and 6 females, with a median age of 5.7 years (range 2.2-11.6) at the time of radiotherapy. Tumor location was orbit in 6 patients, infratemporal fossa in 4, paranasal sinuses in 2, and supraglottic larynx in 2; the nasopharynx, pterygopalatine fossa, and parotid gland were sites for the remaining children. All but 2 patients had tumors of embryonal histology. The Intergroup Rhabdomyosarcoma Study (IRS) Group was I in 2, II in 3, and III in 11 children; 1 patient had a recurrent tumor after surgery alone. Radiotherapy volume was the primary tumor or tumor bed in 13, tumor and whole brain in 3, and tumor and craniospinal axis in 1. Median radiotherapy dose to the primary site was 5,040 cGy (range 4,140-6,500) and to the whole brain was 3,000 cGy. All but 1 were treated with 150-200-cGy fractions; 1 patient received 250-cGy fractions for a tumor in the larynx. Chemotherapy was vincristine (V), actinomycin-D (A), and cyclophosphamide (C) in 10 patients, VAC + adriamycin in 2, VA in 1, VA + ifosfamide in 1, VC + adriamycin in 1, and none in 2. One patient had salvage chemotherapy consisting of cisplatin and etoposide. Median follow-up time was 20 years (range 7.5-33). Results: Late effects of treatment were seen in all patients and included facial growth retardation in 11, neuroendocrine dysfunction in 9, visual/orbital problems in 9, dental abnormalities in 7, hearing loss in 6, and hypothyroidism in 3. Intellectual and academic delays were documented in 3 patients who had received whole brain radiotherapy. While neuroendocrine, thyroid, dental, and cognitive sequelae were primarily attributed to radiotherapy

  16. High dose rate brachytherapy for the treatment of soft tissue sarcoma of the extremity

    International Nuclear Information System (INIS)

    Purpose: we examined the role of preoperative neoadjuvant chemoradiation and adjuvant high-dose rate brachytherapy on the management of prognostically unfavorable soft tissue sarcomas of the extremities. Our goal was to examine the effect of high dose rate interstitial brachytherapy (HDR IBT) on reducing the risk of local recurrence following limb-sparing resection, as well as shortening treatment duration. Materials and methods: eleven patients, ranging in age from 31 to 73 years old, with soft tissue sarcoma of the extremity were treated at USC/Norris Comprehensive Cancer Center during 1994 and 1995. All patients had biopsy proven soft tissue sarcoma, and all were suitable candidates for limb-sparing surgery. All lesions were greater than 5cm in size and were primarily high grade. Tumor histologies included malignant fibrous histiocytoma (45%), liposarcoma (18%) and leiomyosarcoma, synovial cell sarcoma and spindle cell sarcoma (36%). Sites of tumor origin were the lower extremity (55%), upper extremity (18%) and buttock (9%), 1 patient (9%) had lesions in both the upper and lower extremity. Patients received HDR IBT following combined chemotherapy and external beam irradiation (EBRT) and en bloc resection of the sarcoma. Neoadjuvant chemotherapy consisted of three to four cycles of either Ifosfamide/Mesna with or without Adriamycin, or Mesna, Adriamycin, Ifosfamide and Dacarbazine. One patient received Cis-platin in addition to Ifos/Adr. A minimum of two cycles of chemotherapy were administered prior to EBRT. Additional cycles of chemotherapy were completed concurrently with EBRT but prior to HDR IBT. Preoperative EBRT doses ranging from 40 to 59.4 Gy were given in daily fractions of 180 to 200cGy. Following en bloc resection, HDR IBT was administered using the Omnitrontm 2000 remote afterloading system. Doses ranging from 13 to 30 Gy were delivered to the surgical tumor bed at depths of 0.5mm to 0.75mm from the radioactive source. Results: median follow-up was

  17. Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin

    Directory of Open Access Journals (Sweden)

    Jiang SP

    2013-08-01

    . Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced. Conclusion: The present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin. Keywords: PEGylation, stability, antitumor activity

  18. Identification and Antiproliferative Activity Evaluation of a Series of Triterpenoids Isolated from Flueggea virosa (Roxb. ex Willd.

    Directory of Open Access Journals (Sweden)

    Sod Monkodkaew

    2009-01-01

    Full Text Available Problem statement: Medicinal plants derived anticancer were now being subjects of many research groups especially, the secondary metabolite triterpenoids trees which had enormous potential to inspire and influence modern antiproliferative research. The study aimed to investigate the chemical constitution and their potential use as antiproliferative activity of purified compounds derived from F. virosa. Approach: The F. virosa was selected and percolated with hexane, ethyl acetate, acetone and methanol. The extracts were purified and elucidated chemical structures. Furthermore, the isolated compounds were tested for biological activity. The bioassays were performed on two cancer cell lines, adriamycin-sensitive erythroleukemia cells (K562 and adriamycin-resistant erythroleukemia cells (K562/Adr which overexpressed P-glycoprotein (MDR1/ABCB1. Results: Friedelin (1, epifriedelanol (3, stigmasterol (4 and betulinic acid (5 were isolated from the leaves and twigs of F. virosa. The molecular structures of these compounds were determined using several spectroscopic methods. The compounds i.e., 1, a chemically modified compound 1 heptanolide (2, 3 and 4 showed a limited cytotoxic activity towards human cancer cell lines mainly due to a low aqueous solubility which prevented their use in cell viability assays. Interestingly, compound 5 exhibited a high cytotoxicity characterized by an effective concentration value (IC50 equal to 9.7±2.1 µg.mL-1 (21.2±4.6 µM and 7.1±0.7 µg.mL-1 (15.5±1.5 µM for K562 and K562/Adr, respectively. Moreover, the antiproliferative activity of compound 5 was independent of the multidrug resistance phenotype exhibited by the K562/Adr cell line suggesting that compound 5 was not the effluxes out of the K562/Adr cells by MDR1 (ABCB1. Conclusion: The results clearly showed that the betulinic acid of the four isolated compounds from F. virosa could be considered as high potential source of cytotoxic activity.

  19. SKP2 siRNA inhibits the degradation of P27kip1 and down-regulates the expression of MRP in HL-60/A cells

    Institute of Scientific and Technical Information of China (English)

    Jie Xiao; Songmei Yin; Yiqing Li; Shuangfeng Xie; Danian Nie; Liping Ma; Xiuju Wang; Yudan Wu; Jianhong Feng

    2009-01-01

    S-phase kinase-associated protein 2 (SKP2) gene is a tumor suppressor gene, and is involved in the ubiquitin-mediated degradation of P27kip1. SKP2 and P27kip1 affect the proceeding and prognosis of leukemia through regulating the proliferation, apoptosis and differentiation of leukemia cells. In this study, we explored the mechan-ism of reversing of HL-60/A drug resistance through SKP2 down-regulation. HL-60/A cells were nucleofected by Amaxa Nucleofector System with SKP2 siRNA. The gene and protein expression levels of Skp2, P27kip1, and multi-drug resistance associated protein (MRP) were determined by reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cell cycle was analyzed by flow cytometry. The 50% inhibi-tory concentration value was calculated using cytotoxic analysis according to the death rate of these two kinds of cells under different concentrations of chemotherapeutics to compare the sensitivity of the cells. HL-60/A cells showed multi-drug resistance phenotype characteristic by cross-resistance to adriamycin, daunorubicin, and arabi-nosylcytosine, due to the expression of MRP. We found that the expression of SKP2 was higher in HL-60/A cells than in HL-60 cells, but the expression of P27kip1 was lower. The expression of SKP2 in HL-60/A cells nucleo-fected by SKP2 siRNA was down-regulated whereas the protein level of P27kip1 was up-regulated. Compared with the MRP expression level in the control group (nucleo-fected by control siRNA), the mRNA and protein expression levels of MRP in HL-60/A cells nucleofected by SKP2 siRNA were lower, and the latter cells were more sensitive to adriamycin, daunorubicin, and arabi-nosylcytosine. Down-regulating the SKP2 expression and arresting cells in the G0/G1 phase improve drug sensitivity of leukemia cells with down-regulated MRP expression.

  20. Assessment of pulmonary toxicities in breast cancer patients undergoing treatment with anthracycline and taxane based chemotherapy and radiotherapy- a prospective study

    Directory of Open Access Journals (Sweden)

    Aramita Saha

    2013-12-01

    Full Text Available Background: Anthracycline based regiments and/or taxanes and adjuvant radiotherapy; the main modalities of treatment for breast cancers are associated with deterioration of pulmonary functions and progressive pulmonary toxicities. Aim: Assessment of pulmonary toxicities and impact on pulmonary functions mainly in terms of decline of forced vital capacity (FVC and the ratio of forced expiratory volume (FEV in 1 Second and FEV1/FVC ratio with different treatment times and follow ups in carcinoma breast patients receiving anthracycline and/or taxane based chemotherapy and radiotherapy. Materials and methods: A prospective single institutional cohort study was performed with 58 breast cancer patients between January 2011 to July 2012 who received either anthracycline based (37 patients received 6 cycles FAC= 5 FU, Adriamycin, Cyclophosphamide regime and radiotherapy or anthracycline and taxane based chemotherapy (21 patients received 4cycles AC= Adriamycin, Cyclophosphamide; followed by 4 cycles of T=Taxane and radiotherapy. Assessment of pulmonary symptoms and signs, chest x-ray and pulmonary function tests were performed at baseline, midcycle, at end of chemotherapy, at end radiotherapy, at 1 and 6 months follow ups and compared. By means of a two-way analysis of variance (ANOVA model, the course of lung parameters across the time points was compared. Results and Conclusion: Analysis of mean forced vital capacities at different points of study times showed definitive declining pattern, which is at statistically significant level at the end of 6th month of follow up (p=0.032 .The FEV1/FVC ratio (in percentage also revealed a definite decreasing pattern over different treatment times and at statistically significant level at 6th month follow up with p value 0.003. Separate analysis of mean FEV1/FVC ratios over time in anthracycline based chemotherapy and radiotherapy group as well as anthracycline and taxane based chemotherapy and radiotherapy group

  1. Impact of heterozygous mutations in BRCA1 and BRCA2. Sensitivity to genotoxic drugs

    International Nuclear Information System (INIS)

    The carriers of heterozygous mutations in BRCA1 / 2 have a high risk of developing breast cancer. The loss of the normal allele with consequent loss of function is frequently observed in tumor level. Since these genes involved in the cellular response to genetic damage, loss of function can determine differences in sensitivity to genotoxic agents. In this study investigated whether heterozygous mutations in BRCA1 / 2 modify the sensitivity to genotoxic drugs using lymphoblastic cell lines developed from individuals who carry no mutation carriers and heterozygous for BRCA1 / 2. Materials and methods. Chemo sensitivity of the cell lines was compared lymphoblastoid GM13709 (mutation in exon 11 of BRCA1 2187delA), GM14622 (level 607stop mutation in exon 11 of BRCA2) and GM 14453 (normal BRCA1 / 2) from exposure to Adriamycin (0.2-2.5 mM) and Cisplatin (0.625- 80mM) through the test of cell viability based on MTT reduction. It determined the inhibitory concentration 50 (IC50) from curves regression dose-response obtained after 24 hours of drug exposure. It 5 independent experiments performed in triplicate. Results. The line GM14622 was significantly (P = 0.003) more sensitive to Adriamycin (IC50: 0.585 mM) than the Control GM14453 (IC50: 1.364 mM) online while GM13709 was similar to the control (IC50: 1.324 mM) response. Turn the line GM14622 was also significantly (P = 0.01) more sensitive cisplatin (IC50: 12.7 mM) than the line GM14453 (IC50: 28.6mm) and GM13709 had the same response as the (IC50: 28.6 mM) control. Discussion and Conclusions. Our results suggest that mutations deleterious heterozygous BRCA2 may confer increased sensitivity to drugs genotoxic, which may have implications in the management of patients carrying or BRCA2 mutations in women with sporadic breast cancer exhibit low expression of BRCA2

  2. Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway.

    Science.gov (United States)

    Chen, Jie-Ru; Jia, Xiu-Hong; Wang, Hong; Yi, Ying-Jie; Wang, Jian-Yong; Li, You-Jie

    2016-05-01

    One of the major causes of failure in chemotherapy for patients with human chronic myelogenous leukemia (CML) is the acquisition of multidrug resistance (MDR). MDR is often associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) protein family. Timosaponin A-III (TAIII), a saponin isolated from the rhizome of Anemarrhena asphodeloides, has previously demonstrated the ability to suppress certain human tumor processes and the potential to be developed as an anticancer agent. Nevertheless, the ability of TAIII to reverse MDR has not yet been explored. In this study, the adriamycin (ADM) resistance reversal effect of TAIII in human CML K562/ADM cells and the underlying mechanism was investigated. The Cell Counting Kit-8 (CCK-8) assay showed that TAIII had a reversal effect on the drug resistance of K562/ADM cells. Flow cytometry assay showed increased intracellular accumulation of ADM after cells were pretreated with TAIII, and the changes in the accumulation of rhodamine-123 (Rho-123) and 5(6)-carboxyfluorescein diacetate (CFDA) dye in K562/ADM cells were determined to be similar to the changes of intracellular accumulation of ADM. After pretreatment of cells with TAIII, the decreasing expression of P-gp and MRP1 mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). Western blotting showed TAIII inhibiting P-gp and MRP1 expression depended on the PI3K/Akt signaling pathway by decreasing the activity of p-Akt. Moreover, wortmannin an inhibitor of PI3K/Akt signaling pathway has a strong inhibitory effect on the expression of p-Akt, P-gp and MRP1. Besides, the combined treatment with TAIII did not have an affect on wortmannin downregulation of p-Akt, P-gp and MRP1. Taken together, our findings demonstrate, for the first time, that TAIII induced MDR reversal through inhibition of P-gp and MRP1 expression and function with regained adriamycin sensitivity which might mainly correlate to the regulation of PI3K

  3. The inhibitory and combinative mechanism of HZ08 with P-glycoprotein expressed on the membrane of Caco-2 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanyan; Hu, Yahui; Feng, Yidong; Kodithuwakku, Nandani Darshika; Fang, Weirong [State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009 (China); Li, Yunman, E-mail: yunmanlicpu@hotmail.com [State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009 (China); Huang, Wenlong [Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009 (China)

    2014-01-15

    Recently, the research and development of agents to reverse the phenomenon of multidrug resistance has been an attractive goal as well as a key approach to elevating the clinical survival of cancer patients. Although three generations of P-glycoprotein modulators have been identified, poor clearance and metabolism render these agents too toxic to be used in clinical application. HZ08, which has been under investigation for several years, shows a dramatic reversal effect with low cytotoxicity. For the first time, we aimed to describe the interaction between HZ08 and P-glycoprotein in Caco-2 cell line in which P-glycoprotein is overexpressed naturally. Cytotoxicity and multidrug resistance reversal assays, together with flow cytometry, fluorescence microscopy and siRNA interference as well as Caco-2 monolayer transport model were employed in this study to evaluate the interaction between HZ08 and P-glycoprotein. This study revealed that HZ08 was capable of reversing adriamycin resistance mediated by P-glycoprotein as a result of intracellular enhancement of adriamycin accumulation, which was found to be superior to verapamil. In addition, we confirmed that HZ08 suppressed the transport of Rhodamine123 in the Caco-2 monolayer model but had little effect on P-glycoprotein expression. The transport of HZ08 was diminished by P-glycoprotein inhibitors (verapamil and LY335979) and its accumulation was increased via siRNA targeting MDR1 in Caco-2 cells. Furthermore, considering the binding site of P-glycoprotein, verapamil performed as a competitive inhibitor with HZ08. In conclusion, as a P-glycoprotein substrate, HZ08 inhibited P-glycoprotein activity and may share the same binding site of verapamil to P-glycoprotein. - Highlights: • The cytotoxicity and reversing effect of HZ08 was measured in Caco-2 cell line. • HZ08 inhibited the transport of Rhodamine123 across Caco-2 cell monolayer. • The efflux ratio of HZ08 was dropped when combined with P

  4. Quantitative evaluation of thallium-201 uptake in predicting chemotherapeutic response of osteosarcoma

    International Nuclear Information System (INIS)

    This study attempts to quantitate changes in tumour to normal tissue ratio following chemotherapy. Eight consecutive patients with classical osteosarcoma received standard preoperative chemotherapy with a combination of cisplatin, adriamycin and high-dose methotrexate. 201Tl gamma scintigraphic images were obtained both before and after chemotherapy. The average counts taken over the tumour divided by that from the contralateral normal tissue area yielded a tumour-to-normal tissue (T/N) ratio. The percentage change in the T/N ratio before and after preoperative chemotherapy was correlated with the percentage of tumour necrosis from pathological section. The median post-chemotherapy T/N ratio was 1.85 (range 0.5-7.7). The median percentage change in T/N ratio after chemotherapy was -58% (range +26% to -83%). The median percentage of necrosis from pathological section was 80% (range 0%-95%). There was a good correlation between the percentage of tumour necrosis and the percentage change in T/N ratio (rank correlation coefficient r=0.84, P=0.0085). Quantitative assessment of changes in 201Tl uptake by osteosarcoma correlates well with tumour necrosis after preoperative chemotherapy. This method may be used to predict response to chemotherapy at an earlier stage, enabling the clinician to consider alternative chemotherapeutic regimens or salvage surgery. (orig.)

  5. Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature

    International Nuclear Information System (INIS)

    Twenty children with soft tissue sarcomas of the head and neck, treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1972 to 1981, were evaluated for the late deleterious effects of treatment. All patients received radiation therapy and combination chemotherapy with vincristine, dactinomycin, and cyclophosphamide; certain patients also received Adriamycin (doxorubicin). All had ophthalmologic, otologic, growth, and cosmetic evaluations; 15 also had dental and maxillofacial examinations. The median age at diagnosis was 6 years (range, 7 months-13 years). Median follow-up from time of diagnosis was 5.5 years with a minimum of 3 years in all but four patients. The major problems encountered were related to the eyes (xerophthalmia and cataracts), ears (hearing loss), teeth (maleruption and caries), glandular structures (xerostomia, hypopituitarism), and development (craniofacial deformity). It is concluded that children treated for soft tissue sarcomas of the head and neck with combined modality therapy, including radiation enhancers, may show a variety of late treatment-related adversities. These children require close multidisciplinary follow-up for detection of late effects in order that appropriate prophylactic or symptomatic treatment can be instituted to minimize their consequences

  6. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Münster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen.

    Science.gov (United States)

    Rytting, Michael E; Jabbour, Elias J; Jorgensen, Jeffrey L; Ravandi, Farhad; Franklin, Anna R; Kadia, Tapan M; Pemmaraju, Naveen; Daver, Naval G; Ferrajoli, Alessandra; Garcia-Manero, Guillermo; Konopleva, Marina Y; Borthakur, Gautam; Garris, Rebecca; Wang, Sa; Pierce, Sherry; Schroeder, Kurt; Kornblau, Steven M; Thomas, Deborah A; Cortes, Jorge E; O'Brien, Susan M; Kantarjian, Hagop M

    2016-08-01

    Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen, and its comparison with hyper-fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper-CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome- (Ph) negative ALL received ABFM from October 2006 through March 2014. Their outcome was compared to 102 AYA patients (median age 27 years), treated with hyper-CVAD at our institution. The complete remission (CR) rate was 93% with ABFM and 98% with hyper-CVAD. The 5-year complete remission duration (CRD) were 53 and 55%, respectively (P = 0.98). The 5-year overall survival (OS) rates were 60 and 60%, respectively. The MRD status on Day 29 and Day 84 of therapy was predictive of long-term outcomes on both ABFM and hyper-CVAD. Severe regimen toxicities with ABFM included hepatotoxicity in 41%, pancreatitis in 11%, osteonecrosis in 9%, and thrombosis in 19%. Myelosuppression-associated complications were most significant with hyper-CVAD. In summary, ABFM and hyper-CVAD resulted in similar efficacy outcomes, but were associated with different toxicity profiles, asparaginase-related with ABFM and myelosuppression-related with hyper-CVAD. Am. J. Hematol. 91:819-823, 2016. © 2016 Wiley Periodicals, Inc. PMID:27178680

  7. A case of acute myelogenous leukemia following aplastic anemia after radiotherapy and chemotherapy for breast cancer

    International Nuclear Information System (INIS)

    A 53 years old mastectomized woman for breast cancer treated with radiotherapy (total doses 12,600 rad) and with long term oral administration of cyclophosphamide (CPM) and ftorafur (FT), developed aplastic anemia and thereafter acute myelogenous leukemia. About six months after discontinuation of the above therapies, she developed anemia and leukopenia and was referred to our clinic. Hematological improvement was obtained by the administration of anabolic hormone, however, two months later she became pancytopenic again. At that time, quite atypical myeloblasts contained peroxidase positive granules, were found 39% in the peripheral blood and 89.4% in the bone marrow, respectively. Leukemic hiatus was present. A bone marrow biopsy revealed coexistence of leukemic cells and breast cancer cells. A diagnosis of breast cancer complicated with acute myelogenous leukemia was made. A combined therapy of adriamycin, CPM and FT was ineffective. OAP regimen of vincristine, cytosine arabinoside and predonisolone revealed transient hematologic improvement. Finally, the patient died of septicemia due to klebsiella. Autopsy revealed wide spread coexistence of leukemia and cancer in the bone marrow, liver, and thyroid. The authors discuss some possible explanations for development of acute leukemia after radiotherapy and chemotherapy. (author)

  8. Enediyne lidamycin induces apoptosis in human multiple myeloma cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase.

    Science.gov (United States)

    Zhen, Yong-Zhan; Lin, Ya-Jun; Shang, Bo-Yang; Zhen, Yong-Su

    2009-07-01

    In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, on two human multiple myeloma (MM) cell lines, U266 and SKO-007, were evaluated. In MTS assay, LDM showed much more potent cytotoxicity than conventional anti-MM agents to both cell lines. The IC(50) values of LDM for the U266 and SKO-007 cells were 0.0575 +/- 0.0015 and 0.1585 +/- 0.0166 nM, respectively, much lower than those of adriamycin, dexamethasone, and vincristine. Mechanistically, LDM triggered MM cells apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in LDM-induced cell death. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed the LDM-induced apoptosis through decreasing the level of cleaved PARP and caspase-3/7. Interestingly, phosphorylation of extracellular signal-related kinase was increased by LDM; conversely, MEK inhibitor synergistically enhanced LDM-induced cytotoxicity and apoptosis in MM cells. The results demonstrated that LDM suppresses MM cell growth through the activation of p38 MAPK and JNK, with the potential to be developed as a chemotherapeutic agent for MM. PMID:19468799

  9. Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults

    International Nuclear Information System (INIS)

    Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcome (n=32), peripheral neuroepithelioma (n=14), rhabdomyosarcoma (n=24), undifferentiated sarcoma (n=5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.(author). 44 refs.; 8 figs.; 6 tabs

  10. The role of consolidation irradiation in combined modality therapy of small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Forty-four patients with small cell carcinoma of the lung (SCCL) were treated with a program of combined chemotherapy and radiation therapy. Prophylactic cranial irradiation was given concurrent with the first of six planned cycles of chemotherapy consisting of Cyclophosphamide, Adriamycin, Vincristine and high dose Methotrexate (CAV-M). All patients judged as complete responders (CR) received consolidative thoracic irradiation (CTI) to the locoregional primary lung involvement. The CR rate to chemotherapy alone was 84% for patients with limited disease (LD) and 44% for extensive disease. In comparison to a prior trial, which used similar chemotherapy, but with irradiation withheld until primary site relapse, the actuarial primary site relapse rate at 2 years was reduced by CTI from 92% to 18% (P < .01). The median primary site remission duration has not yet been reached in the CTI group and was 34 weeks without CTI (P < .01). CTI increased the 2 year actuarial survival from 6% to 66% (P < .01) in the chemotherapy CR patients.Median survival has not yet been reached in the CTI group, but was 48 weeks without CTI (P < .01). Leptomeningeal spinal cord relapse in patients with no prior central nervous system (CNS) involvement occurred in 16% of patients relapsing

  11. Pharmacological modulation of human subconjunctival fibroblast behavior in vitro.

    Science.gov (United States)

    Damji, K F; Rootman, J; Palcic, B; Thurston, G

    1990-01-01

    The response of human subconjunctival fibroblasts to a variety of pharmacological agents was evaluated utilizing a novel in vitro wound assay and a separate proliferation assay. Both colchicine and cytochalasin B dramatically arrested wound closure at concentrations greater than or equal to 0.01 micrograms/ml and 2 micrograms/ml, respectively (p less than 0.05). At lower doses these drugs altered fibroblast morphology and inhibited directed cell migration. Dexamethasone and 6-MP delayed wound closure at concentrations greater than or equal to 100 micrograms/ml and 1000 micrograms/ml, respectively (p less than 0.05). Effective antiproliferative agents, in order of decreasing potency (based on unit weight), were Cytarabine (cytosine arabinoside), doxorubicin (Adriamycin), colchicine, 5-fluorouracil, cytochalasin B, cyclosporin (Sandimmune), 6-mercaptopurine, and dexamethasone. The antiprotease agents and methotrexate were ineffective as determined by both assays. We conclude that the wound assay is well suited for rapid screening of drugs for their effect on fibroblast morphology, motility, and proliferation, and that colchicine and cytochalasin B, in doses well below those documented to produce ocular toxicity, are effective in inhibiting directed migration and proliferation of subconjunctival fibroblasts in vitro. Differences in mechanism, onset of action, therapeutic range, and cytotoxicity of drugs could be exploited in controlling ocular fibroblast behavior in vivo. PMID:2325993

  12. Radiation response of drug-resistant variants of a human breast cancer cell line: The effect of glutathione depletion

    International Nuclear Information System (INIS)

    Two drug-resistant variants of the human breast cancer cell line MCF-7 have been shown previously to exhibit radiation resistance associated with an increase in the size of the shoulder on the radiation survival curve. In the present study, glutathione (GSH) depletion was achieved by exposure of cells to buthionine sulfoximine (BSO) with, in some cases, additional treatment with dimethyl fumarate. Levels of GSH in the adriamycin-resistant subline MCF-7 ADRR are initially lower than in the other two sublines and are depleted to a greater extent by exposure to BSO. Wild-type MCF-7 cells are not sensitized by GSH depletion when irradiated under aerated conditions but are sensitized under hypoxic conditions to an extent which is related to the level of GSH depletion. In contrast both the drug-resistant sublines (MCF-7 ADRR and the melphalan-resistant line MCF-7 MLNR) are radiosensitized by GSH depletion under both aerated and hypoxic conditions. It is hypothesized that in the case of the MCF-7 ADRR cell line, which expresses high levels of the GSH-associated redox enzyme systems, GSH-S-transferase and GSH-peroxidase (GSH-Px), radiosensitization results when GSH-Px is inhibited in GSH-depleted cells. The reasons for radiosensitization of aerated MCF-7 MLNR cells cannot be explained on this basis, however, and other factors are being examined

  13. Modification of radio- and thermo-sensitivity by amrubicin or amrubicinol in human lung adenocarcinoma A549 cells

    International Nuclear Information System (INIS)

    Amrubicin (AMR) is a totally synthetic 9-aminoanthracyclin anticancer drug. It is considered that AMR is an inhibitor of DNA topoisomerase II as the case of another anthracyclin anticancer drug, adriamycin (ADM) (1), which has significant antitumor activity against a broad spectra of human malignancies. The antitumor activity of AMR was found superior to that of ADM in experimental therapeutic models of human tumor xenografts (nude mouse). AMR was converted in vivo to major metabolite, amrubicinol (AMROH), which was markedly more effective cytotoxic agent than the mother compound. In the clinical studies currently conducted on malignant lymphoma, non-small or small cell lung carcinoma, the activity of AMR was shown very promising. However, the interactive cytocidal effects of the combined treatment with AMR or AMROH and radiation or hyperthermia are under investigation. In the present study, we examined chemical modification of radio- and thermo-sensitivity by AMR or AMROH in cultured human lung adenocarcinoma A549 cells. Sublethal damage repair (SLDR) was inhibited by the pretreatment with AMR or AMROH followed by X-irradiation. This finding suggests the possibility of the combined treatment of AMR or AMROH and X-irradiation as clinical cancer therapy strategy, since the doses in the routine clinical radiotherapy is ranged with a sublethal dose of 2 Gy. We also found that SLDR was inhibited by the pretreatment with AMR or AMROH followed by hyperthermia. We will discuss about clinical adoption of the combined treatment with AMR or AMROH and radiation or hyperthermia

  14. Differential impact of diverse anticancer chemotherapeutics on the Cdc25A-degradation checkpoint pathway

    International Nuclear Information System (INIS)

    When exposed to DNA-damaging insults such as ionizing radiation (IR) or ultraviolet light (UV), mammalian cells activate checkpoint pathways to halt cell cycle progression or induce cell death. Here we examined the ability of five commonly used anticancer drugs with different mechanisms of action to activate the Chk1/Chk2-Cdc25A-CDK2/cyclin E cell cycle checkpoint pathway, previously shown to be induced by IR or UV. Whereas exposure of human cells to topoisomerase inhibitors camptothecin, etoposide, or adriamycin resulted in rapid (within 1 h) activation of the pathway including degradation of the Cdc25A phosphatase and inhibition of cyclin E/CDK2 kinase activity, taxol failed to activate this checkpoint even after a prolonged treatment. Unexpectedly, although the alkylating agent cisplatin also induced degradation of Cdc25A (albeit delayed, after 8-12 h), cyclin E/CDK2 activity was elevated and DNA synthesis continued, a phenomena that correlated with increased E2F1 protein levels and consequently enhanced expression of cyclin E. These results reveal a differential impact of various classes of anticancer chemotherapeutics on the Cdc25A-degradation pathway, and indicate that the kinetics of checkpoint induction, and the relative balance of key components within the DNA damage response network may dictate whether the treated cells arrest their cell cycle progression

  15. Preformulation Studies on Piperlongumine.

    Directory of Open Access Journals (Sweden)

    Alhassan Aodah

    Full Text Available Piperlongumine is a natural alkaloid extracted from piper plants which has been used traditionally for the treatment of certain diseases. This compound shows interesting in vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties for this compound have not been well characterized. In this research, preformulation studies for piperlongumine have been performed to determine factors which influence solubility and stability which, in turn, can be used to assist future formulation development. The solubility of piperlongumine in water was found to be approximately 26 μg/ml. Using 10% polysorbate 80 as a surfactant resulted in a 27 fold increase in solubility. Cosolvents and cyclodextrins afforded concentrations of 1 mg/ml and higher. The pH degradation rate profile for piperlongumine at various temperatures shows significant instability of the drug at pH values ≥ 7 and 3, and maximum stability around pH 4. It was estimated that it would take approximately 17 weeks for piperlongumine to degrade by 10% at 25°C, pH 4. Additionally, piperlongumine showed marked photo-degradation upon exposure to an ultraviolet light source, especially in aqueous media.

  16. Preformulation Studies on Piperlongumine.

    Science.gov (United States)

    Aodah, Alhassan; Pavlik, Aaron; Karlage, Kelly; Myrdal, Paul B

    2016-01-01

    Piperlongumine is a natural alkaloid extracted from piper plants which has been used traditionally for the treatment of certain diseases. This compound shows interesting in vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties for this compound have not been well characterized. In this research, preformulation studies for piperlongumine have been performed to determine factors which influence solubility and stability which, in turn, can be used to assist future formulation development. The solubility of piperlongumine in water was found to be approximately 26 μg/ml. Using 10% polysorbate 80 as a surfactant resulted in a 27 fold increase in solubility. Cosolvents and cyclodextrins afforded concentrations of 1 mg/ml and higher. The pH degradation rate profile for piperlongumine at various temperatures shows significant instability of the drug at pH values ≥ 7 and 3, and maximum stability around pH 4. It was estimated that it would take approximately 17 weeks for piperlongumine to degrade by 10% at 25°C, pH 4. Additionally, piperlongumine showed marked photo-degradation upon exposure to an ultraviolet light source, especially in aqueous media. PMID:26982320

  17. Radiotherapy, chemotherapy, and growth-hormone deficiency

    International Nuclear Information System (INIS)

    Measurements have been made of the growth hormone (GH) responses of nine children with acute lymphoblastic leukaemia to the insulin and arginine tolerance tests. All the patients had received induction treatment with prednisone, vincristine and doxorubicin ('Adriamycin') for 4 weeks followed by 2400 rad of orthovoltage cranial irradiation plus five intrathecal injections of methotrexate. During the study all the children were in complete remission, which had been maintained with 6-mercaptopurine and methotrexate for 4 to 26 months. No pulses of steroids were used in remission. Five patients in early remission did not respond to either stimulation test, three having longer remissions showed a late and low response to the insulin test and the one patient with the longest remission (26 months) had a normal GH response. Heights and bone ages were normal. These results, which suggest the possibility of a gradual recovery after the end of CNS treatment including orthovoltage cranial irradiation, are contrasted with those for megavoltage treatment reported by Shalet et al. (Shalet, S.M., Beardwell, C.G., Morris-Jones, P.H., Pearson, D., Archs. Dis. Childh., 1976, vol. 51, 489). (U.K.)

  18. Involved Node Radiation Therapy: An Effective Alternative in Early-Stage Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Purpose: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. Methods and Materials: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. Results: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. Conclusions: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL

  19. Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc.

    Science.gov (United States)

    Puca, Rosa; Nardinocchi, Lavinia; Bossi, Gianluca; Sacchi, Ada; Rechavi, Gideon; Givol, David; D'Orazi, Gabriella

    2009-01-01

    The maintenance of p53 transactivation activity is important for p53 apoptotic function. We have shown that stable knockdown of HIPK2 induces p53 misfolding with inhibition of p53 target gene transcription. In this study we established a lentiviral-based system for doxycyclin (Dox)-induced conditional interference of HIPK2 expression to evaluate the molecular mechanisms involved in p53 deregulation. We found that HIPK2 knockdown induced metallothionein 2A (MT2A) upregulation as assessed by RT-PCR analysis, increased promoter acetylation, and increased promoter luciferase activity. The MT2A upregulation correlated with resistance to Adriamycin (ADR)-driven apoptosis and with p53 inhibition. Thus, acute knockdown of HIPK2 (HIPK2i) induced misfolded p53 protein in MCF7 breast cancer cells and inhibited p53 DNA-binding and transcription activities in response to ADR treatment. Previous works show that MT may modulate p53 activity through zinc exchange. Here, we found that inhibition of MT2A expression by siRNA in the HIPK2i cells restored p53 transcription activity. Similarly zinc supplementation to HIPK2i cells restored p53 transcription activity and drug-induced apoptosis. These data support the notion that MT2A is involved in p53 deregulation and strengthen the possibility that combination of chemotherapy and zinc might be useful to treat tumors with inactive wtp53. PMID:18996371

  20. Downregulation of wild-type p53 protein by HER-2/neu mediated PI3K pathway activation in human breast cancer cells:its effect on cell proliferation and implication for therapy

    Institute of Scientific and Technical Information of China (English)

    Li ZHENG; Jia Qiang REN; Hua LI; Zhao Lu KONG; Hong Guang ZHU

    2004-01-01

    Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30%of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy.Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer ceils. Blockage of PI3K pathway with its specific inhibitor LY294002 caused G1-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.

  1. Pregnancy and cavernous sinus syndrome in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2013-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL usually present with rapidly growing lymph nodes or extra-nodal masses. Central nerve system involvement and pregnancy are rare in DLBCL. Here, we report an unusual case of DLBCL with cavernous sinus syndrome during pregnancy. A 24-year-old woman presented cavernous sinus syndrome as the initial presentation during pregnancy. Magnetic resonance imaging (MRI revealed enlargement of bilateral cavernous sinus. Tonsil and ovary biopsy indicated malignant lymphoma-DLBCL. Bone marrow smear showed infiltration by tumor cells. The case delivered a viable baby by cesarean section and then took chemotherapy of rituxan, cyclophosphamide, adriamycin, eldisine and dexamethasone. The disease deteriorated rapidly, especially after the pregnancy was terminated. Fortunately, a complete response was achieved after six cycles of chemotherapy. With the accumulation of clinical practice of such cases, we would be able to recognize minimal symptoms of DLBCL at the beginning and confirm the most suitable timing of the initiation of chemotherapy during pregnancy.

  2. Involved Node Radiation Therapy: An Effective Alternative in Early-Stage Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Maraldo, Maja V., E-mail: dra.maraldo@gmail.com [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Aznar, Marianne C. [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Faculty of Health Sciences, University of Copenhagen, Copenhagen (Denmark); Vogelius, Ivan R.; Petersen, Peter M. [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Specht, Lena [Department of Radiation Oncology, The Finsen Center, Rigshospitalet, Copenhagen (Denmark); Faculty of Health Sciences, University of Copenhagen, Copenhagen (Denmark)

    2013-03-15

    Purpose: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. Methods and Materials: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. Results: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. Conclusions: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.

  3. Culture of human cell lines by a pathogen-inactivated human platelet lysate.

    Science.gov (United States)

    Fazzina, R; Iudicone, P; Mariotti, A; Fioravanti, D; Procoli, A; Cicchetti, E; Scambia, G; Bonanno, G; Pierelli, L

    2016-08-01

    Alternatives to the use of fetal bovine serum (FBS) have been investigated to ensure xeno-free growth condition. In this study we evaluated the efficacy of human platelet lysate (PL) as a substitute of FBS for the in vitro culture of some human cell lines. PL was obtained by pools of pathogen inactivated human donor platelet (PLT) concentrates. Human leukemia cell lines (KG-1, K562, JURKAT, HL-60) and epithelial tumor cell lines (HeLa and MCF-7) were cultured with either FBS or PL. Changes in cell proliferation, viability, morphology, surface markers and cell cycle were evaluated for each cell line. Functional characteristics were analysed by drug sensitivity test and cytotoxicity assay. Our results demonstrated that PL can support growth and expansion of all cell lines, although the cells cultured in presence of PL experienced a less massive proliferation compared to those grown with FBS. We found a comparable percentage of viable specific marker-expressing cells in both conditions, confirming lineage fidelity in all cultures. Functionality assays showed that cells in both FBS- and PL-supported cultures maintained their normal responsiveness to adriamycin and NK cell-mediated lysis. Our findings indicate that PL is a feasible serum substitute for supporting growth and propagation of haematopoietic and epithelial cell lines with many advantages from a perspective of process standardization, ethicality and product safety. PMID:25944665

  4. Primary lymphoma of the liver treated by extended hepatectomy and chemotherapy: a case report Linfoma primário do fígado tratado por hepatectomia ampliada e quimioterapia: relato de caso

    Directory of Open Access Journals (Sweden)

    Eleazar Chaib

    2002-09-01

    Full Text Available Primary lymphoma of the liver is an extremely rare entity. A case of anaplastic large B-cell (both CD-20 and lambda positive non-Hodgkin's lymphoma that was confined to the liver in a 33-year-old man is reported. The patient was treated with an extended right hepatectomy and combination chemotherapy: cyclophosphamide, adriamycin, vincristine, and prednisone. The patient was disease free 24 months after the procedure.O linfoma primário do fígado é uma entidade extremamente rara. Os autores relatam um caso de linfoma não-Hodgkin de células B grandes anaplásicas (positivo para CD-20 e Lambda em um paciente do sexo masculino de 33 anos. O tumor estava localizado no lobo hepático direito e foi tratado por hepatectomia direita ampliada e quimioterapia pós-operatória com ciclofosfamida, adriamicina, vincristina e prednisone. Vinte quatro meses de seguimento o paciente encontra-se sem recidiva tumoral.

  5. Bleomycin, adiamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin`s lymphoma. Long-term survival rate and complications

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Kouichi; Yasuda, Shigeo; Itami, Jun [Chiba Univ. (Japan). School of Medicine] [and others

    1998-06-01

    This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin`s lymphoma. Seventy patients with non-Hodgkin`s lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival. (author)

  6. Sequential chemoradiotherapy for stage I/II nasal natural killer/T cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Young Joo [Ulsan University Hospital, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Ahn, Yong Chan; Kim, Won Seog; Ko, Young Hyeh [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Authors would report the results of sequential CHOP chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisone) and involved field radiotherapy (IFRT) for early stage nasal natural killer/T-cell lymphoma (NKTCL). Fourteen among 17 patients, who were registered at the Samsung Medical Center tumor registry with stage I and II nasal NKTCL from March 1995 to December 1999 received this treatment protocol. Three to four cycles of CHOP chemotherapy were given at 3 weeks' interval, which was followed by local IFRT including the known tumor extent and the adjacent draining lymphatics. Favorable responses after chemotherapy (before IFRT) were achievable only in seven patients (5 CR's + 2 PR's: 50%), while seven patients showed disease progression. There were six patients with local failures, two with distant relapses, and none with regional lymphatic failure. The actuarial overall survival and progression-free survival at 3 years were 50.0% and 42.9%. All the failures and deaths occurred within 13 months of the treatment start. The factors that correlated with the improved survival were the absence of 'B' symptoms, the favorable response to chemotherapy and overall treatment, and the low risk by international prognostic index on univariate analyses. Compared with the historic treatment results by IFRT either alone or followed by chemotherapy, the current trial failed to demonstrate advantages with respect to the failure pattern and survival. Development of new treatment strategy in combining IFRT and chemotherapy is required for improving outcomes.

  7. Rituximab plus Ifosfamide, Carboplatin and Etoposide for T-Cell/Histiocyte-Rich B-Cell Lymphoma Arising in Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma

    Directory of Open Access Journals (Sweden)

    Hyung-Chul Park

    2012-08-01

    Full Text Available A small subset of patients with nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHLs develop a non-Hodgkin lymphoma either concurrently or subsequently, usuallyT-cell/histiocyte-rich B-cell lymphomas (T/HRBCL, which are subtypes of diffuse large B-cell lymphomas (DLBCL. The standard treatment of DLBCL patients is rituximab-based chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone. However, the administration of this chemotherapy regimen to patients with DLBCL arising in NLPHL brings concern about the cardiac toxicity of anthracycline because the majority of these patients had already received anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine at the time of NLPHL. Herein, we report 2 patients with sequential transformation of NLPHL to T/HRBCL. They initially presented with limited-stage NLPHL and subsequently developed T/HRBCL after 16 and 8 months, respectively. At the time of T/HRBCL, they were treated with rituximab, ifosfamide, carboplatin and etoposide, and complete responses were obtained.

  8. The Management of Classical Hodgkin's Lymphoma: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    S. E. Richardson

    2011-01-01

    Full Text Available The management of classical Hodgkin's lymphoma (CHL is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT. Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.

  9. Wilms tumor in adult: case report; Tumor de Wilms em adulto: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Albuquerque, Mauro Guimaraes; Vieira, Sabas Carlos; Rego, Cristiane Fortes Napoleao do [Universidade Estadual do Piaui (UESPI), Teresina, PI (Brazil); Fortes, Emanuel Augusto de C.; Santana, Gerusia Ibiapina [Hospital Sao Marcos, Teresina, PI (Brazil)]. E-mail: sabasvieira@uol.com.br

    2004-07-01

    Wilms' tumor is the renal tumor with the higher incidence on the childhood, however it rarely occurs in adults.The incidence in this group is estimated at about 1% of all the cases and they have an obscure prognosis. In this report is related a new case in a 52 years old man presenting intensive abdominal pain associated by weightiness. Abdominal ultrasound revealed expansive and complex lesion with indefinite contour in the left flank. Computed tomography of abdomen demonstrated solid lesion on antero-superior pole of the left kidney invading para-vertebral musculature, peri and para-renal spaces. Total nephrectomy and the histopathologic analysis were realized. A nephroblastoma (Wilms' tumor) in stage II without anaplasia was diagnosed by the anatomopathological studies.Local radiotherapy was applied. Thereafter was diagnosed pulmonary and hepatic metastasis, and then initiated the chemotherapy with adriamycin, actinomycin and vincristine. The prognosis of Wilms' tumor is worse in adult and it requires an aggressive therapeutic and follow up. (author)

  10. Primary central nervous system lymphoma. The clinical features and treatment of 22 cases

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Takao; Suzumiya, Junji; Tomonaga, Masamichi; Kikuchi, Masahiro; Tamura, Kazuo [Fukuoka Univ. (Japan). School of Medicine; Shibuya, Tunefumi [Hamanomachi Hospital, Fukuoka (Japan); Tukada, Junichi [Univ. of Occupational and Environmental Health, Kitakyushu (Japan)

    2002-04-01

    The purpose of this study was to clarify the efficacy of chemotherapy after radiation therapy in immunocompetent patients with primary central nervous system lymphoma (PCNSL). A retrospective analysis of 22 PCNSL patients was performed. Twenty-two patients were divided into a combined treatment (chemotherapy after radiation) group and a radiation group. The survival curves, calculated according to the Kaplan and Meier method, were compared using the Log-rank and Wilcoxon statistical analyses. Eight patients were treated with radiation therapy alone, and their median survival time (MST) after diagnosis was 21.9 months. Fourteen patients were treated with chemotherapy after radiotherapy. Six patients received chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP), while 6 patients received carboplatin-based chemotherapy and 2 patients received methotrexate-based chemotherapy. The MST of these 14 patients was 34.4 months, which was not significantly better than that of the radiation therapy group (p=0.159). Leukoencephalopathy occurred in 3 patients, who received whole brain radiation. The use of chemotherapy after radiation has up to now been thought to be a standard treatment modality but CHOP or carboplatin-based chemotherapy did not improve the survival time. (author)

  11. Primitive neuroectodermal tumor of adrenal: Clinical presentation and outcomes

    Directory of Open Access Journals (Sweden)

    Deep Dutta

    2013-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET of adrenal is an extremely rare tumor of neural crest origin. A nonfunctional left adrenal mass (14.6 × 10.5 × 10.0 cm on computed tomography (CT was detected in a 40-year-old lady with abdominal pain, swelling, and left pleural effusion. She underwent left adrenalectomy and left nephrectomy with retroperitoneal resection. Histopathology revealed sheets and nest of oval tumor cells with hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm, brisk mitotic activity, necrosis, lymphovascular invasion, capsular invasion, and extension to the surrounding muscles; staining positive for Mic-2 (CD-99 antigen, vimentin, synaptophysin, and Melan-A. Thoracocentesis, pleural fluid study, and pleural biopsy did not show metastasis. She responded well to vincristine, adriamycin, and cyclophosphamide followed by ifosfamide and etoposide (IE. This is the first report of adrenal peripheral PNET (pPNET from India. This report intends to highlight that pPNET should be suspected in a patient presenting with huge nonfunctional adrenal mass which may be confused with adrenocortical carcinoma.

  12. Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma.

    Science.gov (United States)

    Baek, Sungmin; Lee, Young-Suk; Shim, Hye-Eun; Yoon, Sik; Baek, Sun-Yong; Kim, Bong-Seon; Oh, Sae-Ock

    2011-09-01

    A low serum level of vitamin D has been associated with an increased incidence of gastrointestinal tract cancers. However, the effects of vitamin D3 have not been investigated in gastric cancer and cholangiocarcinoma. In the present study, we found that vitamin D3 treatment significantly suppressed the viability of gastric cancer and cholangiocarcinoma cells. Moreover, vitamin D3 had a synergistic effect with other anti-cancer drugs, such as paclitaxel, adriamycin, and vinblastine, for suppressing cell viability. To determine the underlying mechanism involved in the regulation of viability by vitamin D3, we examined the effects of vitamin D3 on expression of hedgehog signaling target genes, which has been associated with gastric cancer and cholangiocarcinoma. Vitamin D3 treatment decreased the level of mRNA expression of patched1, Gli1, cyclin D1, and Bcl2, suggesting the possibility that vitamin D3 may act through regulation of hedgehog signaling. From the above results, we conclude that vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma. PMID:22025972

  13. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    International Nuclear Information System (INIS)

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase

  14. The overexpression of MRP4 is related to multidrug resistance in osteosarcoma cells

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    Zhonghui He

    2015-01-01

    Full Text Available Doxorubicin (Adriamycin, ADM is an antimitotic drug used in the treatment of a wide range of malignant tumors, including acute leukemia, lymphoma, osteosarcoma, breast cancer, and lung cancer. Multidrug resistance-associated proteins (MRPs are members of a superfamily of ATP-binding cassette (ABC transporters, which can transport various molecules across extra- and intra-cellular membranes. The aim of this study was to investigate whether there was a correlation between MRP4 and primary ADM resistance in osteosarcoma cells. In this paper, we chose the human osteosarcoma cell line MG63, ADM resistant cell line MG63/DOX, and the patient′s primary cell GSF-0686. We checked the ADM sensitivity and cytotoxicity of all the three cells by cell proliferation assay. The intracellular drug concentrations were measured by using LC-MS/MS. We also examined MRP4 gene expression by RT-PCR and Western Blot. We found that the intracellular ADM concentration of the parent osteosarcoma cell line MG63 was higher than the ADM resistant osteosarcoma MG63/DOX cell line or the GSF-0686 cell after ADM treatment (P < 0.05. In addition, MRP4 mRNA and protein levels in ADM resistant osteosarcoma cells were higher than in MG63 cell (P < 0.05. Taking together, this work suggests that overexpression of MRP4 may confer ADM resistance in osteosarcoma cells.

  15. ISPTM: an iterative search algorithm for systematic identification of post-translational modifications from complex proteome mixtures.

    Science.gov (United States)

    Huang, Xin; Huang, Lin; Peng, Hong; Guru, Ashu; Xue, Weihua; Hong, Sang Yong; Liu, Miao; Sharma, Seema; Fu, Kai; Caprez, Adam P; Swanson, David R; Zhang, Zhixin; Ding, Shi-Jian

    2013-09-01

    Identifying protein post-translational modifications (PTMs) from tandem mass spectrometry data of complex proteome mixtures is a highly challenging task. Here we present a new strategy, named iterative search for identifying PTMs (ISPTM), for tackling this challenge. The ISPTM approach consists of a basic search with no variable modification, followed by iterative searches of many PTMs using a small number of them (usually two) in each search. The performance of the ISPTM approach was evaluated on mixtures of 70 synthetic peptides with known modifications, on an 18-protein standard mixture with unknown modifications and on real, complex biological samples of mouse nuclear matrix proteins with unknown modifications. ISPTM revealed that many chemical PTMs were introduced by urea and iodoacetamide during sample preparation and many biological PTMs, including dimethylation of arginine and lysine, were significantly activated by Adriamycin treatment in nuclear matrix associated proteins. ISPTM increased the MS/MS spectral identification rate substantially, displayed significantly better sensitivity for systematic PTM identification compared with that of the conventional all-in-one search approach, and offered PTM identification results that were complementary to InsPecT and MODa, both of which are established PTM identification algorithms. In summary, ISPTM is a new and powerful tool for unbiased identification of many different PTMs with high confidence from complex proteome mixtures. PMID:23919725

  16. Limited small cell lung cancer

    International Nuclear Information System (INIS)

    This paper assesses the prognosis of patients with limited small cell lung cancer (LSCLC) not achieving complete response (CR) to induction combination chemotherapy (ICC) but who achieve CR after thoracic irradiation (TI). Twenty-four patients had CRs to ICC (CR- ICC) of two cycles of cytoxan, Adriamycin, and vincristine alternating with two cycles of cisplatin with VP-16. Another 24 had CR after consolidation with subsequent T1 (CR-T1): 45 Gy in daily fractions of 2.5 Gy or twice-daily fractions of 1.5 Gy. The CR-ICC and CR-TI patients had similar prognostic factors and treatment. Comparing CR-ICC and CR-TI, survival was 40% versus 26% at 2 years and 35% versus 4% at 5 years (P < .05). There were eight (33%) long-term survivors (≥3 years) in the CR-ICC group versus three (13%) in the CR-TI group. Local control for CR-ICC patients was 59% at 5 years versus 21% for the CR-TI patients (not significant). Freedom from DM for the CR-ICC patients was 41% at 5 years versus 8% for the CR-TI patients (P < .05)

  17. Treatment results for stage I and II non-Hodgkin's lymphomas of the head and neck

    International Nuclear Information System (INIS)

    This study analyzes the results of 129 patients with stage I and II non-Hodgkin's lymphomas of the head and neck treated at the National Cancer Center Hospital from 1969 to 1987. The 5 year survival rates of primary Waldeyer's ring lymphoma according to stage were 72.7% of stage I and 58.9% of stage II. Survival rates in patients treated with combined radiation and chemotherapy were superior to the rates of those treated with radiation alone (67.2% vs 50.4%). After adriamycin (ADM) was introduced, disease free survival rate was improved (ADM+, 59.2%; ADM-, 46.2%). The main histologic subtype and phenotypes were B-cell, and diffuse large cell type. The 5 year survival rates of sinonasal lymphomas were 15.7% of primary nasal lymphoma and 17.1% of paranasal sinuses. Several clinicopathologic differences were observed between nasal and paranasal lymphomas: 1) Local recurrence occurred more often in nasal lymphoma, 2) The main histologic subtypes and phenotypes of nasal lymphoma were T-cell, diffuse medium sized cell type contrary to B-cell, and diffuse large cell type in paranasal lymphoma. The 5 years survival rates primary lymphomas of cervical lymph nodes were better for stage II patients (77.8%) than those for stage I patients (54.5%). This may have been due to poor outcome of stage I patients treated with radiation alone. In histologic subtypes, survival rate was not significantly different for diffuse and follicular types. (author)

  18. Bleomycin, adiamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin's lymphoma. Long-term survival rate and complications

    International Nuclear Information System (INIS)

    This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin's lymphoma. Seventy patients with non-Hodgkin's lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival. (author)

  19. Pyrophosphate-bridged complexes with picomolar toxicity.

    Science.gov (United States)

    Ikotun, Oluwatayo F; Higbee, Elizabeth M; Ouellette, Wayne; Doyle, Robert P

    2009-09-01

    Recently, we have observed the emergence of a new series of pyrophosphate-bridged coordination complexes. Such complexes have been prepared by overcoming the ready hydrolysis of the pyrophosphate moiety. To date, no exploration has been conducted on the cytotoxicity of such complexes. Three pyrophosphate-bridged complexes, namely {[Ni(phen)(2)](2)(mu-P(2)O(7))}.27H(2)O, {[Cu(phen)(H(2)O)](2)(mu-P(2)O(7))}.8H(2)O and {[Co(phen)(2)](2)(mu-P(2)O(7))}.6MeOH, (where phen is 1,10'-phenanthroline) were chosen for their comparative structural similarities and suitable aqueous solubility. Cytotoxicity studies in the adriamycin-resistant ovarian cancer cell line A2780/AD demonstrated highly significant efficacy, with values as low as 160pM for the cobalt complex at 72h. The underlying mechanism for such exceptional toxicity is investigated focusing on DNA interactions, topoisomerase I enzyme inhibition and oxidative stress (followed by intracellular glutathione levels). The role of hydrolysis in uptake and toxicity is also explored (followed by electronic absorption spectroscopy, (31)P NMR, and confocal microscopy) and the complexes are compared to cisplatin controls. Overall a clear picture of the extraordinary toxicity emerged. The results demonstrate a new class of prodrugs with significant potential for future development for the treatment of drug-resistant cancer cell lines. PMID:19666193

  20. Effect of Neoadjuvant CAF Regimen on the Expression of BCSG1 in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    LIU Wei; ZHANG Xianghong; ZHANG Zhigang; WANG Xiaoling; WANG Junling; YAN Xia

    2006-01-01

    Objective: To evaluate the efficacy of neoadjuvant chemotherapy and explore a sensitive and objective way in the evaluation of neoadjuvant chemotherapy, the pathological changes and BCSG1 expression were studied by pathological and immunohistochemical method in breast cancer patients with CAF neoadjuvant chemotherapy (Cyclophosphamide, Adriamycin and Fluorouracil, CAF) and those without at the same period. Methods: Specimens were obtained from 34 breast cancer patients receiving neoadjuvant CAF regimen chemotherapy (CAF group) and 110 breast cancer patients not receiving neoadjuvant chemotherapy (control group). The BCSG1 expression was detected by SP immunohistochemistry.Correlation between BCSG1 expression and pathological response to CAF neoadjuvant chemotherapy was analyzed. Results: Overall response rate to neoadjuvant chemotherapy was 79.4%. The strong cytoplasm expression of BCSG1 was significantly lower in CAF group than in control group (29.4% vs. 64.5%,P<0.01). In CAF group, the positive cytoplasm expression in partial response (PR) (grade Ⅱ) cases was significantly lower than that in no response (NR) (grade Ⅲ) cases (P=0.002). Conclusion: Neoadjuvant chemotherapy of CAF regimen could decrease the nuclear expression of BSCG1 in breast cancer.

  1. Radiation therapy for unresected gastric lymphoma

    International Nuclear Information System (INIS)

    Six consecutive patients with unresected gastric lymphoma which were treated by radiation therapy between November 1976 and March 1989 were reviewed. Radiation therapy was performed using involved fields, total radiation dosages of which ranged from 25.2 to 36 Gy (mean, 29.3 Gy). Five out of the 6 patients were treated with chemotherapy combined with radiation. Regimen of the chemotherapy was CHOP (cyclophophamide, adriamycin, vincristine and prednisone) in most cases. Three out of the 6 underwent probe laparotomy, but the tumors were diagnosed as unresectable due to locally invading the adjacent structures. They were treated by chemo-radiotherapy and 2 of them are surviving as of the present study (40 and 116 months). The other 3 patients were diagnosed as with clinical stage IV disease and 2 of them were successfully treated with chemo-radiotherapy (21 and 66 months, surviving). These data suggest that unresected gastric lymphomas, which are locally advanced or stage IV disease, are treated by chemo-radiotherapy with high curability without any serious complications. (author)

  2. A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

    Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.

  3. Clinical applications of continuous infusion chemotherapy ahd concomitant radiation therapy

    International Nuclear Information System (INIS)

    This book presents information on the following topics: theoretical basis and clinical applications of 5-FU as a radiosensitizer; treatment of hepatic metastases from gastro intestingal primaries with split course radiation therapy; combined modality therapy with 5-FU, Mitomycin-C and radiation therapy for sqamous cell cancers; treatment of bladder carcinoma with concomitant infusion chemotherapy and irradiation; a treatment of invasiv bladder cancer by the XRT/5FU protocol; concomitant radiation therapy and doxorubicin by continuous infusion in advanced malignancies; cis platin by continuous infusion with concurrent radiation therapy in malignant tumors; combination of radiation with concomitant continuous adriamycin infusion in a patient with partially excised pleomorphic soft tissue sarcoma of the lower extremeity; treatment of recurrent carcinoma of the paranasal sinuses using concomitant infusion cis-platinum and radiation therapy; hepatic artery infusion for hepatic metastases in combination with hepatic resection and hepatic radiation; study of simultaneous radiation therapy, continuous infusion, 5FU and bolus mitomycin-C; cancer of the esophagus; continuous infusion VP-16, bolus cis-platinum and simultaneous radiation therapy as salvage therapy in small cell bronchogenic carcinoma; and concomitant radiation, mitomycin-C and 5-FU infusion in gastro intestinal cancer

  4. Similarities in cellular inactivation by hyperthermia or by ethanol

    International Nuclear Information System (INIS)

    The question of how cells are inactivated by mild hyperthermia (41 to 450C) is difficult to resolve because heat stresses most (if not all) cellular organelles. As a result, studies showing correlations between cell death resulting from heat exposure and damage to specific subcellular units tend to be inconclusive. We have looked for a heat analog, i.e., another agent whose mode of cell inactivation closely resembles that of heat. Our hypothesis is that information about the mechanism of cell inactivation closely resembles that of heat. Our hypothesis is that information about the mechanism of cell inactivation by this agent should aid in identifying the targets for heat inactivation. Here we report results that we interpret as showing that ethanol may be such an analog. Exposure of cells to heat or ethanol induces tolerance to heat, ethanol, or adriamycin. The cytotoxicity of both ethanol and heat is enhanced by low pH and cysteamine; it is reduced by deuterium oxide. Finally, treating cells either before or after x irradiation with either agent enhances cell killing

  5. Cardioprotective and neuroprotective roles of oleuropein in olive.

    Science.gov (United States)

    Omar, Syed Haris

    2010-07-01

    Traditional diets of people living in the Mediterranean basin are, among other components, very rich in extra-virgin olive oil, the most typical source of visible fat. Olive is a priceless source of monounsaturated and di-unsaturated fatty acids, polyphenolic antioxidants and vitamins. Oleuropein is the main glycoside in olives and is responsible for the bitter taste of immature and unprocessed olives. Chemically, oleuropein is the ester of elenolic acid and 3,4-dihydroxyphenyl ethanol, which possesses beneficial effects on human health, such as antioxidant, antiatherogenic, anti-cancer, anti-inflammatory and antimicrobial properties. The phenolic fraction extracted from the leaves of the olive tree, which contains significant amounts of oleuropein, prevents lipoprotein oxidation. In addition, oleuropein has shown cardioprotective effect against acute adriamycin cardiotoxicity and an anti-ischemic and hypolipidemic activities. Recently, oleuropein has shown neuroprotection by forming a non-covalent complex with the Aβ peptide, which is a key hallmark of several degenerative diseases like Alzheimer and Parkinson. Thus, a large mass of research has been accumulating in the area of olive oil, in the attempt to provide evidence for the health benefits of olive oil consumption and to scientifically support the widespread adoption of traditional Mediterranean diet as a model of healthy eating. These results provide a molecular basis for some of the benefits potentially coming from oleuropein consumption and pave the way to further studies on the possible pharmacological use of oleuropein to prevent or to slow down the cardiovascular and neurodegenerative diseases. PMID:23964170

  6. Demodex spp. Infestation in a breast-cancer patient: A case report

    Directory of Open Access Journals (Sweden)

    Serdar Olt

    2013-01-01

    Full Text Available Demodex folliculorum and Demodex brevis are obligatory parasites that live in sebaceous glands and follicles. When immune system becomes suppressed by any reason, patients become vulnerable to obligatory parasites like D. folliculorum and D. brevis. Immune system becomes suppressed in cancer patients who undergo chemotherapy, and as a result these patients become vulnerable to infestations. In our case, a 45 year-old female has been admitted to oncology clinic for a medical treatment of breast cancer. Her systematic physical examination was normal, except redness on her cheeks and forehead. There was no abnormality in biochemical and haematological laboratory values. We have decided to apply chemotherapy of Adriamycin, cyclophosphamide and 5-fluorouracil. Due to the itchy redness on her cheeks and forehead, we had performed an examination for demodex before chemotherapy; and we have identified 20 mites/cm2 on her right and left cheeks, and 15 mites/cm2 on her forehead. When our patient had came our clinic with increasing complaint of itchy rash, after the first course of chemotherapy we have reexamined demodex. The result of microscopic examination revealed large amount of demodex of 50 mites/cm2 on her right and left cheeks and 30 mites/cm2 on her forehead, which were nearly 2.5-times higher than the previous examination. This increase probably was associated with immune suppression of chemotherapy.

  7. Overexpression of ubiquitin carboxyl terminal hydrolase-L1 enhances multidrug resistance and invasion/metastasis in breast cancer by activating the MAPK/Erk signaling pathway.

    Science.gov (United States)

    Wang, Wenjuan; Zou, Liping; Zhou, Danmei; Zhou, Zhongwen; Tang, Feng; Xu, Zude; Liu, Xiuping

    2016-09-01

    Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp) exhibit enhanced invasive/metastatic ability as compared with the sensitive cells. We aimed to clarify the mechanism underlying this observation and found that during the development of drug resistance to adriamycin in MCF7 cells, the elevated expression of UCH-L1 coincides with the up-regulation of MDR1, CD147, MMP2, and MMP9 as well as increased cellular migration/invasion. Overexpression of UCH-L1 in MCF7 cells up-regulated MDR1, CD147, MMP2, and MMP9, which conferred MDR and promoted migration/invasion. On the other hand, silencing of UCH-L1 in MCF7/Adr cells led to the opposite effect. Immunohistochemistry in 203 breast cancer samples revealed that UCH-L1 expression is positively correlated with P-gp, CD147, MMP2, and MMP9 expression and standard tumor spread indicators. Kaplan-Meier survival analysis indicated a correlation between UCH-L1 expression and shorter recurrent and survival times. Moreover, UCH-L1-overexpressing clones treated with U0126 (an Erk1/2-specific inhibitor) significantly decreased the expression of MDR1, CD147, MMP2, and MMP9. These data indicate that UCH-L1 may assume a dual role, because it had intrinsic stimulatory effects on tumor migration/invasion and increased MDR. © 2015 Wiley Periodicals, Inc. PMID:26293643

  8. Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro.

    Science.gov (United States)

    Kelter, Gerhard; Schierholz, Jörg M; Fischer, Imma U; Fiebig, Heinz-Herbert

    2007-01-01

    Mistletoe extracts are widely used in complementary and alternative cancer therapy in Europe. The extracts possess cytotoxic, as well as immunostimulatory effects. However, some investigators have suggested that low doses of mistletoe extracts could also induce tumor growth. The mistletoe extracts Helixor A, Helixor M and Helixor P were investigated for growth inhibitory and stimulatory effects in a panel of 38 human tumor cell lines in vitro. Mistletoe lectin I (ML-1), adriamycin and interleukin-6 (IL-6) were used as reference compounds. All three mistletoe preparations showed cytotoxic activity [T/C (Test/Control) Control) > 125%) by the mistletoe extracts or ML-1, apart from two exceptions in the colon carcinoma cell line HCC-2998, in which Helixor M and ML-1 showed a marginal stimulation (TIC 128% and 131%, respectively) at one concentration only. Further investigations into the latter effect of Helixor M and ML-1 in the HCC-2998 line using five different proliferation assays, modified cell culture conditions and the identical production charge of mistletoe extract, as well as a new one, did not confirm the previous observation. It was concluded that the marginal stimulation found in the earlier experiments was a statistical coincidence. Helixor mistletoe preparations and ML-1 have cytotoxic activity and do not stimulate tumor cell proliferation in vitro which is in accordance with previous scientifically based observations on aqueous mistletoe extracts. PMID:17352237

  9. Investigating the pharmacodynamic and magnetic properties of pyrophosphate-bridged coordination complexes

    Science.gov (United States)

    Ikotun, Oluwatayo (Tayo) F.

    The multidentate nature of pyrophosphate makes it an attractive ligand for complexation of metal cations. The participation of pyrophosphate in a variety of biological pathways and its metal catalyzed hydrolysis has driven our investigation into its coordination chemistry. We have successfully synthesized a library of binuclear pyrophosphate bridge coordination complexes. The problem of pyrophosphate hydrolysis to phosphate in the presence of divalent metal ions was overcome by incorporating capping ligands such as 1,10-phenanthroline and 2,2'-bipyridine prior to the addition of the pyrophosphate. The magnetic properties of these complexes was investigated and magneto-structural analysis was conducted. The biological abundance of pyrophosphate and the success of metal based drugs such as cisplatin, prompted our investigation of the cytotoxic properties of M(II) pyrophosphate dimeric complexes (where M(II) is CoII, CuII, and NiII) in adriamycin resistant human ovarian cancer cells. Thess compounds were found to exhibit toxicity in the nanomolar to picomolar range. We conducted in vitro stability studies and the mechanism of cytoxicity was elucidated by performing DNA mobility and binding assays, enzyme inhibition assays, and in vitro oxidative stress studies.

  10. Effect of multidrug resistance gene-1(mdr1) overexpression on in-vitro uptake of 99mTc-sestaMIBI in murine L1210 leukemia cells

    International Nuclear Information System (INIS)

    To determine whether 99mTc-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively 99mTc-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular 99mTc-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr 1 gene) overexpression. We measured percentage uptake of 99mTc-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of 99mTc-MIBI were also evaluated with or without overexpression of mdr1 gene in cultured murine leukemia L1210 cells. The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of 99mTc-MIBI was higher in mdr1 negative L1210 cells than those of mdr1 positive cells, and higher when incubated in 37 .deg. C than 4 .deg. C. In the presence of verapamil, cyclosporin or dipyridamole, 99mTc-MIBI uptake was increased upto 604% in mdr1 positive cells. Cellular uptake of 99mTc-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest the 99mTc-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro

  11. Prognostic significance of clinico-pathological parameters in locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Organ preservation should be the main interest in the treatment of patients with locally advanced bladder cancer. The selection of patients for the respective therapy is mainly based on tumor staging, grading and multiplicity. In the present study data from 65 patients with locally advanced bladder tumors treated by an integrated chemo- radio-therapy were evaluated. The cytostatic drugs used were either Cisplatinium (19 patients (29,2 %))or Adriamycin (21 patients (32.3 %)) alone or a combination (25 patients (38,4 %)). Complete remission was achieved in 53 patients (81,5 %). The following parameters were investigated and evaluated for their prognostic significance in a multivariant analysis. 1.) Histology: tumorgrade, tumortype-papillary/solid, infiltration patterns, lymph and/or blood vessel invasion and areas of squamous cell differentiation within the tumor; 2.) Clinic: staging, tumor volume, multiplicity, therapy and hydronephrosis. The predictive value of these parameters in regard to the therapy response of the tumors was calculated. This study actually showed a statistically worse outcome for patients with papillary histology. All other parameters did not show any significance concerning the tumor remission in response to integrated radio-chemo-therapy. (author)

  12. Primary Synovial Sarcoma of Kidney: A Rare Differential Diagnosis of Renomegaly

    Directory of Open Access Journals (Sweden)

    Gaurang Modi

    2014-01-01

    Full Text Available Synovial sarcomas (SS are classified as subgroup of soft tissue sarcomas affecting mainly extremities of young adults. Primary SS of kidney are very rare tumours with poor prognosis. Though they have characteristic histology and immunohistochemistry (IHC due to rarity of incidence it is difficult to diagnose them. Sometimes chromosomal rearrangement studies are required to confirm the diagnosis. We are presenting a case of 41-year-old male who was referred to our cancer centre for evaluation of left renal mass. CT scan of abdomen revealed a large left renal mass encasing the aorta. Biopsy of renal mass revealed poorly differentiated sarcoma and IHC was positive for vimentin, CD99, and BCL2 and negative for AE1, epithelial membrane antigen, and leukocyte common antigen. The patient was clinically inoperable as renal mass was encasing the aorta. So he was subsequently offered palliative chemotherapy in form of ifosfamide and adriamycin. CT abdomen shows partial response after 3 cycles of chemotherapy according to RECIST criteria.

  13. [Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

    Science.gov (United States)

    Hiroshima, Yuki; Kaiume, Hiroko; Kirihara, Takehiko; Takeda, Wataru; Kurihara, Taro; Sato, Keijiro; Shimizu, Ikuo; Ueki, Toshimitsu; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Asano, Naoko; Watanabe, Masahide; Kobayashi, Hikaru

    2015-12-01

    A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life. PMID:26725359

  14. Inhibitiory effect of antitumor drugs on growth of gastric cancer cell in vitro%抗癌药物对体外胃癌细胞生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    艾军; 何兰欣; 梁索源; 任金荣; 段建萍

    2002-01-01

    目的探讨8种抗癌药物对体外胃癌细胞株的抑制作用.方法选用不同剂量的抗癌药物与胃癌细胞株BGC-823孵育不同时间后,用MTT法测定其细胞增长抑制率.结果 8种抗癌药物对细胞抑制率顺序:顺铂(diamminedichloroplatinum, DDP),足叶乙甙(etoposide, VP-16),5-氟脲嘧啶(5-fluorouracilum, 5-Fu),长春新碱(vincristin,VCR),阿霉素(adriamycin,ADM),丝裂霉素(mitomycin,MMC), 阿糖胞苷(arabinosylcytosine,Ara-c);对氨甲喋呤(methotrexate, MTX)不敏感.其抑制率有随药物浓度增加、作用时间延长而增高的趋势.结论 8种抗癌药物除MTX外,对BGC-823细胞均有明显的抑制作用,但存在一定差异;从本实验条件看,以中等浓度、作用 48 h 效果较为理想.

  15. Bladder preservation by internal iliac arterial infusion chemotherapy and irradiation in T3 bladder carcinoma patients over the age of 70 years

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Senji; Shintaku, Ichiro; Suzuki, Ken-ichi; Takahashi, Toshiko; Kaihou, Yasuhiro; Ishidoya, Shigeto; Namima, Takashige; Ohyama, Chikara; Orikasa, Seiichi [Tohoku Univ., Sendai (Japan). School of Medicine

    2000-12-01

    Treatment by internal iliac arterial infusion chemotherapy (IA) combined with pelvic irradiation has proved to be effective for locally invasive bladder. Eight male patients, median age of 78 years (range 73-81) were enrolled. Pretreatment CT and whole layer core biopsy revealed T3a or T3b. Pelvic CT or fine needle aspiration biopsy following bipedal lymphography revealed N0 in 4 cases, N2 in 2 and N3 in 2, respectively. Three to 7 cycles of cisplatin (CDDP) 30-50 mg/m{sup 2}, methotrexate 20 mg/m{sup 2} and tetrahydropymnyl-adriamycin 20 mg/m{sup 2} every 3 week was administered combined with 40-50 Gy of whole pelvis irradiation. In 4 renal function impaired patients, 100 mg/m{sup 2} of carboplatin was administered instead of CDDP. All patients obtained complete response and the bladders were preserved. Observation periods were from 9 to 75 months (median 37 months). One N2 patient died with metastatic disease and two died without carcinoma. Two patients developed invasive bladder cancer on the side opposite to the primary tumors. Both were successfully treated by IA and irradiation. Bladders of all except one patient functioned for a long period. Side effects of IA and irradiation were not significant. IA combined with pelvic irradiation is effective and safe for elderly patients with bladder carcinoma. (author)

  16. DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    de Wilde Rudy L

    2009-10-01

    Full Text Available Abstract Background The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics. Methods DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA hydrolysis assay. Results While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin. In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692, or did not exist for gemcitabine. Conclusion The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.

  17. Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway.

    Science.gov (United States)

    Koguchi, Tomoyuki; Tanikawa, Chizu; Mori, Jinichi; Kojima, Yoshiyuki; Matsuda, Koichi

    2016-06-01

    In response to various cellular stresses, p53 exerts its tumor suppressive effects such as apoptosis, cell cycle arrest, and senescence through the induction of its target genes. Recently, p53 was shown to control cellular homeostasis by regulating energy metabolism, glycolysis, antioxidant effect, and autophagy. However, its function in inositol synthesis was not reported. Through a microarray screening, we found that five genes related with myo-inositol metabolism were induced by p53. DNA damage enhanced intracellular myo-inositol content in HCT116 p53+/+ cells, but not in HCT116 p53-/- cells. We also indicated that inositol 3-phosphate synthase (ISYNA1) which encodes an enzyme essential for myo-inositol biosynthesis as a direct target of p53. Activated p53 regulated ISYNA1 expression through p53 response element in the seventh exon. Ectopic ISYNA1 expression increased myo-inositol levels in the cells and suppressed tumor cell growth. Knockdown of ISYNA1 caused resistance to adriamycin treatment, demonstrating the role of ISYNA1 in p53-mediated growth suppression. Furthermore, ISYNA1 expression was significantly associated with p53 mutation in bladder, breast cancer, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. Our findings revealed a novel role of p53 in myo-inositol biosynthesis which could be a potential therapeutic target. PMID:27035231

  18. Pituitary-ovarian function in breast cancer patients on adjuvant chemoimmunotherapy.

    Science.gov (United States)

    Samaan, N A; deAsis, D N; Buzdar, A U; Blumenschein, G R

    1978-06-01

    One hundred thirty-one patients with operable breast cancer were treated with adjuvant chemoimmunotherapy consisting of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG). Fifty-five of 131 patients were premenopausal of which 71% (38/55) became amenorrheic. To determine the mechanism of amenorrhea, we measured the immunoreactive serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and plasma estradiol (E2) before and after intravenous administration of luteinizing hormone-releasing hormone (LH-RH) in 11 unselected premenopausal patients who developed amenorrhea and 11 unselected patients who did not. Serum prolactin (PRL) levels were also measured before and after iv administration of thyrotropin-releasing hormone (TRH). Our results showed that patients who developed amenorrhea had abnormally high serum LH and FSH levels at basal and after LH-RH stimulation and low plasma estradiol. Serum PRL levels were normal. Patients who developed amenorrhea were older than those who did not, but their serum LH and FSH levels were also significantly higher and plasma estrogens were significantly lower than that found in 11 normal women with regular menses of the same age range. These results indicate that amenorrhea that develops in some patients with breast cancer after FAC-BCG therapy is a result of primary ovarian failure. PMID:418867

  19. Effects of the multidrug resistance modulator HZ08 on the apoptosis pathway in human chronic leukaemia cell line K562/A02.

    Science.gov (United States)

    Cen, Juan; Zhu, Yi-Lin; Yang, Yu; Zhu, Jun-Rong; Fang, Wei-Rong; Huang, Wen-Long; Li, Yun-Man; Tao, Yi-Fu

    2011-01-01

    ōancer falls to respond to chemotherapy by acquiring multidrug resistance in over 90% of patients. A previous study revealed that multidrug resistance modulator HZ08 had great multidrug resistance reversal effect in vitro and in vivo. It could enhance adriamycin (doxorubicin) induced intrinsic apoptosis pathway and rectify cell cycle and some apoptosis related proteins in human breast resistant cancer MCF-7/ADM cells. This study detected Rh123 accumulation to assess the effect of HZ08 on P-glycoprotein function in human chronic leukaemia cell line K562/A02. Moreover, mitochondria membrane potential, cytochrome c release and caspase-3 activity were analyzed for HZ08 treatment with or without vincristine. Since pretreatment with HZ08 could also reverse the multidrug resistance to vincristine in K562/A02 cells, the individual influence of HZ08 was further detected on apoptotic regulator like Bcl-2, Bax, p53, cell cycle checkpoints and proliferation regulatory factors like survivin, hTERT, c-Myc, c-Fos, c-Jun. Finally, it revealed that HZ08 increased vincristine induced activation in intrinsic apoptosis pathway by inhibition of P-gp mediated efflux. In addition, the outstanding reversal effect of HZ08 should also attribute to its individual effect on apoptosis and proliferation related regulatory factors. It renders HZ08 possibility of application in pretreatment to reverse multidrug resistance while avoiding unexpected drug interactions and accumulative toxicity. PMID:22232851

  20. Design, synthesis and evaluation of novel triazole core based P-glycoprotein-mediated multidrug resistance reversal agents.

    Science.gov (United States)

    Jiao, Lei; Qiu, Qianqian; Liu, Baomin; Zhao, Tianxiao; Huang, Wenlong; Qian, Hai

    2014-12-15

    A novel series of triazol-N-ethyl-tetrahydroisoquinoline based compounds were designed and synthesized via click chemistry. Most of the synthesized compounds showed P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) reversal activities. Among them, compound 7 with little cytotoxicity towards GES-1 cells (IC50 >80μM) and K562/A02 cells (IC50 >80μM) exhibited more potency than verapamil (VRP) on increasing anticancer drug accumulation in K562/A02 cells. Moreover, compound 7 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 7 in reversing MDR revealed that it could remarkably increase the intracellular accumulation of both rhodamine-123 (Rh123) and adriamycin (ADM) in K562/A02 cells as well as inhibit their efflux from the cells. These results suggested that compound 7 showed more potency than the classical P-gp inhibitor VRP under the same conditions, which may be a promising P-gp-mediated MDR modulator for further development. PMID:25464884

  1. Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma

    International Nuclear Information System (INIS)

    The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals

  2. Successful therapy of convoluted T-lymphoblastic lymphoma in the adult

    International Nuclear Information System (INIS)

    Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16-73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo

  3. GFP tracking transcriptional activity endogenous p53: vector construction and application in genotoxicity detection

    Institute of Scientific and Technical Information of China (English)

    ZENG Wei-sen; LUO Chen; XIE Wei-bing; CHEN Han-yuan

    2001-01-01

    To establish a sensitive.and specific system for genotoxicity detection in vivo. Methods: Endogenous p53 tracer vector p53RE was constructed by using green fluorescent protein (GFP) as a reporter to trace p53 transcriptional activity under the control of base SV40 early promoter. The tracer cells 3T3-REG were established by transfecting NIH3T3 cells with tracer vector and treated with ultraviolet, H202 and adriamycin to induce DNA damage and the subsequent endogenous p53 expression. The GFP expression and its green fluorescence in the tracer cells were observed and measured with fluorescent microscope and FACS. Results: The GFP expression increased rapidly after various treatment and reached the maximum 1 h later, and decreased gradually afterwards. FACS analysis showed that GFP expression in 3T3-REG tracer cells was consistent with the concentration of H202, while that in 3T3-SVG cells, which were transfected with control vector pSV-GFP, hardly increased in response to the treatment. Conclusion: GFP tracing p53 transcriptional activity is a sensitive and specific method for genotoxicity detection.

  4. Preclinical screening for drugs effective against 5-fluorouracil-resistant cells with a murine L5178Y cell line in vitro

    International Nuclear Information System (INIS)

    A subline of L5178Y cells has been established in vitro that exhibits a fiftyfold order of resistance to 5-fluorouracil (FUra) as compared to that of the parent line. The cytotoxic effects of 24-hour exposures to 23 antitumor drugs and to radiation were compared in the two cell lines. Four patterns of response were identified: 1) Only two drugs, mitomycin C and adriamycin, proved significantly more cytotoxic to FUra-resistant cells. 2) Four other drugs--anguidine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide, melphalan, and quelamycin--showed marginal superiority against resistant cells. 3) X-radiation and the majority of drugs tested--including 5-azacytidine, 1,3-bis(2-chloroethyl)-1-nitrosourea, cisplatin, bleomycin, dibromodulcitol, razoxane, hydroxyurea, methotrexate, teniposide, etoposide, and three experimental agents, metoprine, spirogermanium HCl, and ellipticinum--proved equally cytotoxic to both cell lines. 4) Cross-resistance with FUra was exhibited with vincristine, vindesine, pyrazofurin, and indicine-N-oxide. This experimental system provides a simple method of testing agents for activity against FUra-resistant cells before phase 1 clinical studies

  5. Appearance of febrile neutropenia episodes after cytostatic therapy on oncology patients

    International Nuclear Information System (INIS)

    Treatment of oncology patient using cytotoxic drugs has the neutropenia and its infectious complications as the commonest dose-limiting toxicity. Its appearance provokes dose delays and reduction during post-chemotherapy cycles, as well as the quality of life deterioration of patients. Oncology Medicine Group including the Pharmacy Service carried out a study to analyze the appearance of febrile neutropenia after cytotoxic therapy administration, and the presence of other factors that may to increase the risk to these reactions. A total of 42 patients were studied admitted with febrile neutropenia after above therapy from February to August, 2007. Biomedical variables from included patient group were achieved and the previously applied cytostatic therapy. The prevalent age-group was those patients aged over 50 and predominance of male sex and advanced stages with associated affections. The more frequent tumor locations were in breast, lung, and non-Hodgkin lymphoma. The cytostatic agent more used in cases of febrile neutropenia was Adriamycin (71.4 %) followed by Cyclophosphamide (52.4 %). The factors more associated with febrile neutropenia appearance were: Anthracycline chemotherapy, age over 50, advanced stages, and presence of associated diseases

  6. A Novel Use of Early Radiation Therapy in the Treatment of Hyperbilirubinemia in a Patient with Primary Hepatic Lymphoma and Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Venkata S. Tammana

    2014-01-01

    Full Text Available Lymphomas arising in the liver are extremely rare. Here, we describe a case of Hepatitis C virus infection with primary hepatic lymphoma (PHL presenting with hyperbilirubinemia. A 45-year-old African American male presented with abdominal pain, pruritus, and itching for two days. CT of abdomen and pelvis with contrast showed numerous masses in the liver. The liver biopsy was consistent with diffuse large B cell lymphoma (DLBCL. Conventional chemotherapy was avoided initially because of hyperbilirubinemia. Hence, radiation therapy was given initially to reduce his bilirubin levels and tumor size. The patient was able to complete six cycles of rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP chemotherapy and achieved a complete response verified by positron emission tomography-computed tomography (PET-CT. PHL should be considered when there are numerous space occupying liver lesions seen on imaging. Hyperbilirubinemia may be a reason for delay in treatment for some of these patients. Hence, the role of radiation therapy prior to treatment with R-CHOP is an alternative to management for stage IV diffuse large B cell lymphoma.

  7. Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature.

    Science.gov (United States)

    Yang, Qing-Xu; Pei, Xiao-Juan; Tian, Xiao-Ying; Li, Yang; Li, Zhi

    2012-01-01

    Only a few cases of extranodal Epstein-Barr virus (EBV)-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL) have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL) developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone), but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. PMID:22260632

  8. Successful treatment of mucosa-associated lymphoid tissue lymphoma in a patient with gastric and rectal lesions with metachronous and ectopic development

    Directory of Open Access Journals (Sweden)

    Hajime Umezu

    2011-04-01

    Full Text Available A 75-year-old female, who had an abnormal stomach x-ray finding, was admitted to the hospital for further examination and therapy. Upper GI endoscopy showed reddish and swollen folds on the greater curvature of the gastric body and a biopsy was of this lesion revealed malignant lymphoma (small cell type or mucosa-associated lymphoid tissue (MALT lymphoma suspected. The patient was infected with Helicobacter pylori (H. pylori, however, in response to the patient’s wishes, a total gastrectomy, omentectomy and splenectomy were performed and the histological diagnosis was gastric MALT lymphoma. Two courses of CHOP therapy (cyclophosphamide (CPM 750 mg/m2/day, day 1, adriamycin (ADM 50 mg/m2/day, day 1, vincristine sulfate (VCR 1.4 mg/m2/day, day 1, prednisolone 100 mg/body, day 1-5 were administered as adjuvant chemotherapy. A colonoscopic examination performed about 4.5 yr after the operation revealed rectal submucosal tumors and the biopsied specimens were diagnosed as malignant lymphoma. A transanal focal resection was performed and the histological diagnosis was metachronous and ectopic development of MALT lymphoma. The histological finding was similar to the gastric lesion. About 4 and 7 yr after the first development of rectal MALT lymphoma, MALT lymphomas developed repeatedly in the rectal lesion, however, these were resected repeatedly and no developmenthas occurred during the past two years. This report presents a very rare case of metachronous and ectopic MALT lymphoma de

  9. Clinical significance of I-123 MIBG myocardial scintigraphy for evaluating the severity of congestive heart failure

    International Nuclear Information System (INIS)

    We studied the significance of I-123 MIBG (metaiodobenzylguanidine) myocardial scintigraphy for evaluating the severity of congestive heart failure (CHF). I-123 MIBG scintigraphy was performed in 7 patients with CHF of NYHA class I-III (6 with dilated cardiomyopathy and 1 with adriamycine cardiomyopathy) and in 2 normals. The SPECT and anterior planar myocardial images were obtained 15 minutes after (initial images) and 4 hours after (delayed images) an injection of I-123 MIBG (111 MBq). Compared with normals, patients with CHF demonstrated (1) low myocardial uptake and (2) rapid myocardial washout of I-123 MIBG, indicating myocardial sympathetic disarrangement. Then, quantitating these abnormalities with the heart to upper mediastinum uptake ratio (H/B) and the percent washout rate (%WR) during 4 hours, respectively, we compared these two indices with LV ejection fraction (EF) at rest measured by echocardiography and exercise capacity (max VO2 and VO2 at anaerobic threshold (AT)) determined with respiratory gas exchange analysis during maximal bicycle exercise. H/B was lower and %WR was greater in patients with CHF than in normals. H/B correlated with EF (r=0.77, p2 (r=-0.74, p<0.05) and AT (r=-0.81, p<0.05). Thus, H/B and %WR were closely related to the severity of CHF. These results suggest that I-123 MIBG myocardial scintigraphy and the quantitative analysis of I-123 MIBG myocardial uptake provide useful information about the severity of CHF. (author)

  10. [Changes of sarcolemma Na+/K+ ATPase and sarcoplasmic reticulum membrane Ca2+ ATPase activity after stem cell transplantation in chronic heart failure].

    Science.gov (United States)

    Fan, Zhongcai; Chen, Mao; Deng, Juelin; Liu, Xiaojing; Zhang, Li; Rao, Li; Yang, Qing; Huang, Dejia

    2007-02-01

    To assess the changes of sarcolemma Na+/K+ ATPase (CMNKA) and sarcoplasmic reticulum membrane Ca2+ ATPase (SERCA) activities after stem cells transplantation in heart failure. Rabbit was used as heart failure model by intravenously injecting adriamycin. Autologous bone marrow mononuclear cells (BMCs), bone marrow mesenchymal stem cells (MSCs) or skeletal myoblasts (SMs) were introduced into coronary arteies through the root of aorta when two balloons occluding just above sinus of Valsalva. After 4 weeks, left ventricular ejection fraction (LVEF)was evaluated by echocardiography, and the activities of CMNKA and SERCA were measured by colorimeter. In BMCs (n=8)and MSCs (n=8) group, LVEF were significantly improved (P SMs group (n=6) compared to sham group (n=8). The CMNKA activity in all stem cells groups was significantly increased compared to sham group (P < 0.05). Meanwhile, in comparison with sham group, the incremental tendencies of SERCA activity were seen in stem cells groups. In conclusion, stem cells transplantation could increase the activities of CMNKA and SERCA in heart failure, a possible mechanism to improve heart function. PMID:17333908

  11. [Changes of heart function after different cell type stem cell transplantation in chronic heart failure].

    Science.gov (United States)

    Fan, Zhongcai; Chen, Mao; Deng, Juelin; Liu, Xiaojing; Zhang, Li; Rao, Li; Yang, Qing; Huang, Dejia

    2006-12-01

    To investigate the feasibility of introcoronary cell infusion into nonischemic heart failure (HF) heart and whether different types of stem cell transplantation would affect heart function to a similar degree. Japanese white ears rabbits were used as HF models by intravenous injection adriamycin. Autologous bone marrow mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts (SMs) or culture medium were infused into coronary arteries respectively by occluding the root of ascending aorta. The mortality during and 4 weeks after the procedure the mortality was 7.1% and 16.7% respectively. After 4 weeks, the ejection fraction (EF) in BMCs group had significant improvement (P 0.05). In sham group,the left ventricular endostolic diameter (LVED) had significant enlargement (P 0.05). Immunofluorescence revealed de novo expression of cardiac troponin I in BMCs and MSCs groups, cardiac troponin I was not detected in SMs group. In conclusions, intracoronary cell transplantation could provide effective cell delivery into dilated cardiomyopathy hearts and could be a useful strategy for treating CHF, BMCs cell transplantation may be the first choice in all the above cell types. PMID:17228727

  12. Successful treatment of HIV-associated multicentric Castleman's disease and multiple organ failure with rituximab and supportive care: a case report

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    Isaacson Peter G

    2010-01-01

    Full Text Available Abstract Introduction Multicentric Castleman's Disease (MCD, a lymphoproliferative disorder associated with Human Herpes Virus-8 (HHV-8 infection, is increasing in incidence amongst HIV patients. This condition is associated with lymphadenopathy, polyclonal gammopathy, hepato-splenomegaly and systemic symptoms. A number of small studies have demonstrated the efficacy of the anti-CD20 monoclonal antibody, rituximab, in treating this condition. Case presentation We report the case of a 46 year old Zambian woman who presented with pyrexia, diarrhoea and vomiting, confusion, lymphadenopathy, and renal failure. She rapidly developed multiple organ failure following the initiation of treatment of MCD with rituximab. Following admission to intensive care (ICU, she received prompt multi-organ support. After 21 days on the ICU she returned to the haematology medical ward, and was discharged in remission from her disease after 149 days in hospital. Conclusion Rituximab, the efficacy of which has thus far been examined predominantly in patients outside the ICU, in conjunction with extensive organ support was effective treatment for MCD with associated multiple organ failure. There is, to our knowledge, only one other published report of its successful use in an ICU setting, where it was combined with cyclophosphamide, adriamycin and prednisolone. Reports such as ours support the notion that critically unwell patients with HIV and haematological disease can benefit from intensive care.

  13. The first description of metyrapone use in severe Cushing Syndrome due to ectopic ACTH secretion in an infant with immature sacrococcygeal teratoma. Case Report.

    Science.gov (United States)

    Wojcik, Malgorzata; Kalicka-Kasperczyk, Anna; Luszawska-Kutrzeba, Teresa; Balwierz, Walentyna; Starzyk, Jerzy B

    2015-12-01

    Cushing syndrome due to ectopic secretion of ACTH in infants is rare. The treatment of choice is radical resection of the tumour in combination with pre-operative chemotherapy using steroidogenesis inhibitors if necessary. If radical surgery is not possible, palliative treatment of hypercortisolemia is recommended. The most frequently used drug in infants is ketoconazole. Experience with the use of metyrapone is poor. We report an 8-month-old female infant with congenital immature sacrococcygeal teratoma secreting AFP, beta hCG and ACTH who had undergone non-radical resection of the tumour mass and was receiving standard risk chemotherapy (vinblastine, bleomycin, and cisplatin). The infant initially presented at the age of 6 months with ACTH-dependent Cushing syndrome (cortisol and ACTH level 325 ng/mL, 112 pg/mL respectively). Treatment with ketoconazole was initiated with a dose of 600 mg/day. Due to its ineffectiveness metyrapne was added in increasing dosages, up to 1,500 mg/day. In addition the schema of chemotherapy was changed (adriamycin, bleomycin, carboplatin), which resulted in normalization of cortisol levels and blood pressure. There were no metyrapone side effects during the treatment period. We can conclude that treatment with metyrapone at a dose of 1500 mg/day might be effective and safe in infants with Cushing syndrome. PMID:26859587

  14. [High dosage chemotherapy with autologous stem cell transplantation in multiple myeloma].

    Science.gov (United States)

    Ruckser, R; Kier, P; Buxhofer, V; Kittl, E; Tatzreiter, G; Vedovelli, H; Zelenka, P; Hübl, G; Hinterberger, W

    2000-01-01

    Between 1992 and 1999 15 patients (pts.) suffering from multiple myeloma (MM) were treated with high-dose chemotherapy and consecutive autologous stem-cell transplantation (ASTx). 10/15 pts underwent two courses of ASTx (tandem- or double ASTx). So 25 ASTx were performed in these 15 pts. in total. All pts. were under 60 a. of age. 13/15 pts. received 6 cycles of chemotherapy on an average according to the VAD-protocol (Vincristin, Adriamycin, Dexamethason). Mobilisation of peripheral hematopoietic stem cells was performed with high-dose cyclophosphamide and hematopoietic growth-factors (CSFs). The conditioning protocol consisted of high-dose melphalan (200-225 mg/m2) in 24/25 ASTx. In one single case total body irradiation (TBI) plus melphalan 140 mg/m2 was used. 2/15 pts. died within 30 days from ASTx; one patient from interstitial pneumonia after TBI, and the other, who was in a very advanced stage of his disease with multiple pretreatment courses before ASTx. The overall survival (OS) was in the mean 68 months, the progression-free survival (PFS) after ASTx 21 m respectively. In pts. with MM high-dose melphalan (up to 225 mg/m2) without TBI plus ASTx is a safe and effective procedure when performed in the early course of the disease. PMID:11261278

  15. Inactivated Bone Replantation with Preservation of the Epiphysis in Children with Osteosarcoma- Clinical Report of Two Cases

    Institute of Scientific and Technical Information of China (English)

    YUXiuchun; LIUXiaoping; ZHOUYin; LIKaihua; QUZaiping

    2005-01-01

    Objective: To evaluate the value of inactivated bone replantation with preservation of the epiphysis following the effective chemotherapy in avoiding postoperative discrepancy of the affected limb in children with osteosarcoma. Methods: Two children (aged 5 and 10 years, 1 male and 1 female) with osteosarcoma underwent inactivated bone replantation with preserving epiphysis following chemotherapy (MMIA protocol, including high-dose methotrexate, adriamycin and ifosfamide). After two cycles of preoperative chemotherapy, pain vanished, the local mass shrank and there was no pain on pressing the affected parts. Sera AKP and LDH were reduced to normal levels; marked shrinkage and sclerotic changes and good margin of lesions were seen on plain radiographs and MR images. Two courses of the same protocol as preoperative chemotherapy were administered postoperatively. Results: Postoperative histological examination of the specimens demonstrated absence of vital tumor cells. Incisions healed well and no complications occurred. The replanted inactivated bone healed with host at 6 months after operation.In the two patients, no evidence was seen of metastasis and recurrence and discrepancy of the affected limbs in postoperative 36 and 48 months. Functions of the affected limbs were satisfactory. Conclusion:Inactivated bone replantation with preserving epiphysis was a viable option for osteosarcoma in children.The long-term outcomes remain to be further proven.

  16. Comparative Study on Three Chemotherapeutic Regimens for the Treatment of Advanced Epithelial Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the best first-line chemotherapy regimen for the treatment of advanced epithelial ovarian cancer (AEOC), the efficacy of three chemotherapy regimens for treatment of the patients with AEOC in our hospital during Jan. 1992- Jan. 1999 was retrospectively analyzed. The therapeutic effects were compared with the supplement of Melphalan + Hexamethylme (PAM + HMM), cisplatin + adriamycin +cyclophosphamide or isofamide (PAC) or cisplatin + cyclophosphamide or isofamide (PC), Taxol+cisplatin (TP) combined chemotherapy after cytoreductive surgery. The results showed that the overall effective rate of TP was significantly higher than that of PAM+ HMM (P<0. 05); The complete remission rate of TP was significantly higher than that of PAM+ HMM and PAC or PC (all P<0.05);The 2-year survival rate free of tumor of TP was obviously higher than that of PAM+HMM and PAC or PC(all P<0. 05). It was concluded that the therapeutic effect of TP regimen in the treatment of AEOC was better than PAM +HMM and PAC or PC and TP regimen could be recommended currently as the preferred first-line one for the treatment of AEOC.

  17. Expression of a full-length cDNA for the human MDR1 gene confers resistance to colchicine, doxorubicin, and vinblastine

    International Nuclear Information System (INIS)

    Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former generic name adriamycin) is associated with overexpression of the MDR1 gene, which encodes P-glycoprotein. The authors previously have isolated an overlapping set of cDNA clones for the human MDR1 gene from multidrug-resistant KB cells. Here they report the construction of a full-length cDNA for the human MDR1 gene and show that this reconstructed cDNA, when inserted into a retroviral expression vector containing the long terminal repeats of Moloney leukemia virus or Harvey sarcoma virus, functions in mouse NIH 3T3 and human KB cells to confer the complete multidrug-resistance phenotype. These results suggest that the human MDR1 gene may be used as a positive selectable marker to introduce genes into human cells and to transform human cells to multidrug resistance without introducing nonhuman antigens

  18. In vitro cytotoxicity studies on Carissa congesta, Polyalthia longifolia, and Benincasa hispida extracts by Sulforhodamine B assay method

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    Gaurav Mahesh Doshi

    2015-01-01

    Full Text Available Background: Indian medicinal plants have contributed to the growth of world′s ethnopharmacological heritage. Roots of Carissa congesta (CC powder are mixed with horse urine, lime juice, and camphor and used as remedies for relieving itching conditions, Polyalthia longifolia (PL leaves are aromatic and used for decoration in festivals as sonamukhi and Benincasa hispida (BH seeds provide treatment for cough and vitiated conditions of pitta. Aims of the Study: In the current studies, crude petroleum ether extracts (BH and CC and ethanolic extract of (PL were screened for in vitro cytotoxicity activity using different cell lines. Settings and Design: In the experiment, human colon cancer HCT15, human breast cancer MCF7 and human leukemia MOLT4 cell lines were studied on the extracts. Materials and Methods: The method used was Sulforhodamine B (SRB assay method in which growth inhibition of 50% (GI 50 was analyzed by comparing it with standard drug Adriamycin (ADR (doxorubicin. Results: The CC and PL extracts showed equivalent activity to ADR (doxorubicin for human breast cancer cell line MCF7 and human leukemia cell line MOLT4 respectively. BH extract did not show satisfactory activity on selected cell lines. Conclusion: In the future, new cell lines may be screened in order to check the potency of CC, PL, and BH extracts.

  19. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

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    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  20. Cardiolipin is essential for higher proton translocation activity of reconstituted Fo

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The Fo membrane domain of FoF1-ATPase complex had been purifiedfrom porcine heart mitochondria. SDS-PAGE with silver staining indicated that the purity of Fo was about 85% and the sample contained no subunits of F1-ATPase. The purified Fo was reconstituted into liposomes with different phospholipid composition, and the effect of CL (cardiolipin), PA (phosphatidic acid), PI (phosphatidylinositol) and PS (phosphatidylserine) on the H+ translocation activity of Fo was investigated. The results demonstrated that CL, PA and PI could promote the proton translocation of Fo with the order of CL>PA>>PI, while PS inhibited it. Meanwhile ADM (adriamycin) severely impaired the proton translocation activity of Fo vesicles containing CL, which suggested that CL's stimulation of the activity of reconstituted Fo might correlate with its non-bilayer propensity. After Fo was incorporated into the liposomes containing PE (phosphatidylethanolamine), DOPE (dioleoylphosphatidylethanolamine) as well as DEPE (dielaidoylphosphatidylethanolamine), it was found that the proton translocation activity of Fo vesicles increased with the increasing content of PE or DOPE, which has high propensity of forming non-bilayer structure, but was independent of DEPE. The dynamic quenching of the intrinsic fluorescence of tryptophan by HB (hypocrellin B) as well as fluorescent spectrum of acrylodan labeling Fo at cysteine indicated that CL could induce Fo to a suitable conformation resulting in higher proton translocation activity.

  1. Design, synthesis and evaluation of the multidrug resistance-reversing activity of pyridine acid esters of podophyllotoxin in human leukemia cells.

    Science.gov (United States)

    Zhang, Lei; Chen, Fan; Zhang, Zeguo; Chen, Yongzheng; Lin, Ya; Wang, Jing

    2016-09-15

    Multidrug resistance (MDR) is the main cause for chemotherapeutic failure in cancer treatment. To overcome MDR, a serious of pyridine acid esters of podophyllotoxin was synthesized and their antiproliferation activities were evaluated against two human chronic myeloid leukemia cell lines in vitro. Most of them exhibited potent growth inhibition with IC50 values in the nanomolar range as well as markedly reduced resistance factors. The most potent compound, Y8 exhibited an IC50 of 0.046±0.003μM against resistance K562/ADR cells, showing more significant than that of adriamycin and etoposide, respectively. Furthermore, Y8 efficiently triggered cell cycle arrest at S phase and simultaneously induced apoptosis in K562/ADR cells. Meanwhile, Y8 also regulated the expression levels of cell cycle- and apoptosis-related proteins. Additionally, Y8 stimulated the ERK1/2 signalling and reduced the expression of Pgp protein. Finally, on the basis of results obtained using U0126, an ERK1/2 inhibitor, the ERK1/2 signalling pathway was proposed for the multidrug resistance-reversing effect of Y8 in K562/ADR cells. Together, Y8 could be a novel potential MDR reversal agent for the treatment of drug-resistant leukemia. PMID:27503681

  2. Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance.

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    Yan Xu

    Full Text Available Multidrug resistance (MDR frequently develops in cancer patients exposed to chemotherapeutic agents and is usually brought about by over-expression of P-glycoprotein (P-gp which acts as a drug efflux pump to reduce the intracellular concentration of the drug(s. Thus, inhibiting P-gp expression might assist in overcoming MDR in cancer chemotherapy. MiRNAome profiling using next-generation sequencing identified differentially expressed microRNAs (miRs between parental K562 cells and MDR K562 cells (K562/ADM induced by adriamycin treatment. Two miRs, miR-381 and miR-495, that were strongly down-regulated in K562/ADM cells, are validated to target the 3'-UTR of the MDR1 gene. These miRs are located within a miR cluster located at chromosome region 14q32.31, and all miRs in this cluster appear to be down-regulated in K562/ADM cells. Functional analysis indicated that restoring expression of miR-381 or miR-495 in K562/ADM cells was correlated with reduced expression of the MDR1 gene and its protein product, P-gp, and increased drug uptake by the cells. Thus, we have demonstrated that changing the levels of certain miR species modulates the MDR phenotype in leukemia cells, and propose further exploration of the use of miR-based therapies to overcome MDR.

  3. Multiwavelength videomicrofluorometry for multiparametric investigations of multidrug resistance

    Science.gov (United States)

    Rocchi, Emmanuelle; Salmon, Jean-Marie; Vigo, Jean; Viallet, Pierre M.

    1996-05-01

    A major problem in the cancer chemotherapy is the development of resistance to a whole range of drugs not only similar to the drugs used for resistance induction but also to some functionally and structurally unrelated. It's one of the multifactorial causes of failure of chemotherapy. Thus it appears essential to evaluate the multi-drug resistance (MDR) in living cells populations to: detect the MDR phenotype, to discriminate between resistant and sensitive cells, to identify mechanisms which are involved in the induction or the reversion of resistance and to study the cytotoxic process. Such a challenge implies the use of multiparametric approach that has been possible using a protocol involving microfluorometry connected to numerical image analysis on single living cells. This protocol relays on the correlation existing between the decreased intracellular accumulation of some fluorescent probes such as Hoechst 33342 (Ho342) and Rhodamine 123 (R123) in resistant cells. The simultaneous estimation of the fluorescence intensities of these probes has required the use of a third probe, the Nile Red, for cell contour delineation. The analysis of parameters related to Ho342 and R123 allows the discrimination of sensitive and resistant cells. So the multiparametric approach using multi-wavelength image analysis, which appears to be a powerful technique, has allowed us to show on human lymphoblastoid CCRF-CEM cells lines that the cytotoxic effects could be different depending on the cell resistance or on the cytotoxic drug used: Adriamycine, Vinblastine and the different cell behavior could be used for cell differentiation.

  4. Does injection of metanephric mesenchymal cells improve renal function in rats?

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    Yu-qing Jiao

    2011-01-01

    Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

  5. Iatrogenic Pulmonary Nodule in a Heart Transplant Recipient

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    Atul C. Mehta

    2014-01-01

    Full Text Available A 58-year-old female with a history of non-Hodgkin lymphoma and end-stage nonischemic cardiomyopathy from Adriamycin toxicity underwent orthotic heart transplantation during June 2013. She developed shortness of breath in September 2013 and was suspected to have invasive pulmonary aspergillosis. A flexible bronchoscopy (FB with a transbronchial biopsy (TBBx was performed. She was found to have a focal lung nodule in the same location at the site of the TBBx on day 13 after the FB. Spontaneous resolution of the nodule was confirmed on the computed tomography (CT scan of chest performed at 3 months. We believe that this nodule was as a consequence of the TBBx. Formation of a peripheral pulmonary nodule (PPN following a TBBx is occasionally encountered among the recipients of the lung transplantation. To our knowledge, this is the first case of TBBx producing a pulmonary nodule in a heart transplant recipient. Physicians caring for the patients with heart transplantation should be cognizant of the iatrogenic nature of such nodule to avoid unnecessary diagnostic work-up.

  6. Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity

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    Irappa Madabhavi

    2014-01-01

    Full Text Available Hepatoblastoma (HB is a rare malignant tumour of the liver and usually occurs in the first three years of life. Hepatoblastoma in adolescents and young adults is extremely rare; nevertheless the prognosis is much worse than in childhood, because these kinds of tumours are usually diagnosed late. Characteristic imaging and histopathological and AFP levels help in the diagnosis of hepatoblastoma. Paraneoplastic features of hepatoblastoma are not uncommon at presentation and include erythrocytosis, thrombocytosis, hypocalcaemia, isosexual precocious puberty, and rarely hypoglycaemia. Even though hypoglycaemia is commonly seen in hepatocellular carcinoma, its association with hepatoblastoma is very rare. We present a case of 15-year-old male patient presenting with complaints of recurrent hypoglycaemic seizures ultimately leading to diagnosis of hepatoblastoma. Managed successfully with neoadjuvant chemotherapy, surgery and adjuvant chemotherapy with adriamycin and cisplatin based regimens. An extensive review of literature in the PubMed and MEDLINE did not reveal much data on paraneoplastic recurrent hypoglycaemic seizures as an initial presentation of hepatoblastomas in adolescents and young adults.

  7. Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

    International Nuclear Information System (INIS)

    The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C3H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

  8. Effect of dihydroxyanthraquinone (DHAQ) and radiation on the survival of cultured Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Dihydroxyanthraquinone (DHAQ) is currently being tested as a cancer chemotherapeutic agent because of its structural similarity to Adriamycin (ADR) and other DNA-intercalating antibiotics. The interaction of DHAQ and ionizing radiation on the induction of cell lethality was investigated in Chinese hamster ovary cells in culture. In asynchronous populations of cells, DHAQ produced a slight enhancement of radiation-induced cell lethality as evidenced by changes in both shoulder and slope of the radiation dose-survival curves. However, DHAQ had no effect on either the extent or time course of recovery from sublethal radiation damage. In synchronous populations of cells treated at various times before or after selection in mitosis, the combination of DHAQ and radiation produced greater cell killing than that predicted based on simple additivity of effect, with a decided enhancement for cells treated during S phase. These results indicate that DHAQ is similar to other DNA-intercalating antibiotics in regard to the interaction with ionizing radiation to produce cell lethality

  9. P-glycoprotein expression as a predictor of response to neoadjuvant chemotherapy in breast cancer

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    S Vishnukumar

    2013-01-01

    Full Text Available Background: Chemoresistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT. P-glycoprotein (P-gp expression-mediated drug efflux is one of the mechanisms responsible for multi-drug resistance. Our study was aimed to determine the role of P-gp expression as a predictor of response to NACT in locally advanced breast cancer (LABC patients. Materials and Methods: P-gp expression was performed by real-time quantitative polymerase chain reaction [qRT-PCR] in 76 patients with LABC. Response to adriamycin-based regimen was assessed both clinically and with contrast enhanced computed tomography (CECT scan before and after NACT. The significance of correlation between tumor and P-gp levels was determined with Chi-square test. Results: Twenty-one had high and 55 had low P-gp expression. On analyzing P-gp expression with response by World Health Organization (WHO criteria, statistical significance was obtained (P = 0.038. Similarly, assessment of P-gp expression with response by Response Evaluation in Solid Tumors (RECIST criteria in 48 patients showed statistical significance (P = 0.0005. Conclusion: This study proves that P-gp expression is a determinant factor in predicting response to NACT. Finally, detection of P-gp expression status before initiation of chemotherapy can be used as a predictive marker for NACT response and will also aid in avoiding the toxic side effects of NACT in non-responders.

  10. Current status, opportunities and problems in clinical combined chemoradiotherapy

    International Nuclear Information System (INIS)

    The clinical experience with combined radiation and chemotherapy has been positive in a number of situations. The enhanced local tumor control and patient cure due to the sterilization of distant metastases have been observed. More widespread clinical applications have been limited by the enhanced effects in normal tissues, necessitating radiation dose reduction which in some situations may be counterproductive. The limitations have been caused by the lack of a wide range of active anti-tumor compounds, particularly for most common solid tumors. The very active combinations of cyclophosphamide and adriamycin or cyclophosphamide and cis-Pt, as well as of the 3 agents, caused the response of a number of the solid tumors previously found to be drug resistant. The introduction of these compounds and a number of others active in slowly proliferating solid tumors will allow new look for improved survival in the tumors not yet amenable to combined radiation and chemotherapy. The experiments designed to elucidate the nature of the interaction of radiation and chemotherapy and in particular the nature of normal tissue response should allow for the safer employment of 2 modalities and should help in the design of prospective clinical trials on a more rational basis. (Yamashita, S.)

  11. Arsenic trioxide synergistically enhances radiation response in human cervical cancer cells through ROS-dependent p38 MAPK and JNK signalling pathway

    International Nuclear Information System (INIS)

    Many factors affect susceptibility of tumor cells to ionizing radiation. Among them intrinsic apoptosis sensitivity or resistancy seems to play an important role. The use of chemical modifiers as radiosensitizers in combination with low-dose irradiation may increase the therapeutic efficacy by overcoming a high apoptotic threshold. Several recent studies demonstrated additive effects of As2O3 with conventional chemotherapeutic agents such as cisplatin, adriamycin, and etoposide, but no synergism. Previously, we have shown for the first time that As2O3 sensitize human cervical cancer cells to ionizing radiation. Treatment of As2O3 in combination of ionizing radiation has synergistic effects in decreasing clonogenic survival and in the regression of tumor growth in xenografts. We also have shown that the combination treatment enhanced apoptotic cell death through a reactive oxygen species-dependent pathway in human cervical cancer cells. In this study, we investigated the regulatory mechanism of ROS-mediated mitochondrial apoptotic cell death induced by combination treatment with As2O3 and ionizing radiation in human cervical cancer cells

  12. The inhibition of DNA synthesis in vitamin-E-depleted lymphosarcoma cells by X-rays and cytostatics

    International Nuclear Information System (INIS)

    Since there is evidence that the lipid-soluble anti-oxidant vitamin E may protect the polyunsaturated fatty acids of cellular membranes from free-radical attack, a shortage of vitamin E should increase the radiosensitivity of the membranes. An investigation has been carried out into the in vivo incorporation of 3H-thymidine in spleen lymphosarcomas growing in X-irradiated (500 rad) normal and vitamin-E-deficient C57BL mice. The results showed that DNA synthesis was significantly more radiosensitive in the vitamin-E-depleted lymphosarcoma cells, and that the effect was most pronounced 3 to 5 hours post irradiation. Studied of the effects of intraperitoneal injections of the cancer therapeutic agents 1-β-D-Arabinofuranosylcytosine (ARA-C) and Adriamycin on the inhibition of thymidine incorporation into DNA showed no significant differences between normal and vitamin-E deficient lymphosarcoma cells. The inhibition of DNA synthesis by these drugs does not involve free radicals. The vitamin E deficient tumour cells had a higher lipid peroxidation rate at 370C (0.5 +- 0.1 nmoles/mg protein per hour) than the normal cells (0.2 +- 0.1 nmoles/mg protein per hour). The higher lipid peroxidation capacity corresponded with the enhanced radiosensitivity. The results provide indirect evidence for the involvement of cellular membranes in the mechanism of radiation-induced inhibition of DNA synthesis. (U.K.)

  13. Effect of sulfhydryls on potentiation of radiation-induced cell lethality by substituted anthraquinones

    International Nuclear Information System (INIS)

    The effects of various substituted anthraquinones (SAQ's) and Adriamycin (ADR) were investigated in cultured Chinese hamster V79 cells. These drugs cause a potentiation of radiation-induced cell lethality, albeit by different mechanisms. One possibility is that these components operate through the production of free radicals which then produce DNA strand breaks and crosslinks. If so, then one should be able to change the degree of cell kill by modifying sulfhydryl (SH) levels such that free radical processes are altered. Diamide, buthionine-S, R-sulfoximine, and N-ethylmaleimide (NEM) were used to reduce intracellular SH levels. Cysteamine and dithiotheitol were used to increase SH levels. In general, altered SH levels did not affect SAQ-induced cytotoxicity at low drug concentrations. When drug-tested cells were also irradiated, survival levels were generally those predicted from assuming purely additive interactions. On the other hand, survival after treatment with high concentrations of ADR and one other SAQ were decreased by concomitant treatment with NEM. Since altered SH levels do not produce changes in the potentiation of radiation-induced cell lethality by SAQs, it is concluded that free radicals are not involved in this potentiation. A free radical-mediated process may be involved in the cytotoxicity induced by ADR and other SAQs; however, it is not a simple process

  14. TATA-binding protein-related factor 2 is localized in the cytoplasm of mammalian cells and much of it migrates to the nucleus in response to genotoxic agents.

    Science.gov (United States)

    Park, Kyoung-ae; Tanaka, Yuji; Suenaga, Yusuke; Tamura, Taka-aki

    2006-10-31

    TBP (TATA-binding protein)-related factor 2 (TRF2) regulates transcription during a nuber of cellular processes. We previously demonstrated that it is localized in the cytoplasm and is translocated to the nucleus by DNA-damaging agents. However, the cytoplasmic localization of TRF2 is controversial. In this study, we reconfirmed its cytoplasmic localization in various ways and examined its nuclear migration. Stresses such as heat shock, redox agents, heavy metals, and osmotic shock did not affect localization whereas genotoxins such as methyl methanesulfonate (MMS), cisplatin, etoposide, and hydroxyurea caused it to migrate to the nucleus. Adriamycin, mitomycin C and gamma-rays had no obvious effect. We determined optimal conditions for the nuclear migration. The proportions of cells with nuclei enriched for TRF2 were 25-60% and 5-10% for stressed cells and control cells, respectively. Nuclear translocation was observed after 1 h, 4 h and 12 h for cisplatin, etoposide and MMS and hydroxyurea, respectively. The association of TRF2 with the chromatin and promoter region of the proliferating cell nuclear antigen (PCNA) gene, a putative target of TRF2, was increased by MMS treatment. Thus TRF2 may be involved in genotoxin-induced transcriptional regulation. PMID:17085973

  15. Tumor cell heterogeneity: impact on mechanisms of therapeutic drug resistance

    International Nuclear Information System (INIS)

    Purpose: The aim of these studies was to determine whether chemotherapy-resistant tumor cell sublines derived from a single starting cell population with identical treatment protocols, have the same mechanism of resistance. Methods and Materials: Twelve cyclophosphamide-resistant sublines were derived from KHT-iv murine sarcoma cells by repeated exposures to 2, 4, or 8 μg/ml doses of 4-hydroperoxycyclophosphamide (4-OOHCP). To investigate possible mechanisms of resistance, glutathione (GSH) levels, glutathione S-transferase (GST) activity, and aldehyde dehydrogenase (ALDH) activity were determined. In addition, studies with the GSH depletor buthionine sulfoximine (BSO) and the ALDH inhibitor diethylamino-benzaldehyde (DEAB) were undertaken. Results: Resistant factors to 4-OOHCP, assessed at 10% clonogenic cell survival, ranged from 1.5-7.0 for the various cell lines. Crossresistance to melphalan and adriamycin also were commonly observed. Increased GSH levels, GST activity and ALDH activity were detected in the sublines but not all exhibited the same pattern of biochemical alterations. The response to GSH and ALDH inhibitors also varied among the sublines; the resistance being reversible in some cell lines but not others. Conclusion: The present results indicate that when resistant sublines are derived simultaneously from the same starting cell population, the observed mechanisms of resistance may not be the same in each of the variants. These findings support the hypothesis that preexisting cellular heterogeneity may affect mechanisms of acquired resistance

  16. Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors.

    Science.gov (United States)

    Wu, Yuxiang; Pan, Miaobo; Dai, Yuxuan; Liu, Baomin; Cui, Jian; Shi, Wei; Qiu, Qianqian; Huang, Wenlong; Qian, Hai

    2016-05-15

    A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. PMID:27073052

  17. Venezenin: a new bioactive Annonaceous acetogenin from the bark of Xylopia aromatica.

    Science.gov (United States)

    Colman-Saizarbitoria, T; Gu, Z M; Zhao, G X; Zeng, L; Kozlowski, J F; McLaughlin, J L

    1995-04-01

    Asimicin and a new cytotoxic Annonaceous acetogenin, venezenin [1], were isolated from the bark of Xylopia aromatica by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 represents an unusual type of C37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings and possessing a double bond located two methylenes away from a vicinal diol in the hydrocarbon chain. The structure of 1 was elucidated by 1H- and 13C-nmr, COSY, single-relayed COSY, and by HMBC techniques, and derivatization. Annomontacin 10-one [6] and 18/21-cis-annomontacin-10-one [7], two semi-synthetic mono-THF acetogenins were prepared from 1. These acetogenins showed cytotoxicity, comparable or superior to adriamycin, against three human solid tumor cell lines. Reduction of the 10-keto of 1 to the racemic OH-10 derivative enhanced the bioactivity, as did the conversion of 1 to 6 and 7. Venezenin [1], like other Annonaceous acetogenins, showed inhibition of oxygen uptake by rat liver mitochondria and demonstrated that the THF ring may not be essential to this mode of action. PMID:7623031

  18. Multiwavelength videomicrofluorimetric method for a preliminary, fast, and inexpensive screening of the cytoxic properties of new drugs: application to some new marine peptides

    Science.gov (United States)

    Viallet, Pierre M.; Rocchi, Emmanuelle; Vigo, Jean; Salmon, Jean-Marie

    1999-07-01

    The discovery of new families of active drugs isolated from natural sources is an appealing avenue to avoid the MDR consequences in cancer treatment. Unfortunately the procedures of isolation and purification of these compounds are generally complex and time-consuming so that only tiny amounts of the new drugs are available for the preliminary biological tests. As a consequence there is a need for reliable, quantitative methods, more informative than the conventional cytotoxicity curve on the potential intracellular targets, and for which only tiny amounts of drugs are necessary. We have recently developed a method of screening based on a triple labeling process of single living cells in culture, involving the simultaneous use of Hoechst 33342 for nuclear staining. Rhodamine 123 for mitochondrial staining and Nile Red for cell delineation. Numerical image analysis was used to study both the dose- effect and the time-effect of well-known cytotoxic drugs such adriamycin, allowing to select the more informative biochemical parameters. The use of this method has recently been extended to new marine peptides such as didemnin B and some laxaphycins.

  19. Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents.

    Science.gov (United States)

    Bi, Chongwen; Ye, Cheng; Li, Yinghong; Zhao, Wuli; Shao, Rongguang; Song, Danqing

    2016-05-01

    Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells. PMID:27175333

  20. Local recurrence, rate and sites of metastases, and time to relapse as a function of treatment regimen, size of primary and surgical history in 62 patients presenting with non-metastatic Ewing's sarcoma of the pelvic bones

    International Nuclear Information System (INIS)

    This report reviews the experience of 62 patients who presented between 1972 and 1978 with non-metastatic Ewing's sarcoma of the pelvis and were entered on IESS I. Seventeen patients (27%) developed a local recurrence, 38 patients (61%) demonstrated metastases and 21 (34%) neither. In the dose range 4000 rad to 6000 rad no dose response could be detected for local control of tumor. Forty-six patients (74%) had a biopsy or exploratory surgery only, 5 patients (8%) had an incomplete resection and 11 patients (18%) has a complete resection of their tumor. In the 46 patients having a biopsy only, 13 developed a local recurrence (28%) as compared to 2 of 11 patients undergoing a complete resection (18%). The most common sites for metastases were lung in 19 patients (31%) and bone in 23 patients (37%). No significant difference was noted in the frequency of overall metastases or metastases to any site between those patients receiving one of the three treatment regimens used in IESS I: VAC and Adriamycin (regime I), VAC alone (regimen II) and VAC plus bilateral pulmonary irradiation (regimen III). At a median follow-up of 135 weeks no significant difference in median survival could be detected in patients with pelvic primaries between regimens I, II and III. The possible reasons for the poor prognosis of pelvic primary patients are discussed together with treatment policies that might improve the survival of this group of patients

  1. Effect of treatment in fractionated schedules with the combination of x-irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin

    International Nuclear Information System (INIS)

    RIF-1 tumors, implanted syngeneically in the gastrocnemius muscles of the right hind legs of C3H/Km mice, were treated either with X ray alone, drug alone, or drug and X ray combined. The drugs tested were bleomycin, BCNU, cis-diamminedichloro platinum, adriamycin, cyclophosphamide, and actinomycin-D. All drugs were administered either in the maximum tolerated dose or a dose that causes minimal tumor growth delay. Both drugs and X rays were administered either as a single dose or in five daily fractions. In addition to the single modality controls, seven different schedules of combined modalities were tested. Tumors were measured periodically after treatment in order that the day at which each tumor reached 4 times its initial cross-sectional area, i.e., its size at the time of treatment, could be determined. The effect of treatment on tumors was based upon excess growth delay (GD), i.e., T400% (treated)-T400% (untreated control). Treatment effects for the same combined modality schedules were also determined for normal skin, using the early skin reaction as an endpoint. Dose effect factors (DEF) were computed for all combined modality schedules and were based upon calculated radiation dose equivalents. We also calculated supra-additivity ratios, SR/sub I/ and SR/sub II/, therapeutic gain factors and adjusted therapeutic gain factors. The only drugs to produce significant supra-additivity with X rays were cis-Pt and cyclo

  2. A case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration successfully treated with antitumor and immunotherapy.

    Science.gov (United States)

    Tsuboguchi, Shintaro; Yajima, Ryuji; Higuchi, You; Ishikawa, Masanori; Kawachi, Izumi; Koyama, Yu; Nishizawa, Masatoyo

    2016-07-28

    We report a case of slowly progressive anti-Yo-associated paraneoplastic cerebellar degeneration (PCD) with breast cancer in a 54-year-old woman. The symptoms of limb and truncal ataxia, and dysarthria gradually progressed during the course of 1 year, and the modified Rankin scale (mRS) score was 2. A mastectomy with sentinel lymph node resection was performed for the breast cancer. No malignant cells were found on histopathological examination of the lymph node. Combination chemotherapy with adriamycin and cyclophosphamide (AC) prevented neurologic deterioration. However, subsequent treatment with trastuzumab and paclitaxel did not prevent progression of the symptoms (mRS score 3). Brain magnetic resonance imaging showed atrophy of the cerebellar hemispheres without brain stem atrophy. Anti-Yo antibody was detected in the serum, which led to a diagnosis of anti-Yo-associated PCD. We resected an enlarged axillary lymph node, which was found on computed tomography. The histopathological analysis of the lymph node revealed foreign body granuloma, which suggested an association with necrotic malignant tissue. Following additional tegafur-uracil therapy and two courses of intravenous immunoglobulin (IVIg), the cerebellar signs and symptoms gradually improved (mRS score 2). The clinical course shows that PCD can present as a slowly progressive cerebellar symptom. We propose an active treatment for anti-Yo-associated PCD consisting of tumor resection, combined chemotherapy, and IVIg. PMID:27356731

  3. Interventional radiology in the cancer patient

    International Nuclear Information System (INIS)

    The contributions of the interventional radiologist in the diagnosis and management of the cancer patient include angiography and intraarterial CT-angiography, intraarterial infusion therapy, embolization, chemoembolization, biopsy and drainage procedures, central venous catheter reposition and retrieval, and stent dilation of stenotic tubular structures in the following organ systems: (1) Kidney. Arterial embolization, therapeutic delay, enphrectomy, and medroxyprogesterone yield a response rate of 28% in patients with renal cell carcinoma and pulmonary parenchymal metastases. (2) Liver. The carcinoid syndrome secondary to hepatic metastases can be controlled by embolization in 87% of patients. Islet cell carcinoma of the pancreas with hepatic metastases is successfully managed in 75% of patients. Chemoembolization (Ivalon and cisplatin) has been effective in 60% of patients with hepatic metastases from ocular melanoma. (3) Bone. A 73% 3-year survival rate is now possible with the inraarterial infusion of cisplatin, while Adriamycin is given intravenously in patients with osteosarcoma. Limb salvage is now possible in 80% of cases. Cancers of the vulva, vagina, urethra, and penis have been successfully treated with intraarterial infusion of chemotherapy followed by radiation therapy. (5) An expansile metallic stent is available to alleviate obstructions of the vena cava, the aorta and its major branches, the tracheobronchial tree, and the common duct. These techniques are demonstrated and results discussed

  4. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Shih-Chiang Lin

    2013-01-01

    Full Text Available To compare the outcomes of melphalan 200 mg/m2 (HDM200 and 8 Gy total marrow irradiation (TMI delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy in newly diagnosed symptomatic multiple myeloma (MM Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP. In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P=0.048. However, hematologic recovery (except for neutrophils, transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P=0.387. As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200.

  5. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  6. Ewing’s sarcoma: an uncommon breast tumor

    Directory of Open Access Journals (Sweden)

    Sawsen Meddeb

    2014-10-01

    Full Text Available Ewing’s sarcoma/primitive neuroectodermal tumors (EWS/PNET are rare malignant and aggressive tumors, usually seen in the trunk and lower limbs of children and young adults. They are uncommon in the breast. We report a case of a 43-year-old woman who developed a painless breast mass. An initial core needle biopsy concluded to a fibrocystic dystrophy contrasting with a rapidly growing mass; thus a large lumpectomy was done. Diagnosis of primary PNET of the breast was established, based on both histopathological examination and immunohistochemical findings. Surgical margins were positive, therefore, left modified radical mastectomy with axillary lymph nodes dissection was performed. The patient was given 6 cycles of adjuvant chemotherapy containing cyclophosphamide, adriamycin and vincristine. Twenty months later, she is in life without recurrence or metastasis. EWS/PNET may impose a diagnostic challenge. Indeed, mammography and ultrasonography features are non specific. The histopathological pattern is variable depending on the degree of neuroectodermal differentiation. Immuno-phenotyping is necessary and genetic study is the only confirmatory tool of diagnosis showing a characteristic cytogenetic anomaly; t (11; 22 translocation.

  7. Synthesis and biological evaluation of D-ring fused 1,2,3-thiadiazole dehydroepiandrosterone derivatives as antitumor agents.

    Science.gov (United States)

    Cui, Hai-Wei; Peng, Shihong; Gu, Xiang-Zhong; Chen, Huang; He, Yuan; Gao, Wei; Lv, Fang; Wang, Jin-Hua; Wang, Yan; Xie, Jia; Liu, Ming-Yao; Yi, Zhengfang; Qiu, Wen-Wei

    2016-03-23

    A series of D-ring fused 1,2,3-thiadiazole DHEA derivatives were synthesized and investigated for their activity against the growth of various tumor cell lines using the sulforhodamine B (SRB) assay. It is amazing that for these compounds, T47D cell line was much more sensitive than other tumor cell lines. The most potent saturated N-heterocyclic derivatives showed similar antitumor effect with the positive control compound ADM (adriamycin) on T47D cells, that was 44-60 folds more potent than the lead compound DHEA. Most compounds with potent antitumor activity displayed low toxicity on normal human fibroblasts (HAF). Especially compound 25 (CH33) showed an IC50 of 0.058 μM on T47D cells and its selectivity index (SI) between HAF and T47D was 364, which was 214 folds better than ADM (SI = 1.7). The apoptosis, colony formation and transwell migration assays of 25 were performed on T47D cell line. The primary mechanism study showed that 25 caused a dose-dependent induction of apoptosis, and induced phosphorylation of EphA2 and EphB3 in T47D cells. The in vivo antitumor effect of 25 was also observed in T47D tumor-bearing mice without obvious toxicity. PMID:26866967

  8. Chemotherapy combined with involved-field radiotherapy for 177 children with Hodgkin's disease treated in 1983-1987

    International Nuclear Information System (INIS)

    During the period from 1983 through 1987, a total of 177 children with biopsy proven Hodgkin's disease have undergone chemotherapy combined with local irradiation. The patients were divided into low, middle, and high stage groups. MVPP chemotherapy, consisting of mechlorethamine, vinblastine, procarbazine, and prednisone, was given as the basic treatment. B-DOPA chemotherapy, consisting of bleomycin, dacarbazine, vincristine, prednisone, and adriamycin, was given to some children. Irradiation was limited to involved regions by cobalt therapy for 114 patients and by conventional radiotherapy for 56 patients. In the remaining 7 patients, radiotherapy was given to peripheral lymph nodes and cobalt therapy to mediastinal tumor and/or abdomen. Irradiation doses ranged from 30 to 40 Gy in most of the patients. One hundred and seventy five patients (98.9%) had complete remission (CR). The probability for 5-year disease-free survival and survival was 0.91 and 0.98, respectively. The most common hematological complication was leukopenia. Relapse occurred in a total of 15 patients (8.5%) within 4-48 months after establishing the first CR: it was the most frequent in the middle stage group (8 patients). Seven patients died: 4 died as a result of complications and the other 3 died during the first CR. (N.K.)

  9. La Autoantigen Induces Ribosome Binding Protein 1 (RRBP1) Expression through Internal Ribosome Entry Site (IRES)-Mediated Translation during Cellular Stress Condition.

    Science.gov (United States)

    Gao, Wenqing; Li, Qi; Zhu, Ruiyu; Jin, Jian

    2016-01-01

    The function of ribosome binding protein 1 (RRBP1) is regulating the transportation and secretion of some intracellular proteins in mammalian cells. Transcription of RRBP1 is induced by various cytokines. However, few studies focused on the process of RRPB1 mRNA translation. The RRBP1 mRNA has a long 5' untranslated region that potentially formed a stable secondary structure. In this study, we show that the 5' UTR of RRBP1 mRNA contains an internal ribosome entry site (IRES). Moreover, the RRBP1 expression is induced by chemotherapeutic drug paclitaxel or adriamycin in human hepatocellular carcinoma cells and accompanied with the increased expression of La autoantigen (La), which binds to RRBP1 IRES element and facilitates translation initiation. Interestingly, we found IRES-mediated RRBP1 translation is also activated during serum-starvation condition which can induce cytoplasmic localization of La. After mapping the entire RRBP1 5' UTR, we determine the core IRES activity is located between nt-237 and -58. Furthermore, two apical GARR loops within the functional RRBP1 IRES elements may be important for La binding. These results strongly suggest an important role for IRES-dependent translation of RRBP1 mRNA in hepatocellular carcinoma cells during cellular stress conditions. PMID:27447629

  10. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma

    International Nuclear Information System (INIS)

    To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting. (orig.)

  11. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Barrington, Sally F.; Somer, Edward J.; O' Doherty, Michael J. [Kings College London Division of Imaging, PET Imaging Centre at St Thomas' , London (United Kingdom); Qian, Wendi [MRC Clinical Trials Unit, London (United Kingdom); Franceschetto, Antonella; Bagni, Bruno [University of Modena and Reggio Emilia, Department of Nuclear Medicine, Modena (Italy); Brun, Eva; Almquist, Helen [Lund University Hospital, Departments of Oncology and Clinical Physiology, Lund (Sweden); Loft, Annika; Hoejgaard, Liselotte [Copenhagen University Hospital, PET and Cyclotron Unit, Rigshospitalet, Copenhagen (Denmark); Federico, Massimo [University of Modena and Reggio Emilia, Department of Haematology and Oncology, Modena (Italy); Gallamini, Andrea [Azienda Ospedaliera S. Croce e Carle, Hematology Department, Cuneo (Italy); Smith, Paul [Cancer Research UK and UCL Cancer Trials Centre, London (United Kingdom); Johnson, Peter [Cancer Research UK Clinical Centre, Southampton (United Kingdom); Radford, John [The Christie NHS Foundation Trust and the University of Manchester, Manchester (United Kingdom)

    2010-10-15

    To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries. Four centres reported scans from 50 patients with stage II-IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using 'normal' mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading). There was agreement that the response scan was 'positive' or 'negative' for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74-0.96) for conservative reading and 0.79 (95% CI 0.67-0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively. The criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting. (orig.)

  12. Downregulation of Rap1 promotes 5-fluorouracil-induced apoptosis in hepatocellular carcinoma cell line HepG2.

    Science.gov (United States)

    Zha, Yong; Gan, Ping; Yao, Qian; Ran, Feng-Ming; Tan, Jing

    2014-04-01

    Recent studies have revealed that repressor/activator protein (Rap1) not only protects telomeres from sister chromatid exchange, but also functions in genomewide transcriptional regulation. Knockdown of Rap1 sensitizes breast cancer cells to adriamycin-induced apoptosis. However, little is known about the role of Rap1 in the progression of hepatocellular carcinoma (HCC). The present study aimed to investigate the functions of Rap1 in HCC progression and to determine whether targeting the Rap1 signaling pathway may be of therapeutic value against HCC. We found knockdown of Rap1 by microRNA (miRNA) interference enhanced significantly apoptosis and 5-fluorouracil (5-FU) chemosensitivity in HepG2 cell line. Rap1 miRNA downregulated nuclear factor-κB p65 (NF-κB p65) expression, and upregulated inhibitor of NF-κB (IκB) expression. In vivo, Rap1 miRNA combined with 5-FU treatment led to a significant reduction of tumor growth as compared with 5-FU alone. The results indicate that Rap1 miRNA can effectively enhance sensitivity of HepG2 cell line to 5-FU chemotherapy in vitro and in vivo. PMID:24549317

  13. Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase π gene

    International Nuclear Information System (INIS)

    Recent studies have suggested that glutathione S-transferase π (GST-π) may play a role in determining tumor sensitivities to cytotoxic drugs. In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-π cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers. Modestly increased resistance of the GST-π transfectants preferentially to sublethal damage caused by ionizing radiation as well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were virtually unaltered. These results suggest that GST-π may not play a major role in chemo- and radioresistance of lung cancers, although it could afford selective and limited protection against ADM- and ionizing radiation-induced damage. (author)

  14. Randomized trial of combined modality therapy of childhood non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    From 1975 to 1978, 69 children with non-Hodgkin's lymphoma were staged and treated in a randomized protocol to determine the contribution of involved-field radiotherapy (IF-RT) to an effective drug regimen in Stages III to IV and the efficacy of prophylactic treatment of the central nervous system with cranial irradiation and intrathecal methotrexate in Stages II to IV. Induction therapy for Stages I to II was vincristine, prednisone, cyclophosphamide and IF-RT (3000 to 3500 rad). Stages III to IV received the same three drugs plus adriamycin, and were randomized to receive or not receive IF-RT. The complete remission rate was 88%. After randomization to receive CNS prophylaxis or not, all children received oral mercaptopurine and methotrexate for 18 months. The two-year actuarial estimate of disease-free survival for all responders is 55% and is significantly influenced by stage. (Ninety percent disease-free survival for Stages I to II, versus 38.8% for III to IV, P < 05). We observed no benefit but added toxicity from IF-RT in Stages III to IV. Efforts at CNS prophylaxis in high-risk children are warranted, since only 1 of 18 children randomized to receive prophylaxis developed CNS disease as the site of first relapse, whereas 4 of 16 receiving no prophylaxis did so

  15. Radiation induction of drug resistance in RIF-1 tumors and tumor cells

    International Nuclear Information System (INIS)

    The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

  16. Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

    International Nuclear Information System (INIS)

    The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors

  17. 盐酸千金藤碱逆转K562/ADR细胞多药耐药性及其机制%Correlation between reversing effect of cepharanthine hydrochloride on multidrug resistance and P-glycoprotein expression and function of K562/ADR cells

    Institute of Scientific and Technical Information of China (English)

    彭有梅; 王宁; 王亚峰; 韩立; 张艳; 江金花; 周玉冰; 王庆端

    2012-01-01

    研究盐酸千金藤碱(cepharanthine hydrochloride,CH)逆转K562/ADR细胞多药耐药性及其机制.采用MTT法检测多柔比星(adriamycin,ADR)单用及分别与CH、维拉帕米(verapamil,VER)合用的细胞毒作用;采用流式细胞仪,测定CH对细胞内ADR蓄积、罗丹明123 (Rho123)蓄积和泵出及P糖蛋白(P-gp)表达的影响.结果表明,CH(4 μmol·L-1)使K562/ADR细胞对ADR的敏感性增加7.43倍,逆转活性是VER的3.19倍,但对K562敏感株基本无影响.同时CH浓度依赖性地增加K562/ADR细胞内ADR和Rho123的蓄积,减少Rho123的泵出,抑制P糖蛋白的表达,但对K562细胞均无明显影响.CH在体外逆转肿瘤细胞多药耐药性的作用可能与其抑制P糖蛋白的功能和表达有关.%In this study, cepharanthine hydrochloride (CH) was tested for its potential ability to modulate the expression and function of P-glycoprotein (P-gp) in the multidmg-resistant human chronic myelogenous leukemia cell line K562/ADR. Cytotoxicity of adriamycin (ADR) alone or in combination with CH or verapamil (VER) in K562 and K562/ADR cells was determined by MTT assay. Based on flow cytometric technology, the effect of CH or VER on the uptake and efflux of rhodaminel23 (Rhol23) and the accumulation of ADR in these cells was detected by measuring Rhol23 or ADR-associated mean fluorescence intensity (MFI). The effects of CH and VER on P-glycoprotein (P-gp) expression in K562 and K562/ADR cells were also measured using a flow cytometry with PE-conjugated P-glycoprotein antibody. The results show that CH significantly enhanced the sensitivity of K562/ADR cells to ADR, 4 μmol·L"1 of CH enhanced the sensitivity of K562/ADR cells to ADR by 7.43 folds, the reversal activity was 3.19 times higher than that of verapamil. However, CH had no effect on drug-sensitive K562 cells (P < 0.05). CH increased Rhol23 and ADR accumulation in a concentration-dependent manner (2-8 umol·L-1) and inhibited the efflux of Rhol23 from these cells, but

  18. Cardiolipin is essential for higher proton translocation activity of reconstituted Fo

    Institute of Scientific and Technical Information of China (English)

    YANG; Hui

    2001-01-01

    .[12] Collinson, I. R., Runswick, M. J., Buchanan, S. K. et al., Fo Membrane domain of ATP synthase from bovine heart mitochondria: Purification, subunit composition and reconstitution with F1-ATPase, Biochemistry, 1994, 33: 7971.[13] Goormaghtigh, E., Chatelain, P., Caspers, J. et al., Evidence of a specific complex between adriamycin and negatively-charged phospholipids, Biochim. Biophys. Acta, 1980, 597: 1.[14] Goormaghtigh, E., Vandenbranden, M., Ruysschaert, J. M. et al., Adriamycin inhibits the formation of non-bilayer lipid structures in cardiolipin-containing model membranes, Biochim. Biophys. Acta, 1982, 685: 137.[15] Walker,J.E.,Lutter,R.,Dupuis,a.et al.,Identification of the subunits of F1F0-ATPase from bovine heart mitochondria,Biochemistry,1991,30:5369.

  19. Phytochemical screening and antioxidant, antimitotic, and antiproliferative activities of Trichodesma indicum shoot

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    Shweta S Saboo

    2014-01-01

    Full Text Available Background: Traditionally Trichodesma indicum has been used for its therapeutic effect in folk medicine that include anti-inflammatory, analgesic and anticancer properties. In this work, we validate the anticancer potential of the plant. Aims: To screen the shoot extracts T. indicum for their antimitotic and antiproliferative activities. Materials and Methods: The dried aerial parts of T. indicum were successively extracted with petroleum ether, successive chloroform extract (SCH, successive ethanol extract (SEE and water. The plant extracts were subjected to study of in vitro antioxidant activity using 2,2′- diphenyl-1-picrylhydrazyl, 2,2′- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radical inhibition systems. The extracts were also tested for their in vitro antimitotic activity in Allium cepa root and antiproliferative activity using the yeast model and five human cell lines (MCF-7, HOP-62, MOLT-4, HCT-15 and PRO. Result and Conclusion: The mitotic index for SCH and SEE was found to be 12.01 ± 1.34 and 12.99 ± 0.25 mg/mL, respectively. The IC 50 value in the antiproliferative assay was found to be 30.14-35.36 mg/mL for SCH and SEE respectively. Both SCH and SEE extracts showed significant antimitotic and antiproliferative activity when compared to the standard methothreaxate, vincreastine and adriamycin. Among the extracts, SEE showed strong inhibition against MCF-7 and MOLT-4 cell lines at concentration <30 μg/mL. Phytochemical analysis of extracts indicated the presence of β-sitosterol, gallic acid and catechin. Based on these results, it is concluded that T. indicum may be a good candidate for the treatment of a variety of cancer. Thus, its traditional use is validated.

  20. Factors influencing caries incidence in permanent teeth in children/adolescents under and after anti-neoplastic treatment

    Science.gov (United States)

    Brożyna, Agnieszka; Dembowska-Bagińska, Bożenna; Olczak-Kowalczyk, Dorota

    2016-01-01

    Aim of the study To determine reasons for the increase in caries among children/adolescents treated for neoplasms. Material and methods Health promoting behaviour, oral hygiene (PLI), gingiva (GI), dentition (DMFt/DMFs), number of teeth with white spot lesions (WSL), and enamel defects (ED) were assessed in three groups of 60 patients each. The three groups were as follows: under chemotherapy (CH), after chemotherapy (PCH), and generally healthy (CG). Medical files supplied information on neoplasm type, chemotherapeutic type and dose, age at treatment start, chemotherapy duration, and complications. Statistical analysis was performed with Mann-Whitney U test and Spearman's rho test. Results The age at which chemotherapy was started/its duration was 5.9 ±4.0/1.3 ±0.5 years in PCH and 9.12 ±4.44/0.8 ±0.3 years in CH; PCH completed treatment 4.9 ±3.4 years ago. Chemotherapy most often included vincristine (VCR), etoposide (VP-16), adriamycin (ADM), cyclophosphamide (CTX), cisplatin (CDDP), and ifosphamide (IF). Mucositis occurrence was 28.33% in PCH and 45.00% in CH; vomiting occurrence was 43.33% and 50.00%, respectively. Nutrition and prophylaxis mistakes occurred more often in CH/PCH than in CG; PLI, GI, caries incidence and severity, and the number of teeth with WSL were higher. Correlation between caries incidence and chemotherapeutic type and dose, age at treatment start and treatment duration, mucositis, emesis, PLI, GI, ED, no fluoride prophylaxis, and nutritional mistakes was established. Ifosphamide and mucositis treatment played a major role in chemotherapy; after chemotherapy – ED and CTX, ADM, IF, and VP-16. Conclusions Caries in permanent teeth in children/adolescents undergoing chemotherapy result from nutritional mistakes, poor prophylaxis, and indirectly from chemotherapy complications (first mucositis and emesis, and later developmental ED). PMID:27095939

  1. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    International Nuclear Information System (INIS)

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer

  2. Targeting tubulointerstitial remodeling in proteinuric nephropathy in rats

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    Saleh Yazdani

    2015-08-01

    Full Text Available Proteinuria is an important cause of tubulointerstitial damage. Anti-proteinuric interventions are not always successful, and residual proteinuria often leads to renal failure. This indicates the need for additional treatment modalities by targeting the harmful downstream consequences of proteinuria. We previously showed that proteinuria triggers renal lymphangiogenesis before the onset of interstitial inflammation and fibrosis. However, the interrelationship of these interstitial events in proteinuria is not yet clear. To this end, we specifically blocked lymphangiogenesis (anti-VEGFR3 antibody, monocyte/macrophage influx (clodronate liposomes or lymphocyte and myofibroblast influx (S1P agonist FTY720 separately in a rat model to investigate the role and the possible interaction of each of these phenomena in tubulointerstitial remodeling in proteinuric nephropathy. Proteinuria was induced in 3-month old male Wistar rats by adriamycin injection. After 6 weeks, when proteinuria has developed, rats were treated for another 6 weeks by anti-VEGFR3 antibody, clodronate liposomes or FTY720 up to week 12. In proteinuric rats, lymphangiogenesis, influx of macrophages, T cells and myofibroblasts, and collagen III deposition and interstitial fibrosis significantly increased at week 12 vs week 6. Anti-VEGFR3 antibody prevented lymphangiogenesis in proteinuric rats, however, without significant effects on inflammatory and fibrotic markers or proteinuria. Clodronate liposomes inhibited macrophage influx and partly reduced myofibroblast expression; however, neither significantly prevented the development of lymphangiogenesis, nor fibrotic markers and proteinuria. FTY720 prevented myofibroblast accumulation, T-cell influx and interstitial fibrosis, and partially reduced macrophage number and proteinuria; however, it did not significantly influence lymphangiogenesis and collagen III deposition. This study showed that proteinuria-induced interstitial

  3. Targeting tubulointerstitial remodeling in proteinuric nephropathy in rats.

    Science.gov (United States)

    Yazdani, Saleh; Hijmans, Ryanne S; Poosti, Fariba; Dam, Wendy; Navis, Gerjan; van Goor, Harry; van den Born, Jacob

    2015-08-01

    Proteinuria is an important cause of tubulointerstitial damage. Anti-proteinuric interventions are not always successful, and residual proteinuria often leads to renal failure. This indicates the need for additional treatment modalities by targeting the harmful downstream consequences of proteinuria. We previously showed that proteinuria triggers renal lymphangiogenesis before the onset of interstitial inflammation and fibrosis. However, the interrelationship of these interstitial events in proteinuria is not yet clear. To this end, we specifically blocked lymphangiogenesis (anti-VEGFR3 antibody), monocyte/macrophage influx (clodronate liposomes) or lymphocyte and myofibroblast influx (S1P agonist FTY720) separately in a rat model to investigate the role and the possible interaction of each of these phenomena in tubulointerstitial remodeling in proteinuric nephropathy. Proteinuria was induced in 3-month old male Wistar rats by adriamycin injection. After 6 weeks, when proteinuria has developed, rats were treated for another 6 weeks by anti-VEGFR3 antibody, clodronate liposomes or FTY720 up to week 12. In proteinuric rats, lymphangiogenesis, influx of macrophages, T cells and myofibroblasts, and collagen III deposition and interstitial fibrosis significantly increased at week 12 vs week 6. Anti-VEGFR3 antibody prevented lymphangiogenesis in proteinuric rats, however, without significant effects on inflammatory and fibrotic markers or proteinuria. Clodronate liposomes inhibited macrophage influx and partly reduced myofibroblast expression; however, neither significantly prevented the development of lymphangiogenesis, nor fibrotic markers and proteinuria. FTY720 prevented myofibroblast accumulation, T-cell influx and interstitial fibrosis, and partially reduced macrophage number and proteinuria; however, it did not significantly influence lymphangiogenesis and collagen III deposition. This study showed that proteinuria-induced interstitial fibrosis cannot be

  4. Glutathione Depletion Induced by c-Myc Downregulation Triggers Apoptosis on Treatment with Alkylating Agents

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    Annamaria Biroccio

    2004-05-01

    Full Text Available Here we investigate the mechanism(s involved in the c-Myc-dependent drug response of melanoma cells. By using three M14-derived c-Myc low-expressing clones, we demonstrate that alkylating agents, cisplatin and melphalan, trigger apoptosis in the c-Myc antisense transfectants, but not in the parental line. On the contrary, topoisomerase inhibitors, adriamycin and camptothecin, induce apoptosis to the same extent regardless of c-Myc expression. Because we previously demonstrated that c-Myc downregulation decreases glutathione (GSH content, we evaluated the role of GSH in the apoptosis induced by the different drugs. In control cells treated with one of the alkylating agents or the others, GSH depletion achieved by L-buthionine-sulfoximine preincubation opens the apoptotic pathway. The apoptosis proceeded through early Bax relocalization, cytochrome c release, concomitant caspase-9 activation, whereas reactive oxygen species production and alteration of mitochondria membrane potential were late events. That GSH was determining in the c-Myc-dependent druginduced apoptosis was demonstrated by altering the intracellular GSH content of the c-Myc low-expressing cells up to the level of controls. Indeed, GSH ethyl ester-mediated increase of GSH abrogated apoptosis induced by cisplatin and melphalan by inhibition of Baxicytochrome c redistribution. The relationship among c-Myc, GSH content, the response to alkylating agent has been also evaluated in the M14 Myc overexpressing clones as well as in the melanoma JR8 c-Myc antisense transfectants. All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis.

  5. Usefulness of tirapazamine as a combined agent in chemoradiation and thermo-chemoradiation therapy at mild temperatures. Reference to the effect on intratumor quiescent cells

    International Nuclear Information System (INIS)

    C3H/He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received one of six different DNA-damaging agents with or without mild temperature hyperthermia (40 deg C, 30 min, MTH). These agents were adriamycin (ADM), mitomycin C (MMC), cyclophosphamide (CPA), bleomycin (BLM), cisplatin (CDDP), and tirapazamine (TPZ). After the drug treatment, the tumor-bearing mice were irradiated with a series of doses of γ-rays. Immediately after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumor cells was determined from the tumors that had not been pretreated with BrdU. MTH significantly increased the MN frequency of total cells in tumors irradiated with γ-rays combined with CPA, BLM, CDDP or TPZ, and that of Q cells in tumors irradiated with γ-rays combined with BLM or TPZ. The sensitivity difference in the MN frequency between total and Q tumor cells was significantly decreased by the combination with TPZ. TPZ combined with radiotherapy and TPZ combined with thermo-radiotherapy at mild temperatures appear to be promising modalities for sensitizing tumor cells in vivo, including Q tumor cells. (author)

  6. Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of microRNAs.

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    Wei-xian Chen

    Full Text Available Adriamycin and docetaxel are two agents commonly used in treatment of breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an RNA-dependent manner. Microarray and polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co-culture assays and miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific miRNAs.

  7. Involved-node radiotherapy combined with deep-inspiration breath-hold technique in patients with Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Purpose. - To assess the clinical outcome of the involved-node radiotherapy (INRT) concept with the use of deep-inspiration breath-hold (DIBH) technique in patients with localized supra-diaphragmatic Hodgkin lymphoma. Patients and methods. - All were patients with stage I-II Hodgkin lymphoma and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy concept according to the European Organization for Research and Treatment of Cancer Guidelines and a spirometer dedicated to DIBH radiotherapy was used for every patient. Results. - Twenty-seven patients with Hodgkin lymphoma (26 patients with primary Hodgkin lymphoma, one with refractory disease), treated from November 2004 to October 2010, were retrospectively analysed. The median age was 27 years (range 16 to 54). Seventeen (63%) patients had stage I-IIA and 10 (37%) had stage I-IIB disease. All patients received two to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine. The median radiation dose to patients was 30,6 Gy (range: 19,8-40). Protection of various organs at risk was satisfactory. Median follow-up, 3-year progression-free and 3-year overall survival were 38 months (range: 7-70), 96% (95% CI: 79-99%) and 95% (95% CI: 75-99%), respectively. Recurrence occurred in one patient (mediastinal in-field relapse). There was one grade 3 acute toxicity (transient pneumonitis). Conclusions. - Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using deep-inspiration breath technique and the involved-node radiotherapy concept. Longer follow-up is needed to assess late toxicity, especially for the heart and the coronary arteries. (authors)

  8. Concurrent radiochemotherapy of locally recurrent or advanced sarcomas of the uterus

    Energy Technology Data Exchange (ETDEWEB)

    Kortmann, B.; Klautke, G.; Fietkau, R. [Dept. of Radiotherapy, Univ. of Rostock (Germany); Reimer, T.; Gerber, B. [Dept. of Gynecology and Obstetrics, Univ. of Rostock, Suedstadt Hospital (Germany)

    2006-06-15

    Background: uterine sarcomas are rare tumors. Until now, no data on the treatment of recurrent or advanced uterine sarcomas using concurrent radiochemotherapy (RCT) has been available. Patients and methods: from 01/1997 to 03/2004, seven patients with locally recurrent (n = 6) or locally advanced uterine sarcomas (n = 1) received concurrent RCT after tumor surgery (R1/2 resection in 3/7 patients). A total radiation dose of 45 Gy was applied in single doses of 1.8 Gy using an external-beam technique; in addition, three to four intracavitary doses of 5 Gy were applied. Concurrent chemotherapy was generally administered as follows: 1.2 g/m{sup 2} ifosfamide on days 1-5 and 29-33 in combination with 50 or 40 mg/m{sup 2} adriamycin on days 2 and 30. 3/7 patients received further cycles of chemotherapy. The median follow-up was 35 months. Results: all recurrences (before RCT) were localized either in the vagina or in or directly proximal to the vaginal stump. The main side effects of RCT were hemotoxicity (grade 3: n = 3/7; grade 4: n = 4/7; neutropenic fever n = 1/7) and diarrhea (grade 3: n = 5/7). At the median follow-up (35 months), 4/7 patients had recurrences (one local recurrence; one lymph node recurrence outside the irradiated field, two distant metastases). Local control in the irradiated field was 80% {+-} 18% after 3 years. Disease-free survival calculated according to Kaplan-Meier was 57% {+-} 19% after 3 years. Presently, 5/7 patients are still alive, corresponding to a 3-year survival rate of 83% {+-} 15%. Conclusion: concurrent RCT shows good local effectiveness with a good long-term survival. Further evaluation in phase II studies is recommended. (orig.)

  9. Wtip- and gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier.

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    Zhijie Xiao

    Full Text Available Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. Especially, the highly specialized cell-cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. This is highlighted by the fact that mutations in molecular components of the slit diaphragm, including nephrin and Cd2-associated protein (Cd2ap, result in proteinuric diseases in man. Dendrin is a poorly characterized cytosolic component of the slit diaphragm in where it interacts with nephrin and Cd2ap. Dendrin is highly specific for the podocyte slit diaphragm, suggesting that it has a dedicated role in the glomerular filtration barrier. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile, and had a normal life span. Morphologically, the glomerulogenesis proceeded normally and adult dendrin-deficient mice showed normal glomerular histology. No significant proteinuria was observed. Following glomerular injury, lack of dendrin did not affect the severity of the damage or the recovery process. Yeast two-hybrid screen and co-immunoprecipitation experiments showed that dendrin binds to Wt1-interacting protein (Wtip and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a. Wtip and Gadd45a mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podocytes. In line with this, we observed the relocation of dendrin to nucleus in adriamycin nephropathy model. Our results indicate that dendrin is dispensable for the function of the normal glomerular filtration barrier and that dendrin interacts with Wtip and Gadd45a.

  10. Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1.

    Science.gov (United States)

    Yi, Ying-Jie; Jia, Xiu-Hong; Wang, Jian-Yong; Li, You-Jie; Wang, Hong; Xie, Shu-Yang

    2016-05-01

    Multidrug resistance (MDR) of leukemia cells is a major obstacle in chemotherapeutic treatment. The high expression and constitutive activation of P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) have been reported to play a vital role in enhancing cell resistance to anticancer drugs in many tumors. The present study aimed to investigate the reversal of MDR by silencing homeobox A10 (HOXA10) in adriamycin (ADR)-resistant human chronic myelogenous leukemia (CML) K562/ADM cells by modulating the expression of P-gp and MRP-1. K562/ADM cells were stably transfected with HOXA10-targeted short hairpin RNA (shRNA). The results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis showed that the mRNA and protein expression of HOXA10 was markedly suppressed following transfection with a shRNA-containing vector. The sensitivity of the K562/ADM cells to ADR was enhanced by the silencing of HOXA10, due to the increased intracellular accumulation of ADR. The accumulation of ADR induced by the silencing of HOXA10 may be due to the downregulation of P-gp and MRP-1. Western blot analysis revealed that downregulating HOXA10 inhibited the protein expression of P-gp and MRP-1. Taken together, these results suggest that knockdown of HOXA10 combats resistance and that HOXA10 is a potential target for resistant human CML. PMID:27035504

  11. Risk factors for development of radiation pneumonitis following radiation therapy with or without chemotherapy for lung cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the risk factors contributing to development of radiation pneumonitis (RP) in patients with lung cancer who undergo radiation therapy to the thorax. Methods and Materials: Development and severity of RP were retrospectively analyzed for 89 patients with lung cancer who underwent radiation therapy with or without chemotherapy at the National Shikoku Cancer Center Hospital between 1991 and 1995. The severity of RP was determined using a modified grading scale based on that of the Radiation Therapy Oncology Group and the European Organization for the Research and Treatment of Cancer. Results: Fifty-two (58%) patients developed RP: 34 patients with Grade 1, 5 with Grade 2, 8 with Grade 3, and 5 with Grade 5 RP. Severe RP tended to develop earlier than less severe RP, but not to a significant extent (p = 0.151). On logistic regression analysis including both patient condition and treatment factors, development of Grade 1 or more severe RP was most frequently observed for Stage I-II disease (p = 0.011). The use of chemotherapy, large daily radiation dose, and once-daily fractionation (vs. twice-daily fractionation) were possibly related to the development of RP (p = 0.057, p = 0.069, and p = 0.092, respectively). For the group of 48 patients who underwent chemo radiation therapy, the use of large daily radiation dose was a significant risk factor for RP (p = 0.014). In addition, the use of once-daily fractionation was a marginally significant risk factor (p = 0.052). Among chemotherapy drugs administered, cisplatin was a favorable factor (p = 0.011), while adriamycin was a risk factor (p = 0.061). Conclusions: In radiation therapy for lung cancer, administration of a large daily dose should be avoided in order to prevent RP, particularly when radiation therapy is combined with chemotherapy

  12. Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

    International Nuclear Information System (INIS)

    Purpose: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. Patients and Methods: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. Results: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. Conclusion: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01)

  13. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

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    Mestre, Francisco [Service of Radiation Therapy, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Gutiérrez, Antonio, E-mail: antoniom.gutierrez@ssib.es [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Rodriguez, Jose [MD Anderson Cancer Center, Madrid (Spain); Ramos, Rafael [Service of Pathology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Garcia, Juan Fernando [Spanish National Cancer Research Centre, Madrid (Spain); Martinez-Serra, Jordi [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Casasus, Marta; Nicolau, Cristina [Service of Radiation Therapy, Policlinica Miramar, Palma de Mallorca (Spain); Bento, Leyre; Herraez, Ines [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain); Lopez-Perezagua, Paloma [Service of Radiology, IDISPA, Palma de Mallorca (Spain); Daumal, Jaime [Service of Nuclear Medicine, IDISPA, Palma de Mallorca (Spain); Besalduch, Joan [Service of Hematology, University Hospital Son Espases, Instituto de Investigación Sanitaria de Palma, Palma de Mallorca (Spain)

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  14. CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity.

    Science.gov (United States)

    Wegner, Binytha; Al-Momany, Abass; Kulak, Stephen C; Kozlowski, Kathy; Obeidat, Marya; Jahroudi, Nadia; Paes, John; Berryman, Mark; Ballermann, Barbara J

    2010-06-01

    The chloride intracellular channel 5A (CLIC5A) protein, one of two isoforms produced by the CLIC5 gene, was isolated originally as part of a cytoskeletal protein complex containing ezrin from placental microvilli. Whether CLIC5A functions as a bona fide ion channel is controversial. We reported previously that a CLIC5 transcript is enriched approximately 800-fold in human renal glomeruli relative to most other tissues. Therefore, this study sought to explore CLIC5 expression and function in glomeruli. RT-PCR and Western blots show that CLIC5A is the predominant CLIC5 isoform expressed in glomeruli. Confocal immunofluorescence and immunogold electron microscopy reveal high levels of CLIC5A protein in glomerular endothelial cells and podocytes. In podocytes, CLIC5A localizes to the apical plasma membrane of foot processes, similar to the known distribution of podocalyxin and ezrin. Ezrin and podocalyxin colocalize with CLIC5A in glomeruli, and podocalyxin coimmunoprecipitates with CLIC5A from glomerular lysates. In glomeruli of jitterbug (jbg/jbg) mice, which lack the CLIC5A protein, ezrin and phospho-ERM levels in podocytes are markedly lower than in wild-type mice. Transmission electron microscopy reveals patchy broadening and effacement of podocyte foot processes as well as vacuolization of glomerular endothelial cells. These ultrastructural changes are associated with microalbuminuria at baseline and increased susceptibility to adriamycin-induced glomerular injury compared with wild-type mice. Together, the data suggest that CLIC5A is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. We postulate that the interaction between podocalyxin and subjacent filamentous actin, which requires ezrin, is compromised in podocytes of CLIC5A-deficient mice, leading to dysfunction under unfavorable genetic or environmental conditions. PMID:20335315

  15. Adjuvant Brachytherapy for Primary and Recurrent Soft-Tissue Sarcoma at WSU

    International Nuclear Information System (INIS)

    The direct application of radiation to the tumor bed following conservative surgery in the treatment of soft-tissue sarcoma may offer excellent local control for patients with primary and recurrent disease. Prognostic factors and outcome parameters were evaluated for fifty-four patients with adjuvant interstitial implants performed since 1983. Thirty-nine patients were treated at initial presentation and 15 for local recurrence. Histology included MFH (n = 19), liposarcoma (n = 17), MPNST (n 4), synovial sarcoma (n = 5), and others (n = 9). There were thirty-nine high grade and 15 low grade tumors. Margins were negative, microscopically positive, and grossly positive in 15, 34, and 7 patients respectively. Thirty-two patients were treated with high dose-rate radiation (HDR) to a median dose of 17.52 Gy. The HDR fraction size ranged from 1.88 to 3.5 Gy (median 2.19 Gy). Nineteen of the HDR patients received additional external-beam radiotherapy (EBRT; 10 to 50 Gy with a median of 39.6 Gy). Twenty-two patients were treated with low dose-rate (LDR) implants (median dose 25 Gy). Eighteen of the LDR patients received EBRT (median dose 30Gy). With a median follow-up time of 50 months, actuarial 4-year local control, overall survival, and disease-free survival were 82%, 59%, and 58%, respectively. Mild to moderate skin and wound complications (48%) were treated conservatively. In three cases further surgery was required to manage wound toxicity. One patient death was attributed to adriamycin cardiotoxicity. All local failures occurred within 32 months. Histologic grade and implant type were not predictive of local control. In addition, the local control and survival of patients treated for primary versus recurrent disease was not different

  16. Testicular Synovial Sarcoma: A Case Report

    International Nuclear Information System (INIS)

    This paper reports a case of testicular synovial sarcoma with molecular genetic analysis. A 24-year-old male presented with painless scrotal mass. Ultrasonography showed a heterogeneous mass of 66 mm × 34 mm in size involving the inguinal region. Histological examination of a surgical biopsy showed a grade III monophasic growth pattern of spindle cell proliferation. Immunohistochemical analyses indicated positive staining for pancytokeratine and epithelial membrane antigen. Cytogenetic analysis showed the presence of CYT-SSX1 mutation, and CT scan showed non-specific pleural micro-nodules with a size of 7.5 mm. The patient had an extended left orchidectomy but was lost to follow-up for 1 year. A local recurrent scrotal mass of 32 mm × 25 mm, multiple inguinal lymph nodes, and increased pleural nodules, which were confirmed by histological examination, were treated with three cycles of adriamycine and ifosfamide chemotherapy, surgical resection, and radiotherapy with complete response. After 3 months, the patient developed local recurrence and pulmonary metastases that did not respond to second-line chemotherapy based on gemcitabine and paclitaxel. The patient had dyspnea at the time of this writing and chest pain, and is under third-line chemotherapy based on Deticene after 30 months of following up. This patient died on November 16, 2012 after a resperatory failure and malignant pelural effusion. Synovial sarcoma should be considered in the differential diagnosis of soft tissue tumor and it should be aggressively treated to improve prognosis. Although our patient has shown numerous factors of bad prognosis, he has had a relatively long survival time

  17. Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma.

    Science.gov (United States)

    Zhao, Ziyi; Chen, Changjin; Lin, Junzhi; Zeng, Wentong; Zhao, Juan; Liang, Yindan; Tan, Qinrui; Yang, Chao; Li, Hui

    2016-09-01

    The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC), and therefore these tumors are highly resistant to chemotherapeutic agents, including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53 (TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is frequently functional, yet the tumors remain highly insensitive to chemotherapy. This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC. The present study aimed to detect the chemosensitivity of CCRCC. The expression of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm that VHL and P53 are both required for chemosensitivity, VHL and P53 were co‑expressed in 786‑O cells. The results of the functional antagonist assay (which assessed the IC50 values, i.e. the half maximal inhibitory concentration) confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle arrest was measured by propidium iodide staining following treatment with ADM or sunitinib. Further analysis indicated that co‑expression of VHL and P53 inhibited cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase, and promoted apoptosis following treatment with ADM or sunitinib. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the regulatory role of VHL is dependant on the activation P53. PMID:27485825

  18. Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu; Du, Feiya; Chen, Wei; Yao, Minya; Lv, Kezhen; Fu, Peifen, E-mail: fupeifendoczju@163.com

    2013-12-10

    Background: Breast cancer is the major cause of cancer-related deaths in females world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due to drug resistance, which has been shown to be associated with the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT and drug resistance in breast cancer cells remain unclear. Dual specificity phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is associated with cellular proliferation and differentiation; however, its role in breast cancer progression is controversial. Methods: We used cell viability assays, Western blotting and immunofluorescent staining, combined with siRNA interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cells, and investigate the underlying mechanisms. Results: Knockdown of DUSP4 significantly increased the chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype. Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as demonstrated by upregulation of epithelial biomarkers and downregulation of mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR cells to doxorubicin. Conclusions: DUSP4 might represent a potential drug target for inhibiting drug resistance and regulating the process of the EMT during the treatment of breast cancer. - Highlights: • We used different technologies to prove our conclusion. • DUSP4 knockdown increased doxorubicin chemosensitivity in breast cancer cells. • DUSP4 is a potential target for combating drug resistance in breast cancer. • DUSP4 is a potential target for regulating the EMT in breast cancer.

  19. The role of mitoxantrone in non-Hodgkin's lymphoma.

    Science.gov (United States)

    Armitage, James O

    2002-04-01

    The development of doxorubicin was an important advance in the treatment of patients with non-Hodgkin's lymphoma (NHL). Alternatives to doxorubicin, such as mitoxantrone (Novantrone), have less nonhematologic toxicity and could offer a therapeutic advantage in some situations if similar antilymphoma activity exists. Several combination regimens that include mitoxantrone have been shown to be active. These include mitoxantrone/ifosfamide (Ifex) and mitoxantrone/etoposide combinations as salvage therapy for aggressive lymphomas. Mitoxantrone in combination with fludarabine (Fludara) for the treatment of newly diagnosed follicular lymphomas and in combination with fludarabine and dexamethasone for relapsed/refractory follicular lymphomas has produced high complete response rates. Other evolving uses of mitoxantrone include combination therapy with cladribine (Leustatin) or rituximab (Rituxan), and as part of conditioning regimens for hematopoietic stem cell transplantation. In diffuse aggressive lymphoma, mitoxantrone, 10 mg/m2, substituted for doxorubicin, 50 mg/m2, results in a poorer response when CNOP (cyclophosphamide [Cytoxan, Neosar], mitoxantrone [Novantrone], vincristine [Oncovin], prednisone) is compared to CHOP (cyclophosphamide, doxorubicin HCl vincristine, prednsione); however, increasing the mitoxantrone dose to 12 mg/m2 in either the CNOP or CMP-BOP (cyclophosphamide, mitoxantrone, procarbazine [Matulane], bleomycin [Blenoxane], vincristine, prednisone) regimens yields results comparable to those achieved with the doxorubicin-containing regimen. Comparable results have also been observed when 10 mg/M2 of mitoxantrone was substituted for 45 mg/M2 of doxorubicin in the m-BACOD (methorexate, bleomycin, doxorubicin [Adriamycin], cyclophosphamide, vincristine, dexamethasone) regimen. Mitoxantrone is active in NHL, and combinations including mitoxantrone can be used effectively and may provide an advantage in the elderly. PMID:12017536

  20. Comparative proteomic analysis of differentially expressed proteins between K562 and K562/ADM cells

    Institute of Scientific and Technical Information of China (English)

    SHEN Shao-hua; GU Long-jun; LIU Pei-qing; YE Xin; CHANG Wei-shan; LI Ben-shang

    2008-01-01

    Background Multidrug resistance to chemotherapeutic agents is an important clinical problem during the treatment of leukemia.The resistance process is multifactorial.To realize the totaI factors involved in multidrug resistance,we analyzed the differentially expressed proteins of K562 and K562/ADM cells and we investigated one of the up-regulated proteins(CRKL)using siRNA to determine its role in K562/ADM cells.Methods Altered protein expressions between K562/S(K562 ADM-sensitive cell line)and K562/ADM(K562 multidrug resistant cell line induced by adriamycin)were identified by 2D-DIGE coupled with mass spectrometry. Meanwhile,we confirmed the differential expression of CRKL and Stathmin in both K562 and K562/ADM cells by Western blot analysis.Furthermore,we used RNA interference to silence the CRKL gene expression.Results Among the 9 differentially expressed proteins,3 were up-regulated in K562/ADM cells,while 6 were down-regulated in the K562/ADM cells compared with its parent cell line.The expression of CRKL was up-regulated significantly in K562/ADM cells,and it can be decreased by recombinant lentivirus.Moreover,the multidrug resistance of K562/ADM cells was efficiently reversed by silence of CRKL gene expression.Conclusions The data provided the differentially expressed proteins jn K562 and jts resistant cell line and highlights the power of 2D-DIGE for the discovery of resistance markers in cancer.We found CRKL may be a new protein involved in the multidrug resistanse of leukaemia cells.

  1. Prediction of P-glycoprotein expression and chemoresistant character of gliomas by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Toshihiko; Togawa, Takashi; Oga, Masaru; Osato, Katsunobu [Chiba Cancer Center (Japan); Namba, Hiroki; Fujimoto, Shuichi

    2000-09-01

    In this prospective study of 25 malignant gliomas, we correlated the {sup 99m}Tc-MIBI uptake/{sup 201}Tl uptake ratio (MIBI/Tl) with the expression of P-glycoprotein in tumor tissue and the tumor's response to anticancer agents. All patients underwent {sup 99m}Tc-MIBI and {sup 201}Tl SPECT before surgery. Semiquantitative assessment of tracer uptake was performed using the ratio of radioactivity in the tumor relative to normal scalp. Immunohistochemical studies were performed on paraffin sections using an anti-P-glycoprotein monoclonal antibody, JSB-1. Chemosensitivity of the gliomas to following 12 anticancer agents: vincristine, vinblastine, vindesine, etoposide, irinotecan, daunomycin, adriamycin, aclarubicin, epirubicin, pirarubicin, actinomycin and mitoxantrone, was determined by an in vitro assay using surgical specimens, and chemosensitivity was expressed as the number of effective drugs. Gliomas expressing P-glycoprotein were significantly less chemosensitive than gliomas without the glycoprotein (p=0.010), and MIBI/Tl of gliomas expressing P-glycoprotein was significantly smaller than tumors without expression (p=0.008). From the prognostic point of view, gliomas showing MIBI/Tl of 0.6 or less had fewer effective drugs (p=0.008). However, MIBI/Tl was not effective at predicting overall survival in patients with malignant glioma. From these results, we concluded that efflux of {sup 99m}Tc-MIBI through P-glycoprotein could be evaluated by MIBI/Tl, and this index reflected well the chemoresistant character of malignant gliomas. (author)

  2. Effect of multidrug resistance gene-1(mdr1) overexpression on in-vitro uptake of {sup 99m}Tc-sestaMIBI in murine L1210 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Kyung Ah; Lee, Jae Tae; Lee, Sang Woo; Kang, Do Young; Sohn, Snag Kyun; Lee, Jong Kee; Jun, Soo Han; Lee, Kyu Bo [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of); Chung, June Key [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    1999-02-01

    To determine whether {sup 99m}Tc-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively {sup 99m}Tc-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular {sup 99m}Tc-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr 1 gene) overexpression. We measured percentage uptake of {sup 99m}Tc-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of {sup 99m}Tc-MIBI were also evaluated with or without overexpression of mdr1 gene in cultured murine leukemia L1210 cells. The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of {sup 99m}Tc-MIBI was higher in mdr1 negative L1210 cells than those of mdr1 positive cells, and higher when incubated in 37 .deg. C than 4 .deg. C. In the presence of verapamil, cyclosporin or dipyridamole, {sup 99m}Tc-MIBI uptake was increased upto 604% in mdr1 positive cells. Cellular uptake of {sup 99m}Tc-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest the {sup 99m}Tc-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro.

  3. Bladder Preservation by Combined Modality Therapy for Invasive Bladder Cancer: A Five-Year Follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Ho; Lim, Ji Hoon; Seong, Jin Sil; Pyo, Hong Ryull; Koom, Woong Soup; Suh, Chang Ok; Hong, Sung Jun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materials : From 1991 Jan, through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated width induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of al patients was 70 months. Results : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was 67.3%. Complete remission rate was 80% (20/25). Sixth-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a 67.3% overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages. Sixty-three percent of long term survivors preserved their bladders.

  4. Skeletal muscle metastasis from transitional cell carcinoma of the urinary bladder: Clinicoradiological features

    Energy Technology Data Exchange (ETDEWEB)

    Nabi, G. E-mail: nabeegholam@hotmail.com; Gupta, N.P.; Gandhi, D

    2003-11-01

    AIM: To define the clinicoradiological characteristics of skeletal muscle metastasis from transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: A retrospective review of all patients with skeletal muscle metastasis was undertaken between January 1999 to December 2001. Patients suspected of having a metastasis on radiological examinations, and subsequently proven to have metastatic disease on histological examination were included in study. The clinical presentation and radiological features of five patients with skeletal muscle metastasis from bladder tumours were reviewed from hospital records. RESULTS: Twenty-four patients had skeletal muscle metastasis from various primaries. Of these five patients had previous or concurrent primary tumours in the bladder. Patients were aged between 27-70 years (mean 52 years), and all had persistent, localized pain with or without accompanying swelling. The muscles involved were psoas in three patients, adductor muscles of thigh in one and rectus abdominis in one. Four patients had radical cystectomy with urinary diversion (two ileal conduit and two orthotopic sigmoid neobladder). One patient presented with bladder tumour and concomitant muscular metastasis. All patients underwent helical computed tomography (CT) before confirmation of diagnosis by fine-needle aspiration (FNA) or biopsy. The typical appearance of low-density enhancing lesions on CT was mistaken for abscess in two patients and failure to respond to conservative treatment led to suspicion of metastasis. Diagnosis was proven histologically in all patients (FNA in three and biopsy in two). All patients had palliative chemotherapy (Mitomycin, Vincristine, Adriamycin and Cyclophosphamide). Two patients had local palliative 3500 rad radiotherapy for persistent pain. Mean survival was 8 months (range 6-12 months). CONCLUSION: Muscular metastasis from urothelial tumours typically presents with persistent localized pain with or without swelling. The

  5. Lymphomas in children

    International Nuclear Information System (INIS)

    At St. Jude's Research Hospital, all patients with stage III and stage IV disease received induction with vincristine, cyclophosphamide, prednisone, and Adriamycin with randomization to involved-field radiation therapy (3000-3500 cGY, except whole-abdomen 2000-2500 cGY plus boost), with all cases subsequently being randomized for CNS prophylaxis and maintenance with oral 6-mercaptopurine and methotrexate. In 46 randomized patients, there was no significant difference in complete remission or of disease-free survival between the two treatment arms. There was more mucositis, esophagitis, and enteritis in the irradiated patients. Patients with stages II through IV disease were also randomized to receive CNS prophylaxis or not (2400 cGY in 12 fractions to the cranium with 5 doses of intrathecal methotrexate); 4 of 16 receiving no prophylaxis relapsed first in the CNS, as opposed to 1 of 18 who received prophylaxis. However, there was no difference in survival. The CCSG has recently reported results of a randomized trial comparing a regimen of four dogs (cyclophosphamide, vincristine, methotrexate, and prednisone) with a modified LSA2-L2 regimen. All patients in both arms received maintenance intrathecal methotrexate; most received radiation to bulk disease. Results indicated that although patients with lymphoblastic mediastinal presentations may do better with the LSA2-L2 modification, those with diffuse undifferentiated histology appear to fare better with the four-drug regimen. The overall 3-year relapse-free survival was 84%. However, a nonrandomized Pediatric Oncology Group Study with central pathology review reported more encouraging results for the nonlymphoblastic non-Burkitt's histologies with a modified LSA2-L2 regimen. A current Pediatric Oncology Group randomized protocol will assess the contribution of radiation therapy in stages I and II disease

  6. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    International Nuclear Information System (INIS)

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

  7. Encapsulating magnetic and fluorescent mesoporous silica into thermosensitive chitosan microspheres for cell imaging and controlled drug release in vitro.

    Science.gov (United States)

    Gui, Rijun; Wang, Yanfeng; Sun, Jie

    2014-01-01

    In this study, for the first time, multifunctional inorganic/organic core/shell hybrid microspheres consisted of Fe3O4 nanoparticles/CdTe quantum dots dual-embedded mesoporous silica nanocomposites (MQ-MSN) as cores and P(N-isopropylacrylamide)-graft-Chitosan microgels (PNIPAM-g-CS) as shells were prepared by copolymerization of NIPAM and CS in the presence of MQ-MSN. The preparation of microspheres (i.e., MQ-MSN/PNIPAM-g-CS) included three stages. First, Fe3O4/CdTe nanocomposites (MQ NCs) were prepared by self-assembly of electrostatic adsorption. Second, MQ NCs were encapsulated into silica spheres by modified Stöber method to obtain MQ-MSN. Third, NIPAM monomers were initiated to fabricate PNIPAM networks with MQ-MSN distributed below the lower critical solution temperature (LCST) of PNIPAM, and then PNIPAM reacted with CS to form PNIPAM-g-CS copolymers above the LCST, meanwhile the PNIPAM networks collapsed to form microspheres, resulting in the MQ-MSN encapsulated into microspheres. The microspheres were systematically characterized, displaying perfect magnetic/fluorescent properties and thermo-sensitivity. HepG2 cancer cells treated with the microspheres revealed bright fluorescence imaging. Both the efficiency and capacity of Adriamycin (ADM) loaded into the microspheres were gradually increased with ADM concentration increasing. The ADM cumulative release in vitro from ADM-loaded microspheres was significant at a higher temperature (or a lower pH). The released ADM still maintained high anticancer activity, and the blank microsphere carriers hardly produced toxicity to HepG2 cells. Hence, the multifunctional microspheres exhibited a promising application especially as thermo/pH-sensitive drug carriers for in vivo therapy. PMID:24060924

  8. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

    Directory of Open Access Journals (Sweden)

    Zhong Xingguo

    2010-08-01

    Full Text Available Abstract Background To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Methods Established human hepatocellular carcinoma adriamycin (ADM multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium method was used to detect drug resistance of the three different sub-lines of cells. Results The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum, but showed a significant difference in resistance to Bel-7402 IC50 value (P V, 46 h (Bel-7402/ADML, and 45 h (Bel-7402/ADMS. The excretion rates of ADM were significantly increased compared with the parent cell (34.14% line and were 81.06% (Bel-7402/ADMV, 66.56% (Bel-7402/ADML and 61.56% (Bel-7402/ADMS. Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P P > 0.05. Conclusions Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs.

  9. Primary spinal epidural extraosseous Ewing's sarcoma: Report of five cases and literature review

    International Nuclear Information System (INIS)

    Ewing's sarcoma is the most common malignant bone tumour occurring in children and adolescents and exists in two different clinico pathological entities: osseous Ewing's sarcoma (OES) and extraosseous Ewing's sarcoma (EES). Five cases of primary epidural EES are described, which presented with non-specific symptoms leading to a long diagnostic delay. The median age at diagnosis was 22 years (range 13-36 years). The median diagnostic delay was 3 months. All patients had one or more neurological deficits. All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46-50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles. The mean follow-up period is 21.2 months (range 11-32 months). Four of the five patients achieved a complete remission and are disease free at the time of writing this report. Two patients have a residual neurological deficit - both having presented with long history of neurological deficit. Primary spinal epidural EES should be suspected whenever young patients present with back pain and/or radicular pain, have abnormal neurology and an extradural mass is demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy) and combination chemotherapy (VAC alternating with ICE) achieved local and systemic control in these patients. A greater number of patients and longer follow up are required to evolve a generally accepted treatment policy for this aggressive but potentially curable malignancy. Copyright (2001) Blackwell Science Pty Ltd

  10. Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer

    International Nuclear Information System (INIS)

    Drug resistance in breast cancer is a major obstacle to successful chemotherapy. In this study we used cDNA microarray technology to examine gene expression profiles obtained from fine needle aspiration (FNA) of primary breast tumors before and after systemic chemotherapy. Our goal was to determine the feasibility of obtaining representative expression array profiles from limited amounts of tissue and to identify those expression profiles that correlate with treatment response. Repeat presurgical FNA samples were taken from six patients who were to undergo primary surgical treatment. Additionally, a group of 10 patients who were to receive neoadjuvant chemotherapy underwent two FNAs before chemotherapy (adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2) followed by another FNA on day 21 after the first cycle. Total RNA was amplified with T7 Eberwine's procedure and labeled cDNA was hybridized onto a 7600-feature glass cDNA microarray. We identified candidate gene expression profiles that might distinguish tumors with complete response to chemotherapy from tumors that do not respond, and found that the number of genes that change after one cycle of chemotherapy was 10 times greater in the responding group than in the non-responding group. This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings also demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies

  11. ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERY FOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

    Institute of Scientific and Technical Information of China (English)

    XU Guang-chuan; RONG Tie-hua; LIN Peng

    1999-01-01

    Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage Ⅰ-Ⅲ) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX)300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 d1,cisplatin (DDP) 20 mg/m2, d1-5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600-900 mg/d for 1year (adjuvant chemotherapy group). The other 35patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4%in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage Ⅲwas 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage Ⅰ-Ⅱ in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage Ⅲ, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

  12. Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy

    International Nuclear Information System (INIS)

    Doxorubicin (Adriamycin®) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is restricted by a cumulative and progressive cardiomyopathy that develops with repeated dosing. Fundamental to the cardiac failure is an interference with mitochondrial respiration and inhibition of oxidative phosphorylation. Global gene expression arrays in cardiac tissue indicate that inhibition of mitochondrial oxidative phosphorylation by doxorubicin (DOX) is accompanied by a decreased expression of genes related to aerobic fatty acid oxidation and a corresponding increase in expression of genes involved in anaerobic glycolysis, possibly as an alternate source for ATP production. The aim of this investigation was to determine whether this is also manifest at the metabonomic level as a switch in metabolic flux in cardiac tissue, and whether this can be averted by co-administering the cardioprotective drug, dexrazoxane (DZR). 13C-isotopomer analysis of isolated perfused hearts from male Sprague-Dawley rats receiving 6 weekly s.c. injections of 2 mg/kg DOX demonstrated a shift from the preferential oxidation of fatty acids to enhanced oxidation of glucose and lactate plus pyruvate, indicative of a compensatory shift towards increased pyruvate dehydrogenase activity. Substrate-selective isotopomer analysis combined with western blots indicate an inhibition of long-chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine transport. Co-administering DZR averted many treatment-related changes in cardiac substrate metabolism, consistent with DZR being an effective cardioprotective agent against DOX-induced cardiomyopathy. This switch in substrate metabolism resembles that described for other models of cardiac failure; accordingly, this change in metabolic flux may represent a general compensatory response of cardiac tissue to imbalances in bioenergetic demand and supply, and not a characteristic unique to DOX-induced cardiac failure itself.

  13. Adenoma clear cell carcinoma of prostatic utricle. Report of a case. Literature Review

    International Nuclear Information System (INIS)

    The prostatic utricle (UP) is a rudimentary structure derived from the Müllerian ducts (paramesonephric), which gives rise to the female genital tract in its portion flow and Wollfianos products (mesonephric), which causes the male seminal tubes urogenital sinus and in the caudal segment. It is located in the central portion of the prostatic urethra. UP pathology is rare in the literature and only few isolated cases have been reported and rare reviews. UP neoplasms are extremely rare. The first report on the literature is the year 1967 in a man 66 years in which the diagnosis was incidental in a piece of prostatectomy. Objective: The aim of this paper is to review the literature on this rare condition from the report of a clinical case. Case report: Male patient, 15 years who presented with hematuria. the tomography showed right renal agenesis, hypertrophic left kidney and a solid mass retrovesical in prostate topography. The transrectal ultrasound guided biopsy remains informed embryonic kidney blastoma and immunohistochemical profile is specific to urothelial epithelium and glomerular (BPM CK7 strongly positive). It is involved, resecting the tumor whose pelvic pathology (AP) corresponded to clear cell adenocarcinoma UP. Pursuing a post-operative complications and remains without clinical tomographic control locoregional relapse was diagnosed 5 months after. Get chemotherapy type adriamycin-cisplatin with complete clinical response after the 2nd cycle of treatment and rapid lesion progression at the end of the 6th cycle. Was re hospitalized resecting one laterovesical mass right, leaving in situ a left laterovesical similar mass. the AP was similar to the original. Currently, the patient underwent a left nephrostomy is planned initiation of palliative chemotherapy of weekly Docetaxel type. Conclusions: Given the rarity of the disease, and little literature there is no data on evolution and sensitivity to treatment. In the case of this patient highlight the high

  14. RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    GUAN Hong-geng; XUE Wan-jiang; QIAN Hai-xin; ZHOU Xiao-jun; QIN Lei; LAN Jing

    2009-01-01

    Background The antitumor role of Ras association domain family 1A (RASSFIA) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSFIA in hepatoceliular carcinoma, and study the mechanisms of cell apoptosis induced by RASSFIA.Methods After stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Westem blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.Results Wild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatJn treatment.Conclusion Wild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

  15. Renoprotective effect of the antioxidant curcumin: Recent findings

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    Joyce Trujillo

    2013-01-01

    Full Text Available For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2, inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.

  16. Experimental chemo- and radio-therapy on human cholangiocarcinoma transplanted to nude mice

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    Kubota, T.; Hanatani, Y.; Yamada, Y.; Tsuyuki, K.; Nakada, M. (Keio Univ., Tokyo (Japan). School of Medicine)

    1981-06-01

    A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and combination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, /sup 3/H-thymidine uptake labeling index (L.I.), and mitotic (M.I.) on 24 and 48 hrs. after MMC (0.5 mg/kg) and radiation (500 rads/mouse). By MMC and radiation, 4 n cells increased with the decrease of 2 n cells. And this change was remarkable in radiation than MMC. L.I. was depressed almost 10% on 24 hrs. after MMC and radiation. Although M.I. was depressed slightly by MMC, it was stable after radiation. From these findings the recruitment of cells from G/sub 1/ to G/sub 2/M and the G/sub 2/ block by MMC and radiation was suggested. As these changes were more remarkable by radiation, the combination chemoradiotherapy was thought to be more effective when the radiation was performed before MMC administration.

  17. Experimental chemo- and radio-therapy on human cholangiocarcinoma transplanted to nude mice

    International Nuclear Information System (INIS)

    A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and conbination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, 3H-thymidine uptake labeling index (L.I.), and mitotic (M.I.) on 24 and 48 hrs. after MMC (0.5 mg/kg) and radiation (500 rads/mouse). By MMC and radiation, 4 n cells increased with the decrease of 2 n cells. And this change was remarkable in radiation than MMC. L.I. was depressed almost 10% on 24 hrs. after MMC and radiation. Although M.I. was depressed slightly by MMC, it was stable after radiation. From these findings the recruitment of cells from G1 to G2M and the G2 block by MMC and radiation was suggested. As these changes were more remarkable by radiation, the combination chemoradiotherapy was thought to be more effective when the radiation was performed before MMC administration. (author)

  18. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    International Nuclear Information System (INIS)

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation

  19. Sentinel lymph node biopsy using dye alone method is reliable and accurate even after neo-adjuvant chemotherapy in locally advanced breast cancer - a prospective study

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    Mishra Ashwani

    2011-02-01

    Full Text Available Abstract Background Sentinel lymph node biopsy (SLNB is now considered a standard of care in early breast cancers with N0 axillae; however, its role in locally advanced breast cancer (LABC after neo-adjuvant chemotherapy (NACT is still being debated. The present study assessed the feasibility, efficacy and accuracy of sentinel lymph node biopsy (SLNB using "dye alone" (methylene blue method in patients with LABC following NACT. Materials and methods Thirty, biopsy proven cases of LABC that had received three cycles of neo-adjuvant chemotherapy (cyclophosphamide, adriamycin, 5-fluorouracil were subjected to SLNB (using methylene blue dye followed by complete axillary lymph node dissection (levels I-III. The sentinel node(s was/were and the axilla were individually assessed histologically. The SLN accuracy parameters were calculated employing standard definitions. The SLN identification rate in the present study was 100%. The sensitivity of SLNB was 86.6% while the accuracy was 93.3%, which were comparable with other studies done using dual lymphatic mapping method. The SLN was found at level I in all cases and no untoward reaction to methylene blue dye was observed. Conclusions This study confirms that SLNB using methylene blue dye as a sole mapping agent is reasonably safe and almost as accurate as dual agent mapping method. It is likely that in the near future, SLNB may become the standard of care and provide a less morbid alternative to routine axillary lymph node dissection even in patients with LABC that have received NACT.

  20. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

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    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2+ patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2− patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2+ and COX-2− patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT

  1. In vitro studies to evaluate the antioxidant property of salidroside and rosavin and protective effects of electron beam radiation induced damages in human dermal fibroblasts

    International Nuclear Information System (INIS)

    Rosavin and Salidroside are active component of Rhodiola rosea, it is a phenylpropanoid derivative of plant. Rhodiola rosea, also known as 'golden root' or 'roseroot' belongs to the plant family Crassulaceae. Rhodiola grows primarily in dry sandy ground at high altitudes in the arctic areas of Europe and Asia. Plant is rich with phenolic compounds, known to have a strong antioxidant property. Studies have shown that Rhodiola rosea has a capacity to decrease toxicity of Adriamycin (anti-cancer drugs), while it enhances their anti-carcinogenic effects. Enhanced antioxidant activity of Rhodiola rosea play role in the prevention of both chronic disease and aging. Present study is aimed to determine the antioxidant property of Rosavin and Salidroside and dose determination on human dermal fibroblast against dermal fibroblast. Rosavin and Salidroside were dissolved in 10% DMSO. Invitro biochemical assays like DPPH radical scavenging assay, Ferric Anion Reducing Potential using TPTZ, Nitric Oxide scavenging assay, Total antioxidant determination assay, Super Anion Radical Scavenging assays were carried out to know property of the extract. Extracts were then treated on monolayer dermal fibroblast cells survival assay was performed. Salidroside has shown 80% total antioxidant property compare to Rosavin with respect Ascorbic acid as a standard. 100'R concentration of Salidroside and Rosavin has quite equal potential to scavenging DPPH similar like Ascorbic acid. Ferric Anion Reducing Potential using TPTZ, Nitric Oxide scavenging assays have also shown both Salidroside and Rosavin has a good antioxidant property. Invitro studies on dermal fibroblast have shown remarkable protective effect on normal and irradiated groups. (author)

  2. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

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    Iwasawa, Toshihisa; Matsumoto, Hidetsugu [Social Health Insurance Medical Center, Tokyo (Japan)

    1996-11-01

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier`s method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier`s method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  3. Patterns of relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy followed by surgery and radiotherapy

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    Yadav B

    2007-01-01

    Full Text Available Aims : To define the clinical and pathological predictors of locoregional recurrence (LRR in locally advanced breast cancer (LABC patients treated with neoadjuvant chemotherapy (NACT. Materials and Methods : We retrospectively reviewed the outcome of 141 patients with stage II to stage III carcinoma breast treated at Department of Radiotherapy, PGIMER, Chandigarh from 1998-2002. Mean age of the patients was 46 years, 49% of patients were premenopausal and 51% were postmenopausal. The tumor stage was T2 in 18%; T3 in 61% and T4 in 26% of the patients. NACT regimen given was FAC (5-fluorouracil, adriamycin and cyclophosphamide in 85% and CMF (cyclophosphamide, methotrexate and 5-Fu in 15% patients. Results : After NACT, surgery was possible in 95% patients. Conservative surgery was possible in 23% patients and mastectomy was done in 72% of patients. Pathological complete response (pCR was seen in 18% patients and pathological partial response (pPR in 69% of patients. Stable and progressive disease was seen in 6% and 7% of patients respectively. Adjuvant radiation therapy was given to 86% patients. Six percent patients developed progressive disease and 4% of patients did not turn up for radiation. Five year LRR was 6% and relapse free survival (RFS was 94%. Thirty-two (23% patients developed distant metastasis resulting in distant metastasis free survival of 77%. The factors that correlated positively with LRR on univariate analysis included tumor stage, stage and pathological nodal stage. However, on multivariate analysis, tumor stage and pathological nodal stage were significant. Factors that correlated for distant relapse were tumor stage, response to chemotherapy, type of surgery, extracapsular extension (ECE and tamoxifen therapy. On multivariate analysis only ECE was the significant factor that correlated with distant relapse free survival. Conclusion : Thus, tumor stage and pathological nodal stage remains the most important predictor of LRR

  4. Biochemical and histopathological studies on the protective effect of propionyl-L-carnitine against cardiotoxicity in rats

    International Nuclear Information System (INIS)

    In many kinds of thoracic cancers, the radiation dose that can safely be delivered to the target volume is limited by the tolerance dose of the surrounding tissue. it has been hypothesized that irradiation of whole body may be an additional risk factor for the development of early radiation -induced cardiotoxicity. Adriamycin (ADR)is a widely used anthacycline anticancer agent. the development of cumulative dose-related cardiotoxicity forms the major limitation of clinical ADR use combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy . However, the combination of ADR and irradiation (IRR) could precipitate the unexpected expression of congestive heart failure. oxidative lesions induced by IRR and ADR could represent one of the pathogenic factors of myocardial dysfunction . The aim of this study is to investigate whether changes in the plasma levels of plasma endothelin-1 (ET-1) total nitrate/nitrite NO (x) have a relationship with the development of ADR and or IRR -induced cardiotoxicity. Also, propionyl-l-carnitine (PLC), a natural short chain derivative of l-carntine, has been evaluated in this study as a potential protective agent against adr and/or IRR-indused cardiotoxicity using biochemical and histopathological approaches. This data obtained revealed that , whole body irradiation and ADR induced a statistically significant increase in plasma ET-1, NO(x) and NO(x) in cardiac tissues. combination of IRR and ADR induced significant increase in ET-1 and NO(x) compared to each group alone . Preadminstration of plc showed protective effect against the increase in ET-1 and NO (x) . Light microscopic exmination revealed myocardial degenerative changes, which were more frequently encounted as the duration of ADR administration was increased. also whole body γ -irradiation 2 gy induced myocardial capillary damage, interstitial oedema between muscle fibers, myolsis or necrosis and inflammatory cells

  5. Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma

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    One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis-platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred

  6. Bendamustine in the treatment of non-Hodgkin’s lymphomas

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    Fredrick Hagemeister

    2009-12-01

    Full Text Available Fredrick Hagemeister1, George Manoukian21Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center Houston, TX, USA; 2Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USAPurpose: To review available data using bendamustine alone and in combination with other chemotherapeutic agents in treatment of patients with non-Hodgkin’s lymphomas.Methods: Internet database searches and literature review.Results: Bendamustine was approved in March 2008 by the United States Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia. Many trials have been performed over the last decade using bendamustine not only as monotherapy, but also in combination with other agents including rituximab, vincristine, mitoxantrone, fludarabine, and other agents as therapy for patients with relapsed non-Hodgkin’s lymphomas, and recently was approved for use in therapy of patients with relapsed indolent lymphomas considered refractory to rituximab therapy. As monotherapy, bendamustine induces good responses with only minor side effects. In combination with other agents, efficacy improves, especially when given in combination with rituximab. The drug has also been studied in combination with rituximab as initial therapy for indolent lymphomas, and has excellent activity with less toxicity than R-CHOP (rituximab – cyclophosphamide, hydroxydaunorubicin [Adriamycin], Oncovin [vincristine], and prednisone/prednisolone.Conclusion: Overall, bendamustine has demonstrated promising results as therapy for non-Hodgkin’s lymphomas and should be included in the armamentarium of agents used to treat relapsed indolent non-Hodgkin’s lymphomas and may prove valuable as initial therapy for these diseases. Further studies are being conducted to demonstrate the efficacy of this drug in combination with other agents.Keywords: bendamustine, non-Hodgkin’s lymphomas, relapsed lymphoma

  7. Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature

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    Yang Qing-Xu

    2012-01-01

    Full Text Available Abstract Only a few cases of extranodal Epstein-Barr virus (EBV-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone, but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1197421158639299

  8. Uses of chemotherapy together with radiation, and its biological basis

    International Nuclear Information System (INIS)

    Effect of use of anticancer drugs together with radiation, especially effects of Actinomycin D (AMD), Bleomycin (BLM), and Adriamycin (Ad) which seemed to have synergistic effect, and other substances which have possibility to have synergistic effect were described. It was clarified that AMD out of them showed synergistic effect to inhibit repair of sublethel damage induced by irradiation in addition to anticancer effect itself. Therefore, it is thought that use of AMD is effective especially to cancer with high radioresistance and it is better to administer this drug just before or just after irradiation. It seems to be better to administer at one time with high concentration in the allowable range. It is difficult to come to a conclusion as to BLM and Ad, generalized as well as the conclusion of AMD, but it seems to be better to use BLM and Ad together with irradiation at the same time. As BLM is highly effective especially to epithelial cells, it must be necessary to investigate whether there is a difference of characteristics between cells. In any case, there are two great factors, the concentration and action time (containing the time remaining in vivo) of drugs, and moreover, another factor, time relation to irradiation is added. Therefore, an experiment schedule is complicated so much, and it is important to study quantitatively on the basis of systematic experimental plan. As to clinical application of them, it is necessary to perform an experiment in vitro which is exullent in estimation and an experiment in vivo which certified the effects in keeping organic cooperation. (Tsunoda, M.)

  9. Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy

    International Nuclear Information System (INIS)

    The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972-1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion

  10. Treatment of osteosarcoma

    International Nuclear Information System (INIS)

    During 1970-86, 97 patients with higly malignant osteosarcoma, localized to an ectremity without evident metastases, were treated at the Norwegian Radium Hospital. The treatment protocol was changed twice during this period. From 1970 to 1975, 25 patients were given primary irradiation with high doses followed by amputation after 3-4 months if distant metastases were not present. Amputations were carried out as planned in eleven cases. Two patients who later developed solitary lung metastases were treated by resection and both are alive. The overall long-term survival was 24%. From 1975 to 1980, 40 patients were treated with primary amputation followed by adjuvant chemotherapy for one year. Three different combinations were given alternatively with two and three weeks interval. The main drugs were adriamycin, cyclophosphamide and methotrexate (2 g/m2). Ten patients with unilateral and one with bilateral lung metastases were treated by resection of metastases and chemotherapy. Three of these patients are alive. The overall long-term survival was 35%. From 1981 to September 1986, 32 patients were treated according to the T-10 regimen from Sloan Kettering Memorial Hospital in New York. Four patients died after major protocol violations and one patients was found dead in his home of unknown cause without tumour at autopsy. Few patients developed metastases. (The metastases appeared later and showed a different distribution in the body). Lung metastases were treated by resection and chemotherapy. In two patients bone metastases were treated by amputation. The overall survival after four years is 80%, but the number of patients observed for that time is small

  11. Clinical survey of prostate cancer

    International Nuclear Information System (INIS)

    Treatment trends and outcomes for prostate cancer in our hospital were reported. A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with prostatic specific antigen (PSA) elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p=0.0226), D (p=0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p=0.0027). In stage D2 patients, chemo-endocrine therapy with etoposide (VP-16), adriamycin (ADM) and cisplatin (CDDP) refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p=0.0467, P=0.0381). Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively. (author)

  12. Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

    International Nuclear Information System (INIS)

    There has been increasing interest in the use of heat in the treatment of cancer. Theoretically cells are the most sensitive to ionizing radiation at mitosis, whereas the cycle phase that is the most resistant to ionizing radiation namely late in the DNA. Synthetic phase (late S) is the most sensitive to hyperthermia. Hyperthermia has been reported to enhance the cytocidal effects of several active chemotherapeutic agents. When thermal potentiation of chemotherapeutic agents against malignant cells is contemplated, normal tissues have a relatively high ambient blood flow which increases in response to thermal stress, thereby dissipating heat, compared to tumors. Tumors, with relatively poor blood flow and a responsive neovasculature, are in capable of augmenting flow and acting as a heat reservoir. This is the phenomenon of a heat reservoir which is one factor to enhance the cytocidal effects of several active anticancer agents for enhancing the uptake in tumor. The importance is in the adjuvant chemotherapy treated for post operative, advanced and recurrent ovarian cancer. Heating enhances the effects of radiotherapy and chemotherapy. Thirty patients with ovarian cancer were subjected to the multidisciplinary treatment with combination of hyperthermochemotherapy and radiation. The 30 patients consisted of 18 with endometrioid adenocarcinoma and 7 with serious post operative or recurrent status. Two types of equipments with rediofrequencies of 70 MHz (BSD-1000) or 434 MHZ (TAG MED·HS 434) were used for hyperthermia. Chemotherapeutic agents such as adriamycin, cis DDP, cyclophosphamide and etoposide were injected intravenously. Arterial infusion with reservoir was very effective in advanced stage of ovarian cancer. No severe or fatal side effects were observed. Hyperthermochemotherapy is useful and effective for the postoperative management or the treatment of recurrent cancer of the ovary. (J.P.N.)

  13. Intensity-modulated radiotherapy and involved-node concept in patients with Hodgkin lymphoma: Experience of the Gustave-Roussy Institute; Optimisation de l''involved-node radiotherapy' par l'utilisation de la modulation d'intensite dans le lymphome hodgkinien localise: experience de l'institut Gustave-Roussy

    Energy Technology Data Exchange (ETDEWEB)

    Paumier, A.; Khodari, W.; Ghalibafian, M.; Blanchard, P.; Al Hamokles, H.; Bhari, M.; Lessard, N.; Girinsky, T. [Departement de radiotherapie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Beaudre, A. [Unite de physique, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France)

    2011-12-15

    Purpose. - To assess the clinical outcome of the involved-node radiotherapy concept with the use of intensity modulated radiotherapy (IMRT) in patients with localized supra-diaphragmatic Hodgkin lymphoma. Patients and methods. - Patients with early-stage supra-diaphragmatic Hodgkin lymphoma were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy (INRT) concept according to the EORTC guidelines. Intensity modulated radiotherapy was performed free-breathing. Results. - Forty-seven patients with Hodgkin lymphoma (44 patients with primary Hodgkin lymphoma and three patients with recurrent disease) entered the study from January 2003 to December 2010. The median age was 31 years (range 17 to 62). Thirty patients had stage I-IIA, 14 had stage I-IIB disease and three had relapse. Forty-two patients received three to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The median radiation dose to patients was 36 Gy (range: 20-40). Protection of various organs at risk was satisfactory. The median follow-up was 57.4 months (range: 5.4-94.3). For patients with primary Hodgkin lymphoma, the 5-year survival and 5-year progression-free survival rates were 96% (95% confidence interval: 80-99) and 92% (95% confidence interval: 78-97), respectively. None of the three patients with recurrent disease has relapsed. Recurrences occurred in three patients: one was in-field relapse and two were visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in one case. Conclusion. - Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the involved node irradiation concept and intensity modulated irradiation. (authors)

  14. Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis and necrosis induction.

    Science.gov (United States)

    Hayashi, Sachiko; Hatashita, Masanori; Matsumoto, Hideki; Shioura, Hiroki; Kitai, Ryuhei; Kano, Eiichi

    2006-11-01

    The effects of amrubicin (AMR) and its active metabolite, amrubicinol (AMROH), on the sensitivity of human lung adenocarcinoma A549 cells to ionizing radiation were investigated in vitro. Further, the kinetics of apoptosis and necrosis induction were also analyzed. The cytocidal effects of X-ray irradiation on A549 cells resulted in a low level of radiosensitivity with a D0 value of 12 Gy. The slopes of the survival curves in the exponential phase were plotted on semilogarithmic paper for radiation combined with AMR (2.5 microg/ml) and AMROH (0.02 microg/ml) treatment, and were shown to be approximately parallel to treatment with irradiation alone. The initial shoulder-shape portion of the survival curve for radiation alone, indicating the repair of sublethal damage, was reduced as compared to that for sequential combined treatment with AMR or AMROH. Sequential treatments with AMR or AMROH prior to ionizing radiation resulted in an additive radio-enhancement effect that reduced not only survival, but also the shoulder width. Fractionated irradiation with 2 Gy per fraction of A549 cells was carried out in vitro similar to that commonly performed in clinical radiotherapy and the radio-resistance of the cells was shown to be inhibited by AMR and AMROH. Similar to AMR and AMROH, adriamycin and etoposide (VP-16) are DNA topoisomerase II inhibitors. The effects of these 4 agents on cells that received X-ray irradiation were compared and all of the agents exhibited comparable radio-enhancement effects. The induction of apoptosis was investigated at 48 and 72 h after administration of AMROH, radiation or combined treatment, and apoptosis was not significantly induced after any of the treatments. We also examined the induction of necrosis, and found that the incidence of necrosis following combined treatment was approximately 2 times higher than that with either of the single treatments. PMID:17016621

  15. IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA hypermethylation.

    Science.gov (United States)

    Chen, Yuan; Cui, Tiantian; Knösel, Thomas; Yang, Linlin; Zöller, Kristin; Petersen, Iver

    2011-07-01

    Insulin-like growth factor binding protein 7 (IGFBP7) was considered a tumor suppressor gene in lung cancer. However, the mechanism responsible for the downregulation of this gene has not yet been fully understood. In this study, we analyzed the epigenetic inactivation of IGFBP7 expression in human lung cancer. We found that 14 out of 16 lung cancer cell lines showed decreased expression of IGFBP7 compared to control cells by real-time RT-PCR, and 42 out of 90 patients (46.7%) with primary lung tumor exhibited negative staining of IGFBP7 by immunohistochemistry analysis. The IGFBP7 expression could be restored by demethylation agent 5-aza-2'-deoxycytidine (DAC) in 7 cancer cell lines. Methylation status of IGFBP7 was further evaluated by bisulfite sequencing (BS) and methylation-specific-PCR (MSP). It turned out that low expression of IGFBP7 was associated with DNA methylation in lung cancer cell lines and in primary lung tumors (P=0.019). To explore the regulatory role of p53 on IGFBP7, we transfected a wild type p53 expression vector into lung cancer cell lines H1299, H2228, and H82. Forced expression of p53 increased IGFBP7 expression only in H82 harboring no IGFBP7 methylation, while transfection in combination with DAC induced the expression of IGFBP7 in H1299 and H2228, in which IGFBP7 was methylated. Additionally, treatment with p53 inducer adriamycin (ADR) alone or in combination with DAC increased the expression of IGFBP7 in the 3 cell lines. Our data suggest that IGFBP7 is inactivated in lung cancer by DNA hypermethylation in both lung cancer cell lines and primary lung tumors, and IGFBP7 might be regulated by p53 in lung cancer cells. PMID:21095038

  16. Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance

    Institute of Scientific and Technical Information of China (English)

    Ji-Heng Wang; Jing-Ping Du; Ying-Hai Zhang; Xiao-Jun Zhao; Ru-Ying Fan; Zhi-Hong Wang; Zi-Tao Wu; Ying Han

    2011-01-01

    AIM: To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy. METHODS: A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established,and the expression of PrPc, Bcl-2 and Bax was detected in these cells. Apoptosis was determined using Annexin V staining. Western blotting and immunohistochemistry were performed to detect the expression of PrPc in patients receiving chemotherapy and to explore the role of PrPc expression in predicting the chemosensitivity and the outcome of gastric cancer patients receiving chemotherapy. Follow-up was performed for 2 years. RESULTS: PrPc expression was increased with the increase in drug resistance. Bcl-2, together with PrPc, increased the level of anti-apoptosis of cancer cells. Increased PrPc expression predicted the enhanced level of anti-apoptosis and resistance to anticancer drugs. PrPc expression could be used as a marker for predicting the efficacy of chemotherapy and the prognosis of gastric cancer. Increased PrPc expression predicted both poor chemosensitivity and a low 2-year survival rate. Contrarily, low PrPc expression predicted favorable chemosensitivity and a relatively high 2-year survival rate.CONCLUSION: PrPc expression is associated with histological types and differentiation of gastric cancer cells; The PrPc expression level might be a valuable marker in predicting the efficacy of chemotherapy and the prognosis of gastric cancer patients receiving chemotherapy.

  17. microRNA let-7c is essential for the anisomycin-elicited apoptosis in Jurkat T cells by linking JNK1/2 to AP-1/STAT1/STAT3 signaling.

    Science.gov (United States)

    Zhou, Zhiwei; Lu, Xijian; Wang, Jin; Xiao, Jia; Liu, Jing; Xing, Feiyue

    2016-01-01

    Anisomycin, an antibiotic produced by Streptomyces griseolus, strongly induces apoptosis in various tumor cells in vitro, superior dramatically to adriamycin. The present study aims to elucidate its detailed mechanistic process. The results showed that anisomycin sufficiently promoted the apoptosis in human leukemic Jurkat T cells at a quite low dose. microRNA let-7c (let-7c) contributed to the anisomycin-induced apoptosis, which could be abrogated by the inactivation of JNK signaling. The let-7c over-expression and the addition of its mimics facilitated the activation of AP-1, STAT1 and Bim by linking JNK1/2 to AP-1/STAT1, but rather inhibited the activation of STAT3 and Bcl-xL by connecting JNK1/2 to STAT3, followed by the augmented apoptosis in the cells. The let-7c deficiency reduced the AP-1, STAT1 and Bim activities, and enhanced the STAT3 and Bcl-xL, alleviating the anisomycin-induced apoptosis. The knockdown of the bim gene repressed the anisomycin-boosted apoptosis through the attenuation of the active Bak and Bax. The findings indicate for the first time that miR let-7c is essential for the anisomycin-triggered apoptosis by linking JNK1/2 to AP-1/STAT1/STAT3/Bim/Bcl-xL/Bax/Bak signaling. This provides a novel insight into the mechanism by which anisomycin leads to the tumor cell apoptosis, potentially laying the foundations for its development and clinical application. PMID:27087117

  18. APOPTOSIS AND PROLIFERATION OF TUMOR CELLS IN LOCALLY ADVANCED CERVICAL CANCER AFTER NEOADJUVANT INTRAARTERIAL CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    朱雪琼; 岳天孚; 惠京; 张颖; 王德华

    2003-01-01

    Objective: Through observing the clinical response to neoadjuvant intraarterial chemotherapy in locally advanced cervical cancer and investigating the changes of p53 protein expression, proliferation and apoptosis of tumor cells after chemotherapy, to study the relationship between biological markers and chemotherapeutic response. Methods: 20 women with locally advanced squamous cervical cancer received consecutive infusion chemotherapy of five days of cisplatin and adriamycin via the superselective uterine artery. The response to chemotherapy was evaluated by gynecologic examination and ultrasonography 3 weeks after chemotherapy. The changes of apoptotic index (AI), proliferation index (PI) and p53 expression of tumor cells were detected by immunohistochemical technique. Results: The clinical response rate of locally advanced squamous cervical cancer to uterine artery infusion chemotherapy was 70%. No change of PI was found 3 weeks after treatment, but AI significantly increased from 2.79±0.76 to 4.29±1.13 (P<0.01), and AI/PI from 5.68±1.21 to 9.00±1.95 (P<0.05). On the contrary, the expression of p53 was significantly decreased (P<0.05). Patients who responded to chemotherapy showed higher PI before chemotherapy and significantly increased AI and AI/PI after chemotherapy than non-responders (P<0.05). Conclusion: Higher PI was an indication for neoadjuvant intraarterial chemotherapy. One more cycle of chemotherapy should be given to those who have significantly increased AI or AI/PI after chemotherapy, while definite treatment such as surgery or/and radiotherapy should be immediately given to those patients without increased AI or AI/PI.

  19. [Ph1 positive acute lymphoblastic leukemia with DIC after operation of colon and lung cancer].

    Science.gov (United States)

    Yashige, H; Fujii, H

    1989-07-01

    We reported a rare case of triple cancers with acute lymphoblastic leukemia (ALL) associated with disseminated intravascular coagulopathy (DIC) after the operations of colon cancer and primary lung cancer. A 78-year-old Japanese male, who had been operated upon for colon cancer (adenocarcinoma) on March 1981, metastatic brain tumor (adenocarcinoma) on December 1986, and primary lung cancer (squamous cell carcinoma) on February 1987, was admitted to our hospital because of severe general malaise on December 6 1987. On admission, he had mild hepatosplenomegaly and hemorrhage diathesis such as purpura. Serum LDH increased to 2,515 mU/ml. The white blood cell count was 6,210/microliters with 53% leukemia cells, and the platelet count was 12,000/microliters. A bone marrow was infiltrated with 96.0% leukemia cells. The leukemia cells stained positively for PAS and negatively for peroxidase. Immunological examination of leukemia cells showed that HLA-DR, TdT, B1 and J5 were positive and cytoplasmic Igmu and surface Ig were negative, indicating common ALL. The coagulation studies revealed that the activated partial thromboplastin time was prolonged to 42.0 seconds, FDP increased to 79.9 micrograms/ml, and antithrombin-III decreased to 62%. Chromosome analysis showed a 48, XY, +2, +21q-, t(9;22) karyotype. He was diagnosed as having Ph1 positive ALL associated with DIC. He was treated with vindesine, prednisolone, L-asparaginase, and adriamycin and complete remission (CR) was achieved after two months. But on August 1988, 8 months after CR, ALL and brain tumor relapsed and he died of pneumonia on September 19, 1988. PMID:2810793

  20. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  1. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

  2. Dual drug delivery using 'smart' liposomes for triggered release of anticancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-07-15

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-{alpha}) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG{sub 2000}-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG{sub 2000}-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 {+-} 0.5 Degree-Sign C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 {+-} 1 Degree-Sign C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI{sub 50} = 6.5 {mu}g/ml) than positive control (Adriamycin, GI{sub 50} = 9.1 {mu}g/ml) and FR-targeted PEGylated liposomes GI{sub 50} (14.7 {mu}g/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called 'smart liposomes' which has not only mediated effective targeting to FR-{alpha} but also triggered release of drugs upon hyperthermia.

  3. Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

    Directory of Open Access Journals (Sweden)

    Chabita Saha

    Full Text Available Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q. The present study deals with the synthesis and characterisation of nano formulations (NFs from Q loaded PLGA (poly lactic-co-glycolic acid nano particles (NPs by surface modification. The surface of Q-loaded (NPs is modified by coating with biopolymers like bovine serum albumin (BSA or histones (His. Conventional chemotherapeutic drugs adriamycin (ADR and mitoxantrone (MTX are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400-500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR by reaching and treating the target cancerous cells by virtue of size, charge and retention.

  4. Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

    Science.gov (United States)

    Saha, Chabita; Kaushik, Agrima; Das, Asmita; Pal, Sandip; Majumder, Debashis

    2016-01-01

    Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400-500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention. PMID:27196562

  5. Treatment results in advanced stage Hodgkin′s lymphoma: A retrospective study

    Directory of Open Access Journals (Sweden)

    H Jain

    2015-01-01

    Full Text Available Background: Hodgkin′s lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. Aim: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. Materials and Methods: This retrospective study included de-novo advanced stage HL patients (≥15 years registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS and progression-free survival (PFS. Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. Results: There were 125 patients (males 77% who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years. Stage IV disease was seen in (46 patients 37%; 75% (94 patients patients had B symptoms. International prognostic score (IPS ≤4 was seen in 95/112 (85% patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients. Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4 were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. Conclusions: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

  6. Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, L. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Oezker, K. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Hayward, M. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Akansel, G. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Griffith, O. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Isitman, A.T. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Hellman, R. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States); Collier, D. [Dept. of Nuclear Medicine and Biochemistry, Medical College of Wisconsin, Milwaukee, WI (United States)

    1996-05-01

    An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both BIBI and {sup 201}Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%{+-}0.5% vs 3.1%.0.6%; P<0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%; P<0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2{+-}81.1 nmol/mg protein to 17.6{+-}4.4 nmol/mg protein; P<0.001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%{+-}0.5% and 5.93%{+-}1.7%, respectively; P>0.1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarly indicate that a cancer is sensitive to drugs. (orig.)

  7. Disruption of a GATA4/Ankrd1 signaling axis in cardiomyocytes leads to sarcomere disarray: implications for anthracycline cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Billy Chen

    Full Text Available Doxorubicin (Adriamycin is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1 is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4 in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent

  8. The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors.

    Science.gov (United States)

    Li, Wei; Li, Jinfeng; Gao, Jie; Li, Bohua; Xia, Yu; Meng, Yanchun; Yu, Yongsheng; Chen, Huaiwen; Dai, Jianxin; Wang, Hao; Guo, Yajun

    2011-05-01

    Focusing on high temperature and low pH of tumor tissue, we prepared temperature and pH responsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-lacitde) (PID(118)-b-PLA(59)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-ε-caprolactone) (PID(118)-b-PCL(60)) diblock copolymers with symmetric hydrophobic blocks by the reversible addition-fragmentation chain transfer (RAFT). The corresponding dual functional polymeric micelles were fabricated by dialysis methods. Their well-defined core-shell structure was characterized by (1)H NMR in D(2)O and further confirmed by TEM. Their structural and physical chemistry properties such as diameters (D), core corona dimension (R(core), R(shell)), distribution (PDI), M(w), aggregation number (N(agg)), second virial coefficient (A(2)), critical micellization concentration (CMC) and z-potential were firstly systemically investigated by dynamic and static laser light scattering. The volume phase transition temperature (VPTT) was around 40 °C above which the intracellular uptake of adriamycin (ADR) was significantly enhanced. Both flow cytometry and fluorescent microscopy showed that the ADR transported by these micelles was about 4 times higher than that by the commercial ADR formulation Taxotere®. In vitro cytotoxicity assay against N-87 cancer cell and confocal laser scanning microscopy (CLSM) also confirmed such promoting efficiency. In addition, it was interesting to find that cell surviving bounced back as T = 42 °C due to the inter-micellar aggregation. The well clarified mechanism strongly support that our finely tailored dual functional core-shell micelles are potent in enhancing cellular uptake and drug release. PMID:21377724

  9. EFFECT OF OCIMUM IN CHEMOTHERAPY INDUCED OXIDATIVE STRESS” A STUDY CONDUCTED IN DAKSHINA KANNADA DISTR ICT, KARNATAKA, INDIA

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    Debkumar

    2012-11-01

    Full Text Available ABSTRACT : Adriamycin (ADR belongs to anthracycline group of antibiotics, which is widely used for the complete remission of solid tumours. I n carcinoma breast, non Hodgkin’s lymphoma and Hodgkin’s lymphoma, ADR is considered as most useful chemotherapeutic medication. Anthracycline by virtue of their quinon e group generates free radicals in solution in both normal and malignant cells. The Ocimum leaf ex tract as well as their flavonoids orientin and vicenin have strong antioxidant activity in vit ro and antilipid peroxidative effect in vivo, and strongly suggest free radical scavenging as a major mechanism by which Ocimum products protect against cellular damage and tumour induction . However, most interest has been devoted to the antioxidant activity of flavonoids, which is due to their ability to reduce free radical formation and to scavenge free radicals. Th e capacity of flavonoids to act as antioxidants in vitro has been a subject of several studies in t he past years. The antioxidant efficacy of flavonoids present in Ocimum sanctum in vivo is less documented, presumably because of the limited knowledge on their uptake in tumours. Inspite of limitation of the knowledge of exact mechanism of uptake of flavonoids we have studied an tioxidant efficacy of Ocimum sanctum aqueous extract (140mg with placebo control in carc inoma breast, non Hodgkin’s lymphoma, Hodgkin’s lymphoma cases along with chemotherapy parti cularly during third cycle. Statistical analysis has been done by Mann Whitney’s test which shows no significant difference of antioxidant enzymes between study (n=19 and contro l (n=16 group before chemotherapy. There is a significant increase of all scavenging e nzymes in study group (n=19 compared to control group (n=16 after chemotherapy. Significant increase in the Haemoglobin content and enhanced activities of Superoxide dismutase ( SOD a nd Catalase (CAT in the study group which was given Ocimum

  10. Waldenström makroglobulinemili hastada rituksimab tedavisi sonrası gelişen gizli hepatit B reaktivasyonu

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    Vedat Aslan

    2012-12-01

    Full Text Available The anti-CD20 monoclonal antibody rituximab has beenused extensively in the treatment of B-cell lymphoma.Several studies reported hepatitis B virus (HBV reactivationafter rituximab. The majority of these cases havebeen described in chronic carriers of HBV, whereas reactivationin occult hepatitis B virus (OHBV carriers mayoccur.The presented case with the diagnosis of Waldenström’smacroglobulinemia was HBsAg negative and anti HBcIgGpositive before chemotherapy. The patient was started onCVP (cyclophosphamide, vincristine, prednisolone chemotherapy.However, no clinical or laboratory responsewas obtained and the patient was considered unresponsiveto three cycles of CVP therapy. Therefore R-CHOP(rituximab, cyclophosphamide, adriamycin, vincristineand prednisolone was planned as the second therapy.Laboratory work-up after the first cycle of R-CHOP therapyrevealed an aspartate aminotransferase (AST levelof 267 U/L and alanine aminotransferase (ALT level of318 U/L. HBsAg and anti HBcIgG were positive and HBVDNA was 56400 IU/ml. Lamivudin 100 mg/day was started.Four weeks after the initiation of lamivudin therapy,ALT and AST levels returned to normal. Currently, the patienthas received the fourth cycle of R-CHOP therapy.ALT and AST levels continue to be in normal range. Thiscondition was considered to be the reactivation of OHBVfollowing rituximab.The aim of this case presentation is to call attention toHBV reactivation possibility in cases taking immunosupressivemedications like Rituximab. J Clin Exp Invest2012; 3(4: 541-544Key words: Waldenström’s macroglobulinemia, rituximab,occult HBV infection

  11. The benefit of cisplatin-based polychemotherapy for adenocarcinoma of the lung. The Kyushu Lung Cancer Chemotherapy Study Group.

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    Hara, N; Ohta, M; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

    1990-01-01

    We studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant (P less than 0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%; P less than 0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm (P less than 0.035, Wilcoxon-Gehan test; P less than 0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months; P less than 0.025, Wilcoxon-Gehan test; P less than 0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm (P less than 0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy. PMID:2108816

  12. Quality of Life and Neutropenia in Patients with Early Stage Breast Cancer: A Randomized Pilot Study Comparing Additional Treatment with Mistletoe Extract to Chemotherapy Alone

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    Wilfried Tröger

    2009-01-01

    Full Text Available Background: Chemotherapy for breast cancer often deteriorates quality of life, augments fatigue, and induces neutropenia. Mistletoe preparations are frequently used by cancer patients in Central Europe. Physicians have reported better quality of life in breast cancer patients additionally treated with mistletoe preparations during chemotherapy. Mistletoe preparations also have immunostimulant properties and might therefore have protective effects against chemotherapy-induced neutropenia.Patients and Methods: We conducted a prospective randomized open label pilot study with 95 patients randomized into three groups. Two groups received Iscador® M special (IMS or a different mistletoe preparation, respectively, additionally to chemotherapy with six cycles of cyclophosphamide, adriamycin, and 5-fluoro-uracil (CAF. A control group received CAF with no additional therapy. Here we report the comparison IMS (n = 30 vs. control (n = 31. Quality of life including fatigue was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30. Neutropenia was defined as neutrophil counts <1,000/µl and assessed at baseline and one day before each CAF cycle.Results: In the descriptive analysis all 15 scores of the EORTC-QLQ-C30 showed better quality of life in the IMS group compared to the control group. In 12 scores the differences were significant (p < 0.02 and nine scores showed a clinically relevant and significant difference of at least 5 points. Neutropenia occurred in 3/30 IMS patients and in 8/31 control patients (p = 0.182.Conclusions: This pilot study showed an improvement of quality of life by treating breast cancer patients with IMS additionally to CAF. CAF-induced neutropenia showed a trend to lower frequency in the IMS group.

  13. Experimental study of interventional infusion thermochemotherapy in rabbit liver VX2 tumor

    International Nuclear Information System (INIS)

    Objective: Effectiveness of two kinds of thermochemotherapy infusion from intraarterial approach were studied in the grafted liver VX2 tumors of rabbit. Methods: VX2 tumor model was established in 30 Newzland rabbit's livers. Percutaneous transfemoral hepatic arterial catheterization with fixation of the catheter tip inside the feeding vessel was carried out under DSA guidance. All 30 rabbits were divided into three groups (n=10 in each group), normal temperature 100 ml saline + Adriamycin (ADM) infusion (group 1), 60 degree C 100 ml saline + ADM continuous perfusion (group 2) and 60 degree C 100 ml saline + ADM intermittent perfusion (group 3). After the perfusion, the lasting time periods of 43-45 degree C for tumor tissue of group 2 and 3 together with the concentrations of ADM within tumor's tissue were measured. Results: Concentrations of ADM were shown as (12.013 ± 2.237) μg/ml, (17.622 ± 1.368) μg/ml, and (11.519 ± 1.225) μg/ml for group 2, group 3 and group 1 respectively. 60 degree C intermittent perfusion vs 60 degree C continuous perfusion showed P0.05. 43-45 degree C period lasting time (min) for 60 degree C continuous perfusion vs 60 degree C intermittent perfusion were (4.1 ± 2.7) min and (11.3 ± 3.3) min respectively, the latter was three times more than the former. There were no differences shown between the temperature, respiration and heart rate of group 2 and group 3. Conclusion: Intermittent intraarterial perfusion thermochemocherapy is a more effective interventional management among all thermochemotherapies. (authors)

  14. Clinical evaluation of reduced MIBG uptake in the infero-posterior segments

    International Nuclear Information System (INIS)

    The quantitative assessment of the reduced uptake of 123I-MIBG in the in fero-posterior segments was investigated. The subjects were 135 patients with non-ischemic heart disease (AR: aortic regurgitation, MR: mitral regurgitation, DCM: dilated cardiomyopathy, HCM: hypertrophic cardiomyopathy, ADR: adriamycin-induced myocardial damage, HHD: hypertensive heart disease) who underwent MIBG myocardial scintigraphy at rest. Anterior planar and SPECT were obtained initial images and delayed images. The heart-to-mediastinum activity ratio (H/M) was calculated from the delayed planar image, and the mean MIBG clearance was calculated with bull's eye displays obtained from the initial and the delayed SPECT images. The bull's eye display, obtained from the delayed SPECT images was evaluated by generating a blacked out map which exhibited regions with reduced % uptake under mean -2 SD of normal controls. The blacked out regions involved the infero-posterior segments and were closely resembled to the sector form. The central angle of this sector was named the angle of defect (AOD). This AOD was compared with H/M, the clearance, the NYHA class and echocardiographic findings of the patients. AOD was significantly correlated with both H/M and the clearance in each heart disease, and AOD was significantly higher in NYHA class III than in class II and higher in class II than in class I. AOD was significantly correlated with the end-systolic dimension, the atrial dimension and the ejection fraction in patients with AR, MR and DCM, respectively. H/M and the clearance have been widely used as quantitative indices in MIBG myocardial scintigraphy. (K.H.)

  15. Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules

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    Keane, W.F.; Raij, L.

    1985-06-01

    Clinical and experimental studies suggest that accumulation of phlogogenic macromolecules in the glomerular mesangium may lead to mesangial expansion and eventual glomerulosclerosis. In focal glomerulosclerosis and nephrotic syndrome entrapment of macromolecules is observed in areas of glomerulosclerosis. To determine whether mesangial uptake of radiolabeled, heat-aggregated IgG (AG/sup 125/I), a biologically active macromolecular protein, is influenced by increased glomerular filtration barrier permeability, the authors evaluated the glomerular uptake of AG/sup 125/I in three models of proteinuria: aminonucleoside of puromycin nephropathy (PAN), adriamycin nephropathy, and Heyman's nephropathy. Rats were studied approximately 1 week after onset of proteinuria. AG/sup 125/I was measured in preparations of isolated glomeruli and compared to simultaneous blood, liver, and spleen levels. Only rats with PAN had a marked increase in glomerular AG/sup 125/I compared to control rats, 7.8 versus 2.6 micrograms/mg of glomeruli, respectively. The authors then evaluated whether a continuous infusion of a competitive inhibitor of angiotensin II, saralasin (300 micrograms/kg of body weight/minute), influenced mesangial uptake of AG/sup 125/I in PAN rats. Strikingly, glomerular AG/sup 125/I in rats with PAN was reduced to levels comparable to that observed in control rats infused with only saralasin, 2.8 versus 3.0 micrograms/mg of glomeruli, respectively. This effect on glomerular AG/sup 125/I content was independent of any significant effect of saralasin on blood, hepatic, or splenic levels of AG/sup 125/I. Moreover, these changes in glomerular AG/sup 125/I in saralasin-infused rats with PAN did not appear to directly correlate with changes in whole kidney function.

  16. Bladder Preservation by Combined Modality Therapy for Invasive Bladder Cancer: A Five-Year Follow-up

    International Nuclear Information System (INIS)

    Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materials : From 1991 Jan, through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated width induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of al patients was 70 months. Results : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was 67.3%. Complete remission rate was 80% (20/25). Sixth-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a 67.3% overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages. Sixty-three percent of long term survivors preserved their bladders

  17. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

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    SONG, KUI; LI, MIN; XU, XIAOJUN; XUAN, LI; HUANG, GUINIAN; LIU, QIFA

    2016-01-01

    Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose transporter (GLUT)1, and hexokinase-II was measured by quantitative polymerase chain reaction. The levels of LDH and β subunit of human F1-F0 adenosine triphosphate synthase (β-F1-ATPase) were detected by enzyme-linked immunosorbent and western blot assays. The HL-60 and HL-60/ADR cell lines were used to evaluate glycolytic activity and effect of glycolysis inhibition on cellular proliferation and apoptosis. Drug-resistant HL-60/ADR cells exhibited a significantly increased level of glycolysis compared with the drug-sensitive HL-60 cell line. The expression of HIF-1α, hexokinase-II, GLUT1 and LDH were increased in AML patients with no remission (NR), compared to healthy control individuals and patients with complete remission (CR) and partial remission. The expression of β-F1-ATPase in patients with NR was decreased compared with the expression in the CR group. Treatment of HL-60/ADR cells with 2-deoxy-D-glucose or 3-bromopyruvate increased in vitro sensitivity to Adriamycin (ADR), while treatment of HL-60 cells did not affect drug cytotoxicity. Subsequent to treatment for 24 h, apoptosis in these two cell lines showed no significant difference. However, glycolytic inhibitors in combination with ADR increased cellular necrosis. These findings indicate that increased glycolysis and low efficiency of oxidative phosphorylation may contribute to drug resistance. Targeting glycolysis is a viable strategy for modulating chemoresistance in AML.

  18. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    International Nuclear Information System (INIS)

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  19. Intensity-modulated radiotherapy and involved-node concept in patients with Hodgkin lymphoma: Experience of the Gustave-Roussy Institute

    International Nuclear Information System (INIS)

    Purpose. - To assess the clinical outcome of the involved-node radiotherapy concept with the use of intensity modulated radiotherapy (IMRT) in patients with localized supra-diaphragmatic Hodgkin lymphoma. Patients and methods. - Patients with early-stage supra-diaphragmatic Hodgkin lymphoma were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the involved-node radiotherapy (INRT) concept according to the EORTC guidelines. Intensity modulated radiotherapy was performed free-breathing. Results. - Forty-seven patients with Hodgkin lymphoma (44 patients with primary Hodgkin lymphoma and three patients with recurrent disease) entered the study from January 2003 to December 2010. The median age was 31 years (range 17 to 62). Thirty patients had stage I-IIA, 14 had stage I-IIB disease and three had relapse. Forty-two patients received three to six cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The median radiation dose to patients was 36 Gy (range: 20-40). Protection of various organs at risk was satisfactory. The median follow-up was 57.4 months (range: 5.4-94.3). For patients with primary Hodgkin lymphoma, the 5-year survival and 5-year progression-free survival rates were 96% (95% confidence interval: 80-99) and 92% (95% confidence interval: 78-97), respectively. None of the three patients with recurrent disease has relapsed. Recurrences occurred in three patients: one was in-field relapse and two were visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in one case. Conclusion. - Our results suggest that patients with localized Hodgkin lymphoma can be safely and efficiently treated using the involved node irradiation concept and intensity modulated irradiation. (authors)

  20. Chemotherapy of WAP-T mouse mammary carcinomas aggravates tumor phenotype and enhances tumor cell dissemination.

    Science.gov (United States)

    Jannasch, Katharina; Wegwitz, Florian; Lenfert, Eva; Maenz, Claudia; Deppert, Wolfgang; Alves, Frauke

    2015-07-01

    In this study, the effects of the standard chemotherapy, cyclophosphamide/adriamycin/5-fluorouracil (CAF) on tumor growth, dissemination and recurrence after orthotopic implantation of murine G-2 cells were analyzed in the syngeneic immunocompetent whey acidic protein-T mouse model (Wegwitz et al., PLoS One 2010; 5:e12103; Schulze-Garg et al., Oncogene 2000; 19:1028-37). Single-dose CAF treatment reduced tumor size significantly, but was not able to eradicate all tumor cells, as recurrent tumor growth was observed 4 weeks after CAF treatment. Nine days after CAF treatment, residual tumors showed features of regressive alterations and were composed of mesenchymal-like tumor cells, infiltrating immune cells and some tumor-associated fibroblasts with an intense deposition of collagen. Recurrent tumors were characterized by coagulative necrosis and less tumor cell differentiation compared with untreated tumors, suggesting a more aggressive tumor phenotype. In support, tumor cell dissemination was strongly enhanced in mice that had developed recurrent tumors in comparison with untreated controls, although only few disseminated tumor cells could be detected in various organs 9 days after CAF application. In vitro experiments revealed that CAF treatment of G-2 cells eliminates the vast majority of epithelial tumor cells, whereas tumor cells with a mesenchymal phenotype survive. These results together with the in vivo findings suggest that tumor cells that underwent epithelial-mesenchymal transition and/or exhibit stem-cell-like properties are difficult to eliminate using one round of CAF chemotherapy. The model system described here provides a valuable tool for the characterization of the effects of chemotherapeutic regimens on recurrent tumor growth and on tumor cell dissemination, thereby enabling the development and preclinical evaluation of novel therapeutic strategies to target mammary carcinomas. PMID:25449528

  1. The β isoform of GSK3 mediates podocyte autonomous injury in proteinuric glomerulopathy.

    Science.gov (United States)

    Li, Changbin; Ge, Yan; Dworkin, Lance; Peng, Ai; Gong, Rujun

    2016-05-01

    Converging evidence points to glycogen synthase kinase (GSK) 3 as a key player in the pathogenesis of podocytopathy and proteinuria. However, it remains unclear if GSK3 is involved in podocyte autonomous injury in glomerular disease. In normal kidneys, the β isoform of GSK3 was found to be the major GSK3 expressed in glomeruli and intensely stained in podocytes. GSK3β expression in podocytes was markedly elevated in experimental or human proteinuric glomerulopathy. Podocyte-specific somatic ablation of GSK3β in adult mice attenuated proteinuria and ameliorated podocyte injury and glomerular damage in experimental adriamycin (ADR) nephropathy. Mechanistically, actin cytoskeleton integrity in podocytes was largely preserved in GSK3β knockout mice following ADR insult, concomitant with a correction of podocyte hypermotility and lessened phosphorylation and activation of paxillin, a focal adhesion-associated adaptor protein. In addition, GSK3β knockout diminished ADR-induced NFκB RelA/p65 phosphorylation selectively at serine 467; suppressed de novo expression by podocytes of NFκB-dependent podocytopathic mediators, including B7-1, cathepsin L, and MCP-1; but barely affected the induction of NFκB target pro-survival factors, such as Bcl-xL. Moreover, the ADR-elicited podocytopenia and podocyte death were significantly attenuated in GSK3β knockout mice, associated with protection against podocyte mitochondrial damage and reduced phosphorylation and activation of cyclophilin F, a structural component of mitochondria permeability transition pores. Overall, our findings suggest that the β isoform of GSK3 mediates autonomous podocyte injury in glomerulopathy by integrating multiple podocytopathic signalling pathways. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26876299

  2. The choice of regimens based on bortezomib for patients with newly diagnosed multiple myeloma.

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    Jingsong He

    Full Text Available INTRODUCTION: Bortezomib has significantly improved multiple myeloma (MM response rates, but strategies for choosing bortezomib-based regimens for initial MM therapy are not standardized. Here, we describe four bortezomib-based therapies in Chinese MM patients to determine the optimal chemotherapeutic approach. METHODS: Newly diagnosed symptomatic MM patients at three hematological centers between February 1, 2006 and May 31, 2013 were treated with therapies including bortezomib plus dexamethasone (PD or combinations of PD with either adriamycin (PAD, cyclophosphamide (PCD or thalidomide (PTD for every 28 days. RESULTS: The overall response rate of all the 215 eligible patients was 90.2%. The ORR for PCD, PAD, PTD and PD were 97.4%, 93.2%, 85.3% and 77.8% while the effects with VGPR or better were 63.7%, 62.7%, 44.2% and 37.8%, respectively. The effect of ORR, VGPR and CR/nCR for the PCD regimen was better than the PD protocol. Median PFS for all patients was 29.0 months with significant differences observed among treatment groups. Median OS of all the patients was not reached, but three-drug combinations were superior to PD alone. Frequently observed toxicities were neutropenia, thrombocytopenia, fatigue, infection, herpes zoster, and peripheral neuropathy. The incidence of peripheral neuropathy (PN in PTD group was significantly higher than other three groups, especially grade 2-3 PN. Treatment with anti-viral agent acyclovir significantly reduced the incidence of herpes zoster. CONCLUSIONS: Our experience indicated that bortezomib-based regimens were effective and well-tolerated in the Chinese population studied; three-drug combinations PCD, PAD were superior to PD, especially with respect to PCD.

  3. Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana.

    Science.gov (United States)

    Jayaprakasam, Bolleddula; Seeram, Navindra P; Nair, Muraleedharan G

    2003-01-10

    Bioassay-guided purification of an extract of Cucurbita andreana fruits yielded cucurbitacins B (1), D (2), E (3), and I (4). These cucurbitacins were evaluated for their inhibitory effects on the growth of human colon (HCT-116), breast (MCF-7), lung (NCI-H460), and central nervous system (CNS) (SF-268) cancer cell lines, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and on lipid peroxidation. Inhibitory activities of cucurbitacins B (1), D (2), E (3) and I (4), respectively, were for colon 81.5, 80.4, 77, and 65% at 0.4 microM, breast 87, 78, 66.5, and 12% at 0.4 microM, lung 96, 43, 37 and 2% at 0.1 microM and CNS 92, 25, 24 and 4% at 0.05 microM. Adriamycin (doxorubicin) was used as a positive control, which showed 64, 47, 45 and 71% inhibition of HCT-116 (colon), MCF-7 (breast), NCI-H460 (lung) and SF-268 (CNS) cell lines, respectively, at 0.3 x 10(-5) M. Compounds 1, 2, 3, and 4 inhibited the COX-2 enzyme by 32, 29, 35, and 27%, respectively, at 100 microg/ml. However these compounds did not inhibit the COX-1 enzyme at this concentration. Ibuprofen, naproxen and vioxx, commercial antiinflammatory drugs, were tested as controls for the inhibition of COX-1 and COX-2 enzymes at concentrations of 2.1, 2.5 and 1.67 microg/ml, respectively. Ibuprofen and naproxen exhibited 59 and 95% COX-1, and 53 and 79% COX-2 inhibitory activities, respectively. Vioxx showed specific COX-2 inhibition by 71%. Also, cucurbitacins 1 and 4 inhibited lipid peroxidation by 59 and 23%, respectively, at 100 microg/ml. PMID:12445672

  4. The effect of TACE with endostatin on hemodynamics in hepatic implantation tumor using Doppler ultrasonography

    International Nuclear Information System (INIS)

    Objective: To investigate the hemodynamic changes in the rabbit liver and VX2 hepatic implantation tumor after treatment by transcatheter arterial chemoembolization (TACE)/endostatin using Doppler ultrasonography. Methods: Twenty rabbits with VX2 hepatic tumor were randomly distributed into the control group (n=10) and the anti- angiogenesis group (n=10). The rabbits were administered with endostatin and adriamycin-lipiodol in the anti-angiogenesis group and with 37℃ saline in the control group via hepatic artery. The hemodynamic changes of the tumors, hepatic artery, and portal vein were recorded with Doppler ultrasonography 1 week after the treatment. The results before and after the treatment were compared. Results: In the control group, the maximal hepatic artery blood flow velocity was significantly higher than that before the treatment (P<0.05). However, the resistance index and the portal vein blood flow velocities had no significantly change compared with those before the treatment (P>0.05). In the anti-angiogenesis group, the hepatic artery blood flow velocity was significantly lower than that before the treatment (P<0.05), and the resistance index was increased (P<0.05). However, the portal vein blood flow velocity had no significantly change (P>0.05). The blood flow signal in all tumors was rich before embolization. After TACE, the blood flow signal was significantly decreased, even partly disappeared in the anti-angiogenesis group. Conclusion: TACE with endostatin can effectively block the blood supplement of VX2 hepatic implantation tumor. Doppler ultrasonography can detected the blood flow changes and can be used in evaluating the therapeutic effect in hepatic implantation tumor. (authors)

  5. Radiolabelled phage display peptide derivatives inhibiting matrix metalloproteinases target xenografted tumors in mice

    International Nuclear Information System (INIS)

    Background: A phage display peptide has been characterized, which inhibits matrix metalloproteinase activity, and cell migration. This cyclic decapeptide Cys-Thr-Thr-His-Trp-Gly-Phe-Thr-Leu-Cys is known to inhibit tumor growth both in preincubated cells with peptide and also in vivo. Cell killing has been demonstrated in vitro utilizing peptidoliposome construct which contained adriamycin. Furthermore, tumor targeting using direct labelling with Tc-99m has demonstrated. Materials and Methods: Now wide variety of peptide derivatives of this CTTHWGFTLC peptide has been constructed and they alter by lipophilicity. The biodistribution of labelled peptides containing AAY and GRENYCH residues in the amino terminus has been studied in normal and tumor bearing mice. Labeling method for In-111 has been cDTPA and for iodination direct labelling and indirect ATE method. Results: Direct labeling retained the lipofilicity of the peptide. Indirect labeled peptides were more hydrophobic and their distribution were different compared to direct labeled peptides. These radiolabelled peptides both with In-111 and I-125 retained in vitro inhibitory activity. The biostribution data demonstrated liver uptake with the lipophilic and more kidney uptake with the more hydrophilic constructs. Tumor targeting was demonstrated in nude mice. Conclusion: Because of excellent in vitro characteristics in tumor targeting, and inhibition of the endothelium of tumor vasculature, and inhibition of tumor growth with the cold peptide, these radiolabelled peptides have potential for further development. This tumor targeting peptidoliposomes as drug carrier may be used cancer treatment utilizing multi potential approach: radionuclide therapy, invasion inhibition and cell killing

  6. Effects of Intensive Induction Chemotherapy on Consolidation Radiotherapy in Young Children with High-risk Hodgkin Lymphoma%高危霍奇金淋巴瘤低龄患儿高强度诱导化疗对巩固放疗的影响

    Institute of Scientific and Technical Information of China (English)

    徐诣芝; 孙艳; 郑宝敏; 罗治彬

    2015-01-01

    OBJECTIVE:To investigate the safety of induction chemotherapy and the implementation method of consolidation radiotherapy in young children with high-risk Hodgkin lymphoma(HL),by evaluating the effects of intensive induction chemother-apy on consolidation radiotherapy. METHODS:Six pediatric patients with high-risk HL received low-dose involved field radiation therapy (IFRT) via volumetric modulated arc therapy (VMAT) following 6 cycles of intensive chemotherapy [Ara-C/VP16 (cyto-sine arabinoside+etoposide),ABVE-PC(adriamycin+bleomycin+leurocristine+etoposide+metacortandracin+cyclophosphamide)and CHOP(cyclophosphamide+leurocristine+adriamycin+ prednisone)in turn]. Therapeutic efficacy and toxic effects were evaluated af-ter treatment. RESULTS:Intensive induction chemotherapy and consolidation radiotherapy were acceptable by young children,and mild acute or subacute toxic reaction were observed. Intensive induction chemotherapy didn’t affect toxic effects of consolidation ra-diotherapy. In this regimen,the cumulative doses of bleomycin and adriamycin were 20 mg/m2 and 270 mg/m2,respectively. VMAT optimized plan to ensure that the dose that involved organs received was safe. In the patient with mediastional radiation therapy,the mean lung and heart doses were 525.6 cGy and 503.9 cGy,respectively. CONCLUSIONS:It is safe to give high-risk HL young children 6 cycles of intensive induction chemotherapy(Ara-C/VP16,ABVE-PC and CHOP in turn)before radiotherapy. It is feasi-ble to conduct IFRT with 18-20 Gy and an additional 20-25 Gy boost,1.5-1.8 Gy/fraction. VMAT deserves to be advised.%目的:通过评估高危霍奇金淋巴瘤(HL)低龄患儿高强度诱导化疗对巩固放疗的影响,探讨诱导化疗药物的安全性及巩固放疗的有效实施方法。方法:对6例高危HL患儿,采用阿糖胞苷+依托泊苷(Ara-C/VP16)、阿霉素+博来霉素+长春新碱+依托泊苷+泼尼松+环磷酰胺(ABVE-PC)和环磷酰胺+长春

  7. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  8. Preliminary study of the transcatheter arterial chemoembolization in combination of percutaneous injection of chemoembolization agent intra-portal vein tumor thrombosis in treatment of primary hepatic carcinoma accompanied by portal vein tumor thrombosis

    International Nuclear Information System (INIS)

    Objective: To assess the therapeutic outcomes of transcatheter arterial chemoembolization combined with percutaneous injection of chemoembolization agent intra-portal vein tumor thrombosis for primary hepatic carcinoma accompanied by portal vein tumor thrombus. Methods: Thirty patients with primary hepatic carcinoma accompanied by portal vein tumor thrombosis of type II and type III were randomly divided into two groups. The Child-Pugh ratings (class A and B) of group A and B were 9 vs 9 (class A) and 5 vs 7 (class B) respectively (χ2=0.201, P>0.05). The constitution of Type II and type III portal vein tumor thrombus in group A and B were 8 vs 9 and 6 vs 7 respectively (χ2= 0.002, P>0.05). The median values of ALT, TBIL, ALB and AFP in group A and B were 58.7U/L vs 70.5 U/L (W=191.5, P>0.05), 21.4 μmol/L vs 21.7 μmol/L (W=203, P>0.05), 35.3 g/L vs 37.5 g/L (W=214,P>0.05) and 680 μg/L vs 873 μg/L (W=179.00, P>0.05) respectively. Group A was treated with transcatheter arterial chemoembolization (TACE) using emulsion made up of adriamycin, cisplatin, mitomycin and ultraliquidlipiodol plus percutaneous injection of chemoembolization agent intra- portal vein tumor thrombosis using emulsion consisted of cisplatin and ultraliquidlipiodol, while group B was treated with TACE only as a control group. Survival analyses were performed via the Kaplan-Meier test in SPSS11.5 with the log-rank tests with an threshold of 0.05. Results: The 3, 6 and 12 months survival cases of group A and B were 11 vs 10, 10 vs 3, and 7 vs 0 respectively. The median survival time of group A and group B were 14.0 months and 4.0 months respectively. The difference of the two groups was significantly (χ2=11.728, P<0.01). There was no severe side-effect related to therapy in both groups. Conclusion: Comparing with the control group, TACE combined with percutaneous injection of chemoembolization agent intra-portal vein tumor thrombosis could significantly prolong the median survival time of

  9. Factors affecting intrapatient liver and mediastinal blood pool 18F-FDG standardized uptake value changes during ABVD chemotherapy in Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    The aim of our study was to assess the intrapatient variability of 2-deoxy-2-(18F)-fluoro-D-glucose (18F-FDG) uptake in the liver and in the mediastinum among patients with Hodgkin's lymphoma (HL) treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (CHT). The study included 68 patients (30 men, 38 women; mean age 32 ± 11 years) with biopsy-proven HL. According to Ann Arbor criteria, 6 were stage I, 34 were stage II, 12 were stage 3 and 16 were stage 4. All of them underwent a baseline (PET0) and an interim (PET2) 18F-FDG whole-body positron emission tomography (PET)/CT. All patients were treated after PET0 with two ABVD cycles for 2 months that ended 15 ± 5 days prior to the PET2 examination. All patients were further evaluated 15 ± 6 days after four additional ABVD cycles (PET6). None of the patients presented a serum glucose level higher than 107 mg/dl. The mean and maximum standardized uptake values (SUV) of the liver and mediastinum were calculated using the same standard protocol for PET0, PET2 and PET6, respectively. Data were examined by means of the Wilcoxon matched pairs test and linear regression analysis. The main results of our study were an increased liver SUVmean in PET2 (1.76 ± 0.35) as compared with that of PET0 (1.57 ± 0.31; p max in PET2 (3.13 ± 0.67) as compared with that of PET0 (2.82 ± 0.64; p mean and SUVmax in PET0, PET2 and PET6 (p > 0.05). Another finding is a relationship in PET0 between liver SUVmean and SUVmax with the stage, which was lower in those patients with advanced disease (r2 = 0.1456 and p = 0.0013 for SUVmean and r2 = 0.1277 and p = 0.0028 for SUVmax). The results of our study suggest that liver 18F-FDG uptake is variable in patients with HL during the CHT treatment and the disease course and should be considered carefully when used to define the response to therapy in the interim PET in HL. (orig.)

  10. Down-regulation of the nuclear factor-kappaB by lidamycin in association with inducing apoptosis in human pancreatic cancer cells and inhibiting xenograft growth.

    Science.gov (United States)

    Chen, Jing; Ouyang, Zhi-Gang; Zhang, Sheng-Hua; Zhen, Yong-Su

    2007-06-01

    Pancreatic cancer is now one of the most common causes of cancer death worldwide. K-ras mutations are present in up to 90% of pancreatic cancer cases. The expression of mutant K-ras activates the Akt/protein kinase B pathway, resulting in the activation of the nuclear factor-kappaB (NF-kappaB) transcriptional factor. Constitutive NF-kappaB activity plays a key role in pancreatic carcinoma. NF-kappaB has been shown to inhibit apoptosis in response to chemotherapeutic agents. In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, were investigated on two established pancreatic cell lines, PANC-1 and SW1990. A dose-dependent inhibition of phospho-Akt and NF-kappaB activation was found in the cells treated with LDM as determined by Western blot analysis. Moreover, a down-regulation of K-ras mRNA and a protein expression by LDM were observed in both cell lines as determined by reverse transcription-PCR and Western blot analysis. By MTT assay, a remarkable difference in chemosensitivity to LDM, mitomycin, adriamycin, taxol, and gemcitabine was found in both cell lines. The IC50 values of LDM for the PANC-1 or SW1990 cells were 0.955+/-0.414 or 0.426+/-0.212 nM, respectively, lower than those of the other drugs. Growth inhibition, apoptosis induction and cell cycle arrest were observed in the LDM-treated cells. LDM decreased the invasive potential of pancreatic cancer cells by reducing matrix metalloproteinase-9 activity. Furthermore, LDM was found to suppress the growth of SW1990 xenografts in nude mice. Treatment with an i.v. injection of LDM at the dose of 0.02 and 0.04 mg/kg (once a week for two weeks) inhibited the growth of xenografts by 66 and 72%, respectively. By contrast, an i.p. injection of gemcitabine at the dose of 80 mg/kg inhibited the growth of xenografts by 38%. Our findings suggest that LDM is active in the down-regulation of NF-kappaB and could play a positive role in relevant targeted chemotherapy for

  11. Response to chemotherapy and association with three tumour markers in breast cancer patients in Ghana

    Directory of Open Access Journals (Sweden)

    Emmanuel Amankwaa Frempong

    2014-08-01

    Full Text Available Purpose: Oestrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor 2 (HER2/neu expression in breast cancer patients predict response to chemotherapy though recorded extent vary. This retrospective study aimed to investigate the relationship between ER, PR and HER2/neu expression and response of breast cancer to chemotherapy at a tertiary hospital in Ghana. Methods: Records of all breast cancer cases seen from 2009 through 2011 were reviewed. Their receptor status, first line treatment [4 cycles of Adriamycin (60mg/m2 + Cyclophosphamide (600mg/m2], second line treatment [Capecitabine (1g/m2 + Paclitaxel (170mg/m2] and clinical response were extracted.Results: Complete remission after first and second line treatments were observed in 36 (38.3%, 95% CI: 28.5 to 48.9 and 34 (58.6%, 95% CI: .44.9 to 71.4 respectively. After both first and second line treatment 70 (74.5%, 95% CI: 64.4 - 82.9 had gone into remission. Prevalence of ER, PR, HER2/neu and Triple negative breast cancer (TNBC were 34.0% (95% CI: 24.6 to 44.5, 20.2% (95% CI: 12.6 to 29.7, 8.5% (95% CI: 3.7 to 16.1 and 59.6% (95%CI: 48.9 to 69.6 respectively. ER and PR positivity were independently associated with complete remission after first line treatment while TNBC was associated with non-remission. Conversely ER was independently associated with non-remission after second line treatment while TNBC was associated with complete remission. Conclusion: ER and TNBC status are significant predictors of complete remission and non-remission respectively after chemotherapy for breast cancer patient in Ghana.................................................................Cite this article as:Amankwaa-Frempong E, Yeboah FA, Nguah SB, Afriyie OO. Response to chemotherapy and association with three tumour markers in breast cancer patients in Ghana. Int J Cancer Ther Oncol 2014; 2(3:02034. DOI: 10.14319/ijcto.0203.4

  12. The hypoxia-mimetic agent CoCl2 induces chemotherapy resistance in LOVO colorectal cancer cells.

    Science.gov (United States)

    Yang, Guanglei; Xu, Shuqing; Peng, Lintao; Li, Hui; Zhao, Yan; Hu, Yanfang

    2016-03-01

    Hypoxia, which is an important factor that mediates tumor progression and poor treatment response, is particularly associated with tumor chemoresistance. However, the molecular mechanisms underlying hypoxia-induced colorectal cancer chemoresistance remain unclear. The present study aimed to explore the mechanism underlying hypoxia‑induced chemotherapy resistance in LOVO colorectal cancer cells. LOVO cells were cultured in a hypoxic environment simulated by cobalt chloride (CoCl2), which is a chemical inducer of hypoxia‑inducible factor‑1α (HIF‑1α). HIF‑1α is a transcription factor that has an important role in tumor cell adaptation to hypoxia, and controls the expression of several genes. Various CoCl2 concentrations are often used to simulate degrees of hypoxia. In the present study, following treatment with CoCl2, an MTT assay was conducted to determine the growth and drug sensitivity of LOVO cells. Reverse transcription‑polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of HIF‑1α and factors associated with chemotherapy resistance, including multidrug resistance protein (MRP) and multidrug resistant 1 (MDR1), which encodes the major transmembrane efflux transporter P‑glycoprotein (P‑gp). In addition, the expression levels of apoptosis‑related proteins, including B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and Bcl‑2‑associated agonist of cell death (Bad) were detected by western blotting. Flow cytometry (FCM) was used to visually observe Adriamycin (ADR) accumulation and retention, thus analyzing intracellular drug transportation in cells under hypoxic and normoxic conditions. CoCl2‑simulated hypoxia was able to inhibit tumor cell proliferation, and upregulate the expression levels of HIF‑1α, MDR1/P‑gp and MRP. In addition, proapoptotic members of the Bcl‑2 protein family, Bax and Bad, were downregulated. The anti‑apoptotic member Bcl‑2

  13. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

    International Nuclear Information System (INIS)

    Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient

  14. Interim PET After Two ABVD Cycles in Early-Stage Hodgkin Lymphoma: Outcomes Following the Continuation of Chemotherapy Plus Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Simontacchi, Gabriele [Radiotherapy Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence (Italy); Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, University of Torino, Torino (Italy); Ciammella, Patrizia [Radiation Oncology Unit, Department of Advanced Technology, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (Italy); Buglione, Michela [Radiation Oncology Department, University and Spedali Civili, Brescia (Italy); Saieva, Calogero [Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence (Italy); Magrini, Stefano Maria [Radiation Oncology Department, University and Spedali Civili, Brescia (Italy); Livi, Lorenzo [Radiotherapy Unit, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence (Italy); Iotti, Cinzia [Radiation Oncology Unit, Department of Advanced Technology, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (Italy); Botto, Barbara [Hematology Unit, Città della Salute e della Scienza Hospital, Torino (Italy); Vaggelli, Luca [Nuclear Medicine Department, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence (Italy); Re, Alessandro [Hematology Unit, University and Spedali Civili, Brescia (Italy); Merli, Francesco [Hematology Unit, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia (Italy); Ricardi, Umberto [Department of Oncology, University of Torino, Torino (Italy)

    2015-08-01

    Purpose: This multicenter retrospective study was designed to evaluate the prognostic role of interim fluorodeoxyglucose-labeled positron emission tomography (i-FDG-PET) in a cohort of patients affected with early-stage Hodgkin lymphoma (HL) treated initially with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by radiation therapy, and to assess the role of chemotherapy continuation plus radiation therapy for i-FDG-PET-positive patients. Methods and Materials: Data from 257 patients were retrieved from 4 hematology and radiation oncology departments. Inclusion criteria were stage I to IIAB HL, “intention-to-treat” AVBD plus radiation therapy, and FDG-PET at diagnosis and after the first 2 ABVD cycles. All i-FDG-PET scans underwent blinded local review by using the Deauville 5-point scoring system; patients were stratified as negative or positive using 2 Deauville score cutoff values, ≥3 or ≥4. Results: Median follow-up time was 56 months (range: 9-163 months); 5-year overall survival (OS) and disease-specific survival (DSS) for the whole cohort were 97.5% and 98.3%, respectively. Five-year progression-free survival (PFS) was 95.6%. After i-FDG-PET revision, 43 of 257 patients (16.7%) had a positive i-FDG-PET (Deauville scores: 3-5). Five-year PFS rates for i-FDG-PET-negative and i-FDG-PET-positive patients were 98.1% and 83.7%, respectively, if using a Deauville score cutoff of 3, and 97.7% and 78.6%, respectively, if using a cutoff of 4 (P=.0001). Five-year OS for i-FDG-PET-negative and i-FDG-PET-positive patients was 98.5% and 93.0%, respectively, if using a cutoff of 3, and 98.6% and 89.3%, respectively, if using a cutoff of 4 (P=.029 and P=.002). At univariate regression analysis, i-FDG-PET positivity was associated with worse OS and PFS. At multivariate analysis, performed only for PFS, i-FDG-PET positivity confirmed its negative impact (P=.002). Conclusions: i-FDG-PET is prognostic for PFS and OS in early-stage HL

  15. The 2013 SFRBM discovery award: selected discoveries from the butterfield laboratory of oxidative stress and its sequela in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment.

    Science.gov (United States)

    Butterfield, D Allan

    2014-09-01

    This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy-induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called "chemobrain" by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a proinflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent with

  16. The role of mitoxantrone in the treatment of indolent lymphomas.

    Science.gov (United States)

    Hagemeister, Fredrick; Cabanillas, Fernando; Coleman, Morton; Gregory, Stephanie A; Zinzani, Pier Luigi

    2005-02-01

    With the introduction of newer therapeutic approaches, survival in indolent non-Hodgkin's lymphoma (NHL) appears to be improving. Mitoxantrone (Novantrone; Serono, Inc.; Rockland, MA, http://www.seronousa.com), an anthracenedione with low cardiotoxic potential, has demonstrated activity in indolent NHL in combination with fludarabine (Fludara; Berlex Laboratories; Wayne, NJ, http://www.berlex.com) and other agents. In a Southwest Oncology Group trial (SWOG 9501), treatment with fludarabine and mitoxantrone (FM) induced a complete remission (CR) rate of 44% and a partial remission (PR) rate of 50% in untreated patients. The estimated 4-year progression-free survival (PFS) rate was 38%. In a multicenter Italian trial comparing the efficacy of FM with that of cyclophosphamide, doxorubicin (Adriamycin; Bedford Laboratories; Bedford, OH, http://www.bedfordlabs.com), vincristine (Oncovin; Eli Lilly and Company; Indianapolis, IN, http://www.lilly.com), and prednisone (Deltasone; Pfizer Pharmaceuticals; New York, NY, http://www.pfizer.com), CHOP, followed by rituximab (Rituxan; Genentech, Inc.; South San Francisco, CA, http://www.gene.com) for patients with incomplete clinical or molecular responses, the CR and molecular response rates were significantly higher in the FM arm, but the PFS and overall survival (OS) rates did not differ between the two arms. However, FM was also significantly less toxic than CHOP. The administration of rituximab following chemotherapy resulted in higher clinical and molecular response rates in both arms. In a separate trial, FM plus dexamethasone (Decadron; Merck and Co., Inc.; Whitehouse Station, NJ, http://www.merck.com), FND, plus concurrent rituximab produced a CR rate of 92%. In a randomized German study, patients with indolent lymphomas received FM plus cyclophosphamide (FCM) or FCM with rituximab. PFS and OS times were significantly better for patients who received combined chemoimmunotherapy. Mitoxantrone-based regimens are highly

  17. Twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung Gu; Cho, Moon June; Kim, Sun Young; Kim, Ki Whan; Kim, Jun Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2006-06-15

    A retrospective study was performed to evaluate the efficiency and feasibility of twice daily radiation therapy plus concurrent chemotherapy for limited-stage small cell lung cancer in terms of treatment response, survival, patterns of failure, and acute toxicities. Between February 1993 and October 2002, 76 patients of histologically proven limited-stage small cell lung cancer (LS-SCLC) were treated with twice daily radiation therapy and concurrent chemotherapy. Male was in 84% (64/76), and median age was 57 years (range, 32 {approx} 75 years). Thoracic radiation therapy consisted of 120 or 150 cGy per fraction, twice a day at least 6 hours apart, 5 days a week. Median total dose was 50.4 Gy (range, 45 {approx} 51 Gy). Concurrent chemotherapy consisted of CAV (cytoxan 1000 mg/m{sup 2}, adriamycin 40 mg/m{sup 2}, vincristine 1 mg/m{sup 2}) alternating with PE (cisplatin 60 mg/m{sup 2}, etoposide 100 mg/m{sup 2}) or PE alone, every 3 weeks. The median cycle of chemotherapy was six (range, 1 {approx} 9 cycle). Prophylactic cranial irradiation (PCI) was recommended to the patients who achieved a complete response (CR). PCI scheme was 25 Gy/ 10 fractions. Median follow up was 18 months (range, 1 {approx} 136 months). Overall response rate was 86%; complete response in 39 (52%) and partial response in 26 (34%) patients. The median overall survival was 23 months. One, two, and three year overall survival rate was 72%, 50% and 30%, respectively. In univariate analysis, the treatment response was revealed as a significant favorable prognostic factor for survival ({rho} < 0.001). Grade 3 or worse acute toxicities were leukopenia in 46 (61%), anemia in 5 (6%), thrombocytopenia in 10 (13%), esophagitis in 5 (6%), and pulmonary toxicity in 2 (2%) patients. Of 73 evaluable patients, 40 (55%) patients subsequently had disease progression. The most frequent first site of distant metastasis was brain. Twice daily radiation therapy plus concurrent chemotherapy produced favorable

  18. Alternating chemotherapy and hyperfractionated accelerated radiotherapy in non-metastatic inflammatory breast cancer; Radiotherapie hyperfractionnee acceleree alternee avec une chimiotherapie dans le cancer du sein inflammatoire non metastatique

    Energy Technology Data Exchange (ETDEWEB)

    Hasbini, A.; Le Pechoux, C.; Roche, B.; Pignol, J.P.; Abdulkarim, B.; Habrand, J.L. [Institut Gustave Roussy, Dept. de Radiotherapie, 94 - Villejuif (France); Zelek, L.; Spielmann, M. [Institut Gustave Roussy, Dept. d' oncologie Medicale, 94 - Villejuif (France); Arriagada, R. [Instituto de Radiomedicina, IRAM, Santiago, (Chile); Guinebretiere, J.M. [Institut Gustave Roussy, Dept. d' Anatomopothologie, 94 - Villejuif (France); Tardivon, A. [Institut Gustave Roussy, Dept. de Radiodiagnostic, 94 - Villejuif (France)

    2000-08-01

    Based on encouraging results reported in alternating radiotherapy and chemotherapy in inflammatory breast carcinoma, we have tried in this study to optimize locoregional treatment with a hyperfractionated accelerated radiotherapy schedule alternating with chemotherapy. From May 1991 to May 1995, 54 patients, previously untreated, with non-metastatic inflammatory breast cancer were entered in an alternating protocol consisting of eight courses of combined chemotherapy and two series of loco-regional hyperfractionated accelerated radiotherapy with a total dose of 66 Gy. Hyperfractionated accelerated radiotherapy was started after three courses of neo-adjuvant chemotherapy (Adriamycin, Vincristine, Cyclophosphamide, Methotrexate, 5-fluoro-uracil) administered every 21 days {+-}G.CSF. The first series delivered 45 Gy/three weeks to the breast, the axillary, sub-clavicular and internal mammary nodes, with two daily sessions of 1.5 Gy separated by an interval of eight hours, the second series consisted of a boost (21 Gy/14 fractions/10d) alternating with another regimen of anthracycline-based-chemotherapy (a total of five cycles every three weeks). Hormonal treatment was given to all patients. Of the 53 patients evaluated at the end of the treatment, 44(83%) had a complete clinical response, seven (13%) had a partial response (>50%) and two (4%) had tumoral progression. Of the 51 patients who were locally controlled, 18 (35%) presented a locoregional recurrence (LRR); eight(15 %) had to undergo a mastectomy. All the patients but two LRR developed metastases or died of local progressive disease and 26 (50%) developed metastases. With a median follow-up of 39 months (range: 4-74 months), survival rates at three and five years were respectively, 66 and 45% for overall survival and 45 and 36% for disease-free survival. Alternating a combination of chemotherapy and hyperfractionated accelerated radiotherapy is a well-tolerated regimen which provides acceptable local control

  19. Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. Methods and Materials: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. Results: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). Conclusions: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete

  20. Involved-Node Radiotherapy and Modern Radiation Treatment Techniques in Patients With Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Purpose: To assess the clinical outcome of the involved-node radiotherapy (INRT) concept using modern radiation treatments (intensity-modulated radiotherapy [IMRT] or deep-inspiration breath-hold radiotherapy [DIBH) in patients with localized supradiaphragmatic Hodgkin lymphoma. Methods and Materials: All but 2 patients had early-stage Hodgkin lymphoma, and they were treated with chemotherapy prior to irradiation. Radiation treatments were delivered using the INRT concept according to European Organization for Research and Treatment of Cancer guidelines. IMRT was performed with the patient free-breathing. For the adapted breath-hold technique, a spirometer dedicated to DIBH radiotherapy was used. Three-dimensional conformal radiotherapy was performed with those patients. Results: Fifty patients with Hodgkin lymphoma (48 patients with primary Hodgkin lymphoma, 1 patient with recurrent disease, and 1 patient with refractory disease) entered the study from January 2003 to August 2008. Thirty-two patients were treated with IMRT, and 18 patients were treated with the DIBH technique. The median age was 28 years (range, 17-62 years). Thirty-four (68%) patients had stage I - (I-IIA) IIA disease, and 16 (32%) patients had stage I - (I-IIB) IIB disease. All but 3 patients received three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). The median radiation doses to patients treated with IMRT and DIBH were, respectively, 40 Gy (range, 21.6-40 Gy) and 30.6 Gy (range, 19.8-40 Gy). Protection of various organs at risk was satisfactory. Median follow-up was 53.4 months (range, 19.1-93 months). The 5-year progression-free and overall survival rates for the whole population were 92% (95% confidence interval [CI], 80%-97%) and 94% (95% CI, 75%-98%), respectively. Recurrences occurred in 4 patients: 2 patients had in-field relapses, and 2 patients had visceral recurrences. Grade 3 acute lung toxicity (transient pneumonitis) occurred in 1 case. Conclusions

  1. 同种肾组织移植治疗慢性肾功能衰竭性贫血的实验研究%Experimental study on aliograft of kidney tissue mass to treat renal anemia caused by chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    詹炳炎; 宋力; 章重; 郝平和; 金化民; 张斌; 吴天鹏; 唐进久; 徐颖; 恽金瑞; 贺衍龙

    1997-01-01

    以Wistar雄性大鼠为受体,建立慢性肾功能衰竭动物模型,将鼠婴肾组织块多点植入受体双侧后肢皮下和筋膜下.结果表明,30天后移植物的体积由lmm3增至4mm3大小,表面血管网丰富;光镜下见肾小球、肾小管结构正常.促红细胞生成素(EPO)着色颗粒主要分布在肾小球区,移植组着色程度明显增高.血红蛋白和促红细胞生成素随移植的时间延长而逐渐升高,实验结果提示,此方法有可能为治疗慢性肾功能衰竭性贫血提供一种新途径.%After the models of chronic renal failue(CRF)induced by adriamycin were set up in Wistar rats,the kidney tissue mass(1mm3)of newborn Wistar rats were located under the adrema of double legs of the models.The results were shown as follows:1)The grafts survived and were increased in size from lmm3 to 4mm3 in the period of 30 days.around which there were plenty of newborn blood vessels.Histological examination showed that the grafts had normal structure of glomerule and uriniferous tubules;2)Immunohistochemical study demonstrated Epo positive grains were located in the region of glomerule and there were more positive grains in renal tissue of the graft than that of CRF(P0.05).From the above,it was concluded that allograft transplantation of kidney mass might be a new therapeutic means to treat CRF induced anaemia.

  2. Interim PET After Two ABVD Cycles in Early-Stage Hodgkin Lymphoma: Outcomes Following the Continuation of Chemotherapy Plus Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: This multicenter retrospective study was designed to evaluate the prognostic role of interim fluorodeoxyglucose-labeled positron emission tomography (i-FDG-PET) in a cohort of patients affected with early-stage Hodgkin lymphoma (HL) treated initially with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by radiation therapy, and to assess the role of chemotherapy continuation plus radiation therapy for i-FDG-PET-positive patients. Methods and Materials: Data from 257 patients were retrieved from 4 hematology and radiation oncology departments. Inclusion criteria were stage I to IIAB HL, “intention-to-treat” AVBD plus radiation therapy, and FDG-PET at diagnosis and after the first 2 ABVD cycles. All i-FDG-PET scans underwent blinded local review by using the Deauville 5-point scoring system; patients were stratified as negative or positive using 2 Deauville score cutoff values, ≥3 or ≥4. Results: Median follow-up time was 56 months (range: 9-163 months); 5-year overall survival (OS) and disease-specific survival (DSS) for the whole cohort were 97.5% and 98.3%, respectively. Five-year progression-free survival (PFS) was 95.6%. After i-FDG-PET revision, 43 of 257 patients (16.7%) had a positive i-FDG-PET (Deauville scores: 3-5). Five-year PFS rates for i-FDG-PET-negative and i-FDG-PET-positive patients were 98.1% and 83.7%, respectively, if using a Deauville score cutoff of 3, and 97.7% and 78.6%, respectively, if using a cutoff of 4 (P=.0001). Five-year OS for i-FDG-PET-negative and i-FDG-PET-positive patients was 98.5% and 93.0%, respectively, if using a cutoff of 3, and 98.6% and 89.3%, respectively, if using a cutoff of 4 (P=.029 and P=.002). At univariate regression analysis, i-FDG-PET positivity was associated with worse OS and PFS. At multivariate analysis, performed only for PFS, i-FDG-PET positivity confirmed its negative impact (P=.002). Conclusions: i-FDG-PET is prognostic for PFS and OS in early-stage HL

  3. Preoperative Transcatheter Selective Arterial Chemoembolization in Treatment of Unresectable Hepatoblastoma in Infants and Children

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the clinical feasibility and efficacy of transcatheter selective arterial chemoembolization (TACE) for unresectable hepatoblastoma in infants and children. The study was performed with the approval of our institutional review board. Sixteen patients (13 boys, 3 girls) with unresectable hepatoblastoma were treated one to three times with preoperative TACE in an effort to improve the surgical and clinical outcome. Their ages ranged from 50 days to 60 months, with a mean age of 20.4 months. All cases were pathologically proved hepatoblastoma by fine-needle biopsy. After an intra-arterial catheter was selectively inserted into the main feeding artery of the tumor, cycles of cisplatin (40 to 50 mg/m2) and adriamycin (20 to 30 mg/m2) mixed with lipiodol were given, followed by gelatin foam particles or stainless-steel coils. Tumor response was evaluated according to tumor shrinkage, α-fetoprotein (AFP) levels, and pathological findings. TACE procedure was performed one to three times, depending on the patient's response. Surgical resection was carried out when the tumor volume appeared sufficiently reduced to allow safe resection by either lobectomy or extended lobectomy. A marked reduction in tumor size associated with decreased AFP level occurred after treatment. According to paired-samples test, tumor shrinkage ranged from 19.0% to 82.0%, with a mean value of 59.2%. AFP levels decreased 99.0% to 29.0% from initial levels, with a mean decrease of 60.0%. TACE allowed subsequent complete surgical resection in 13 cases and the other 3 cases underwent partial resection. One patient underwent successful orthotopic liver transplantation after receiving TACE therapy. Pathological examination showed that the mean percentage of necrotic area in the surgical specimens was 87%. Overall survival rate at 1, 3, and 5 years was 87.5%, 68.7%, and 50%, respectively. Correspondingly, event-free survival rate was 75%, 62.5%, and 43

  4. The Reversal Effect and Its Mechanisms of Tetramethylpyrazine on Multidrug Resistance in Human Bladder Cancer

    Science.gov (United States)

    Wang, Shanshan; Lei, Ting; Zhang, Man

    2016-01-01

    Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR). To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (-)-Epigallocatechin gallate (EGCG) and Tetramethylpyrazine (TMP) to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM)-resistant Pumc-91 cells (Pumc-91/ADM) were assessed by Cell Counting Kit-8 (CCK-8) cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc-91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer chemotherapy. PMID

  5. Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, University of Torino, Torino (Italy); Ciammella, Patrizia [Radiation Therapy Unit, Department of Oncology and Advanced Technology, ASMN Hospital IRCCS, Reggio Emilia (Italy); Piva, Cristina; Ragona, Riccardo [Department of Oncology, University of Torino, Torino (Italy); Botto, Barbara [Hematology, Città della Salute e della Scienza, Torino (Italy); Gavarotti, Paolo [Hematology, University of Torino and Città della Salute e della Scienza, Torino (Italy); Merli, Francesco [Hematology Unit, ASMN Hospital IRCCS, Reggio Emilia (Italy); Vitolo, Umberto [Hematology, Città della Salute e della Scienza, Torino (Italy); Iotti, Cinzia [Radiation Therapy Unit, Department of Oncology and Advanced Technology, ASMN Hospital IRCCS, Reggio Emilia (Italy); Ricardi, Umberto [Department of Oncology, University of Torino, Torino (Italy)

    2014-06-01

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. Methods and Materials: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. Results: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). Conclusions: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete

  6. Mutation in mitochondrial complex I ND6 subunit is associated with defective response to hypoxia in human glioma cells

    Directory of Open Access Journals (Sweden)

    Salloum Nicole

    2004-07-01

    Full Text Available Abstract Background Hypoxia-tolerant human glioma cells reduce oxygen consumption rate in response to oxygen deficit, a defense mechanism that contributes to survival under moderately hypoxic conditions. In contrast, hypoxia-sensitive cells lack this ability. As it has been previously shown that hypoxia-tolerant (M006x, M006xLo, M059K and -sensitive (M010b glioma cells express differences in mitochondrial function, we investigated whether mitochondrial DNA-encoded mutations are associated with differences in the initial response to oxygen deficit. Results The mitochondrial genome was sequenced and 23 mtDNA alterations were identified, one of which was an unreported mutation (T-C transition in base pair 14634 in the hypoxia-sensitive cell line, M010b, that resulted in a single amino acid change in the gene encoding the ND6 subunit of NADH:ubiquinone oxidoreductase (Complex I. The T14634C mutation did not abrogate ND6 protein expression, however, M010b cells were more resistant to rotenone, an agent used to screen for Complex I mutations, and adriamycin, an agent activated by redox cycling. The specific function of mtDNA-encoded, membrane-embedded Complex I ND subunits is not known at present. Current models suggest that the transmembrane arm of Complex I may serve as a conformationally driven proton channel. As cellular respiration is regulated, in part, by proton flux, we used homology-based modeling and computational molecular biology to predict the 3D structure of the wild type and mutated ND6 proteins. These models predict that the T14634C mutation alters the structure and orientation of the trans-membrane helices of the ND6 protein. Conclusion Complex I ND subunits are mutational hot spots in tumor mtDNA. Genetic changes that alter Complex I structure and function may alter a cell's ability to respond to oxygen deficit and consolidate hypoxia rescue mechanisms, and may contribute to resistance to chemotherapeutic agents that require redox

  7. Reversion effects of curcumin on multidrug resistance of MNNG/HOS human osteosarcoma cells in vitro and in vivo through regulation of P-glycoprotein

    Institute of Scientific and Technical Information of China (English)

    SI Meng; ZHAO Jie; LI Xin; TIAN Ji-guang; LI Yong-gang; LI Jian-min

    2013-01-01

    Background P-glycoprotein (P-gp) encoded by ATP-binding cassette sub-family B member 1 (ABCB1) gene is a kind of ATP-dependent drug transporter,which plays important roles in multidrug resistance (MDR) of human cancers,such as osteosarcoma.Curcumin is a natural phenolic coloring compound originating from the rhizomes of Curcuma longa,which is proved to possess antitumor biological activities including reversion of MDR.However,the effect and molecular mechanisms of curcumin to osteosarcoma MDR remain unclear.Methods We established a human osteosarcoma drug-resistant cell line MNNG/HOS/MTX by pulse exposure to methotrexate (MTX) and verified that the new cell lines were cross-resistant to other anticancer agents.Then,according to the cytotoxicity assay,we reversed MDR of MNNG/HOS/MTX by 30 μmol/L curcumin,and detected the mechanisms of curcumin reversing MDR through Real-time PCR,Western blotting assay,and Rhodamine123 (Rh123)transport test.Finally,we evaluated the effect of curcumin reversing MDR in vivo by MNNG/HOS/MTX cells xenograft-nude mice model.Results MNNG/HOS/MTX was proved to be a human osteosarcoma MDR cell line.MTT tumor chemosensitivity test indicates that 30 μmol/L curcumin attenuates the half maximal inhibitory concentration (IC50) and resistance index (RI)to MTX,diamminedichloroplatinum (DDP),adriamycin (ADM),ifosfamide (IFO),and epirubicin (EPI) in MNNG/HOS/MTX cells (P <0.05).Real-time PCR and Western blotting assays demonstrated that curcumin down-regulated P-gp expression of MNNG/HOS/MTX cells.Rh123 transport test showed that curcumin inhibited the transport function of P-gp in vitro.In vivo studies showed that curcumin displayed the features of sensitizing antitumor drugs and inhibiting the proliferation,invasion,and metastasis of osteosarcoma MDR cells.Conclusion Down-regulation of P-gp and inhibition of the function of P-gp efflux pump may contribute to MDR reversion induced by curcumin in vitro and in vivo.

  8. The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Dong S

    2013-10-01

    Full Text Available Shengli Dong,1 Qibin Tang,2 Miaoyun Long,3 Jian Guan,4 Lu Ye,5 Gaopeng Li6 1Department of General Surgery, The Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi Province, 2Department of Hepatobiliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 3Department of Thyroid and Vascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 4Department of Radiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 5Infection Department, Guangzhou No 8 Hospital, Guangzhou, Guangdong Province, 6Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China Background/aim: A local nanotherapy (LNT combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT. Methods: In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM, mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting

  9. Establishment of a P-glycoprotein substrate screening model and its preliminary application

    Institute of Scientific and Technical Information of China (English)

    Yi Wang; Jiang Cao; Su Zeng

    2004-01-01

    AIM: To establish a high P-glycoprotein (P-gp) expressing cell line as a model for studying drug absorption and distribution, and to explore the preliminary application of this screening model.METHODS: A full-length MDR1 cDNA fragment in plasmid pMDRA1 was first subcloned into plasmid pET28a(+), then MDR1 cDNA was cut from the recombinant plasmid with double-digestion and ligated into the mammalian expression vector pcDNA3.1(+). The recombinant plasmid pcDNA3.1(+)/MDR1 was transfected into breast cancer cell line Bcap37using the Superfect transfection reagent. Several stably transfected clones were obtained after selection with G418.Real-time fluorescent quantitative RT- PCR and Western blot methods were used to detect the expression of P-gp, and the cellular location of the expressed protein was determined by immunohistochemical staining. Drug sensitivity assay was used to evaluate the biological function of expressed P-gp.Concentration of quercetin in cells was determined by highperformance liquid chromatography (HPLC).RESULTS: The recombinant plasmid was confirmed to be inserted in the correct orientation by restrictive enzyme digestion and DNA sequencing. Real-time fluorescent quantitative RT-PCR showed a higher level of P-cp mRNA in transfected cells compared to that in the control cells, and the Western blot result also indicated that P-gp expression in transfected cells was higher than that in control cells. The immunohistochemical staining showed that the expressed P-gp was localized on cell membranes. Drug sensitivity assay showed that the IC50 for adriamycin and colchicine of the transfected cells was higher than that of the control cells.The concentration of quercetin in model cells was lower than that in control cells by HPLC. After P-gp inhibitor verapamil was administered, the concentration of quercetin in model cells was increased.CONCLUSION: A high P-gp expressing ceil line can be established, which could provide a suitable in vitro model system for

  10. Electronic structure and partial charge distribution of doxorubicin under different molecular environments

    Science.gov (United States)

    Poudel, Lokendra

    Doxorubicin (trade name Adriamycin, abbreviated DOX) is a well-known an- thracyclic chemotherapeutic used in treating a variety of cancers including acute leukemia, lymphoma, multiple myeloma, and a range of stomach, lung, bladder, bone, breast, and ovarian cancers. The purpose of the present work is to study electronic structure, partial charge distribution and interaction energy of DOX under different environments. It provides a framework for better understanding of bioactivity of DOX with DNA. While in this work, we focus on DOX -- DNA interactions; the obtained knowledge could be translated to other drug -- target interactions or biomolecular interactions. The electronic structure and partial charge distribution of DOX in three dierent molecular environments: isolated, solvated, and intercalated into a DNA complex,were studied by rst principles density functional methods. It is shown that the addition of solvating water molecules to DOX and the proximity and interaction with DNA has a signicant impact on the electronic structure as well as the partial charge distribution. The calculated total partial charges for DOX in the three models are 0.0, +0.123 and -0.06 electrons for the isolated, solvated, and intercalated state, respectively. Furthermore, by using the more accurate ab initio partial charge values on every atom in the models, signicant improvement in estimating the DOX-DNA interaction energy is obtained in conjunction with the NAnoscale Molecular Dynamics (NAMD) code. The electronic structure of the DOX-DNA is further elucidated by resolving the total density of states (TDOS) into dierent functional groups of DOX, DNA, water, co-crystallized Spermine molecule, and Na ions. The surface partial charge distribution in the DOX-DNA is calculated and displayed graphically. We conclude that the presence of the solvent as well as the details of the interaction geometry matter greatly in the determination of the stability of the DOX complexion. Ab initio

  11. Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: a single institution experience

    International Nuclear Information System (INIS)

    Because of need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSHRC) and King Fahd National Center for Children's Cancer and Research (KFNCCCR) over a period of 18 years with a focus on patient characteristics and outcome. During the period of 1981 to 1988, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90) and subsequently. Children's Cancer Group (CCG) protocols and these were grouped as Era (1981-1992) and Era 2 (1993-1998). Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotexate (MTX) 1g/m2 and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 cyclophosphamide .International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs using the post-remission period. The end of induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=0.49). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P<.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important

  12. Therapeutic Effect Evaluation of the Combination Regimen of Rituximab and CHOP for CD20 Positive Diffuse Large B-cell Lymphoma%R-CHOP方案初治CD20阳性弥漫大B细胞淋巴瘤的临床疗效评价

    Institute of Scientific and Technical Information of China (English)

    刘爱学; 张容榕; 李明淑; 周泽强; 冯天举

    2012-01-01

    目的:观察利妥昔单抗联合CHOP方案(R-CHOP方案)初治弥漫大B细胞淋巴瘤的疗效及不良反应.方法:对20例初治弥漫大B细胞淋巴瘤患者,给予6周期~8周期R-CHOP方案治疗.利妥昔单抗375mg/m2,静滴,d1;环磷酰胺750mg/m2,iv,d1;阿霉素50mg/m2,iv,d1;长春新碱1.4mg/m2,iv,d1;强的松100mg/d,口服,d1-5;21天为一周期.结果:20例患者中,完全缓解13例,部分缓解3例,稳定1例,进展3例,客观缓解率80%.主要毒副反应为血液学毒性,轻度胃肠道反应,无利妥昔单抗不良反应.结论:R-CHOP方案初治CD20阳性弥漫大B细胞淋巴瘤缓解率高,毒副反应可以耐受.%Objective: To observe the effect and toxicity of combination treatment of rituximab and CHOP-regimen for diffuse large B cell lymphoma( DLBCL ). Methods: 20 patients initially diagnosed as DLBCL received R-CHOP regimen of 6 - 8 cycles: rituximab 375mg/m intravenously infused on dayl, cyclophosphamide 750mg/m on clayl, adriamycin 50mg/m2 on clayl and vincristine 1. 4mg/m on day 1, prednisone lOOmg/d taken orally on day 1 ~5; 21days as one cycle. Results: In all 20 patients, 13 got complete response and 3 partial response, 1 SD, 3 PD. The overall response rate was 80. 0%. Main toxicity included myelosuppression, slightly gastrointestinal reaction. No rituximab related toxicity was observed in all the patients. Conclusion: R-CHOP regimen has high efficacy with mild toxicity in the treatment of initially diagnosed diffuse large B cell lymphoma.

  13. REVERSAL EFFECTS OF MIFEPRISTONE ON MULTIDRUG RESISTANCE(MDR) IN DRUG-RESISTANT BREAST CANCER CELL LINE MCF7/ADR IN VITRO AND IN VIVO

    Institute of Scientific and Technical Information of China (English)

    李大强; 潘丽华; 邵志敏

    2004-01-01

    Objective: To explore the reversal effect of mifepristone on multidrug resistance (MDR) in drug-resistant human breast cancer cell line MCF7/ADR and its mechanisms. Methods: Expression of MDR1 and MDR-associated protein(MRP) mRNA in MCF7/ADR cells was detected using reverse transcription- polymerase chain reaction(RT-PCR). Western blotting was used to assay the protein levels of P-glycoprotein (P-gp) and MRP. Intracellular rhodamine 123 retention and [3H]vincristine (VCR) accumulation were measured by flow cytometry and liquid scintillation counter, respectively. MTT reduction assay was used to determine the sensitivity of cells to the anticancer agent, adriamycin (ADR). Additionally, a MCF7/ADR cell xenograft model was established to assess the reversal effect of mifeprisone on MDR in MCF7/ADR cells in vivo. Results: Miferpristone dose-dependently down- regulated the expression of MDR1 and MRP mRNA in MCF7/ADR cells, accompanied by a significant decrease in the protein levels of P-gp and MRP. After exposure to 5, 10, and 20 μmol/L mifepristone, MCF7/ADR cells showed a 3.87-, 5.81-, and 7.40-fold increase in the accumulation of intracellular VCR(a known substrate of MRP), and a 2.14-, 4.39-, and 5.53-fold increase in the retention of intracellular rhodamine 123(an indicator of P-gp function), respectively. MTT analysis showed that the sensitivity of MCF7/ADR cells to ADR was enhanced by 7.23-, 13.62-, and 20.96-fold after incubation with mifepristone as above-mentioned doses for 96 h. In vivo, mifepristone effectively restored the chemosensitivity of MCF7/ADR cells to ADR. After 8 weeks of administration with ADR(2 mg·kg-1·d-1) alone or in combination with mifepristone(50 mg·kg-1·d-1), the growth inhibitory rate of xenografted tumors in nude mice was 8.08% and 37.25%, respectively. Conclusion: Mifepristone exerts potent reversal effects on MDR in MCF7/ADR cells in vitro and in vivo through down- regulation of MDR1/P-gp and MRP expression and inhibition of P

  14. Functional study of the novel multidrug resistance gene HA117 and its comparison to multidrug resistance gene 1

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    Chen Tingfu

    2010-07-01

    Full Text Available Abstract Background The novel gene HA117 is a multidrug resistance (MDR gene expressed by all-trans retinoic acid-resistant HL-60 cells. In the present study, we compared the multidrug resistance of the HA117 with that of the classical multidrug resistance gene 1 (MDR1 in breast cancer cell line 4T1. Methods Transduction of the breast cancer cell line 4T1 with adenoviral vectors encoding the HA117 gene and the green fluorescence protein gene (GFP (Ad-GFP-HA117, the MDR1 and GFP (Ad-GFP-MDR1 or GFP (Ad-GFP was respectively carried out. The transduction efficiency and the multiplicity of infection (MOI were detected by fluorescence microscope and flow cytometry. The transcription of HA117 gene and MDR1 gene were detected by reverse transcription polymerase chain reaction (RT-PCR. Western blotting analysis was used to detect the expression of P-glycoprotein (P-gp but the expression of HA117 could not be analyzed as it is a novel gene and its antibody has not yet been synthesized. The drug-excretion activity of HA117 and MDR1 were determined by daunorubicin (DNR efflux assay. The drug sensitivities of 4T1/HA117 and 4T1/MDR1 to chemotherapeutic agents were detected by Methyl-Thiazolyl-Tetrazolium (MTT assay. Results The transducted efficiency of Ad-GFP-HA117 and Ad-GFP-MDR1 were 75%-80% when MOI was equal to 50. The transduction of Ad-GFP-HA117 and Ad-GFP-MDR1 could increase the expression of HA117 and MDR1. The drug resistance index to Adriamycin (ADM, vincristine (VCR, paclitaxel (Taxol and bleomycin (BLM increased to19.8050, 9.0663, 9.7245, 3.5650 respectively for 4T1/HA117 and 24.2236, 11.0480, 11.3741, 0.9630 respectively for 4T1/MDR1 as compared to the control cells. There were no significant differences in drug sensitivity between 4T1/HA117 and 4T1/MDR1 for the P-gp substrates (ADM, VCR and Taxol (P Conclusions These results confirm that HA117 is a strong MDR gene in both HL-60 and 4T1 cells. Furthermore, our results indicate that the MDR

  15. Use of conventional radiopharmaceuticals in drug development

    International Nuclear Information System (INIS)

    Full text: Non beta-plus radiopharmaceuticals are routinely used to monitor therapeutic and toxic effects of drugs but still there is hesitancy in using them in drug development mainly due to the fact that most of them cannot be used to directly assess the target site for which the drug is being developed. However, they can be useful during safety, preclinical and clinical testing of new drugs to measure or monitor the pharmacodynamic effects of the drug on the tissue. Initial toxic effect of the drug can be studied in small and or large animals. Screening of multiorgan toxicity can be done in small animals while chronological studies can be done in large animals where planar or SPECT imaging can be performed. For screening, a lipophilic radioactive tracer such as 125I-HIPDM can be used to study multiorgan toxicity. The percentage uptake in various organs of the drug-treated and control animals are compared to each other and the difference is assumed to reflect the tissue response of the drug. Once such a determination is made, organ-specific radiopharmaceuticals are then used to more accurately determine the toxic effect of the candidate drug as exemplified in the use of In-111 antimyosin antibody to document cardiotoxicity of the anthracyclines (particularly adriamycin). During pre-clinical and clinical testing stages, the non beta-plus radiopharmaceutical can be used to determine the therapeutic efficacy of the candidate drug as exemplified in the use of Ga-67 citrate to monitor chemotherapeutic treatment in cancer patients. The use of non-beta plus radiopharmaceuticals in drug development offers several advantages: a) the procedure is currently being routinely used to monitor therapeutic and toxic effects of drugs; b) it is simple, repeatable and adaptable to a chronological study using the same animal when employing imaging technique; c) it can be done in human thereby avoiding the necessity of extrapolating data from animals to human. To establish the use of

  16. Enhanced chemosensitivity of p73α gene transferred into H1299 cell line of human lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Yong; FAN Shi-zhi; Kalkunte S Srivenugopal; JIANG Yao-guang; QIN Chuan

    2004-01-01

    Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome;The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents ( 1.25 μmol/L of cDDP and 0.05 μmol/L of ADM)could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38.4% ( P < 0.01 ) and that of ADM from 12.1% to 49.3 % ( P < 0.01 ). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P < 0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.

  17. Efficacy, safety, and lack of interactions with the use of raltegravir in HIV-infected patients undergoing antineoplastic chemotherapy

    Directory of Open Access Journals (Sweden)

    Sara Bañón

    2014-11-01

    Full Text Available Introduction: Concomitant use of combination antiretroviral regimen (cART and cancer chemotherapy is difficult due to complex interactions and increased toxicity. Raltegravir could be an adequate option through its favourable drug-drug interaction profile. Methods: Prospective longitudinal study of HIV patients with cancer, AIDS related or not, undergoing chemotherapy. Patients without resistance or previous failure were switched or initiated raltegravir plus two nucleoside analogues. Plasma trough levels of raltegravir were measured. Results: Overall, 28 patients receiving a raltegravir-based regimen (4 naive with tenofovir-emtricitabine (18 cases or abacavir-lamivudine (10 cases were included. Mean age was 46.2 years (IQR, 39–52.7, and 79% were male. Median time of HIV was 201.7 months, CD4+ nadir was 268 cells/mm3, and 75% had previous AIDS. At the diagnosis of neoplasia, 17 were on protease inhibitors and 4 with efavirenz. Ten patients had a non-HIV-related cancer (three breast, two pancreatic, one Ewing sarcoma, one myeloblastic leukemia, one melanoma, one parotid adenocarcinoma, one lung, and 18 had an HIV-related cancer (nine non-Hodgkin lymphoma, seven Hodgkin disease, two anal. Overall, 43% of patients received more than one line of chemotherapy, including antimetabolites in 12 patients (5-FU, capecitabine, methotrexate, gemcitabine, alkylating agents in 12 cases (ciclophosphamide, iphosphamide, vinca alkaloids in 20 patients (vincristine, vinblastine, vindesine, antitumor antibiotics in 16 cases (adriamycin, cisplatin o carboplatin in six and monoclonal antibodies in six patients (rituximab, trastuzumab, cetuximab. Six patients modified the doses of antineoplastic agents due to toxicity (four neutropenia, not related to raltegravir. During a median follow up of 12.7 patients-year in concomitant therapy, there was only 1 case of virological failure and no patient discontinued raltegravir. Plasma concentrations of raltegravir in eight

  18. Cytotoxic effect of essential oil of thyme (Thymus broussonettii on the IGR-OV1 tumor cells resistant to chemotherapy

    Directory of Open Access Journals (Sweden)

    L. Ait M'Barek

    2007-11-01

    Full Text Available The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii essential oil (EOT was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR, OV1/vincristine (OV1/VCR, and OV1/cisplatin (OV1/CDDP. All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean ± SEM, v/v were 0.40 ± 0.02, 0.39 ± 0.02, 0.94 ± 0.05, and 0.65 ± 0.03% for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 ± 0.27, 1.35 ± 0.20, and 0.85 ± 0.18 cm³ after injection with 10, 30, or 50 µL per 72 h (six times, respectively, as opposed to 3.88 ± 0.50 cm³ for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 ± 4, 18 ± 4, and 8 ± 3%, respectively, while the control animals showed 75 ± 10% of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.

  19. [Comparison of protein expression profiles between bortezomib-resistant JurkatB cells with PSMB5 mutation and their parent cells].

    Science.gov (United States)

    Lü, Shu-Qing; Yang, Jian-Min; Huang, Chong-Mei; Xu, Xiao-Qian; Zhou, Hong; Song, Ning-Xia; Wang, Jian-Min

    2011-08-01

    This study was purposed to investigate the differences of cyto biological characteristics and protein expression levels between bortezomib-resistant T-lymphoblastic lymphoma/leukemia cell lines JurkatB containing PSMB5 G322A mutation and their parent cell line Jurkat, The cytotoxicities of bortezomib and chemotherapeutic drugs to JurkatB5 cells (end selection concentration of bortezomib was 500 nmol/L), JurkatB8 (end selection concentration 800 nmol/L) and Jurkat cells were analyzed. The cell growth curves were drawn with viable cell counts by trypan blue assay, the colony formation rate were assayed by soft-agar colony culture, and the cell distributions in cell cycle were analyzed by flow cytometry, mRNA expression levels of multidrug resistance (MDR) genes MDR1, LRP and MRP were measured by real-time fluorescence quantitative RT-PCR, the differences of protein expression levels were detected by SpringBio antibody microarray containing 720 proteins. The results showed that the drug resistance multiples for 48 hours of JurkatB5 and JurkatB8 cells (relative to Jurkat) to bortezomib were increased by 33.52 and 39.04 times, respectively. JurkatB5 and JurkatB8 cells did not display significant cross-resistance to daunorubicin, adriamycin, vindesine, and etoposide after exposure for 48 hours. There were no significant differences in the cell growth curve, colony formation rate and cell distributions in cell cycle between JurkatB5, JurkatB8 and Jurkat cells (p > 0.05). There were no significant differences of mRNA expression levels of MDR1, LRP, MRP between JurkatB5 and Jurkat cells (p > 0.05). There were 264 analyzable expression points detected by antibody microarray. Among them, 252 protein expression levels were not significantly different between JurkatB5, JurkatB8 and Jurkat cells (II, matrix metalloproteinase-2, tenascin, Golgi complex, involucrin, histone deacetylase 1, perforin, prolactin, retinoic acid receptor β, integrin β-1), but no proteins were detected

  20. In Vitro Study of Ultrasound on Multidrug Resistance in MDR Human Hepatoma HepG2 Cells

    Institute of Scientific and Technical Information of China (English)

    Qiujun Qi; Baojin Zhai; Y