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Sample records for adriamycin

  1. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

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

    2008-09-01

    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/10(4) 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 have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  2. Vascular dysfunction in adriamycin nephrosis : different effects of adriamycin exposure and nephrosis

    NARCIS (Netherlands)

    Ulu, Nadir; Buikema, Hendrik; van Gilst, Wiek H.; Navis, Gerjan

    2008-01-01

    Background. Nephrosis-induced endothelial dysfunction is assumed to play a main role in cardiovascular morbidity. Adriamycin-induced proteinuria is a well-established rat model for nephrotic syndrome. However, induction of nephrosis by intravenous adriamycin administration might exert direct adriamy

  3. Detection of adriamycin-DNA adducts by accelerator mass spectrometry.

    Science.gov (United States)

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

    2010-01-01

    There have been many attempts in the past to determine whether significant levels of Adriamycin-DNA adducts form in cells and contribute to the anticancer activity of this agent. Supraclincal drug levels have been required to study drug-DNA adducts because of the lack of sensitivity associated with many of the techniques employed, including liquid scintillation counting of radiolabeled drug. The use of accelerator mass spectrometry (AMS) has provided the first direct evidence of Adriamycin-DNA adduct formation in cells at clinically relevant Adriamycin concentrations. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection (compared to liquid scintillation counting) and has revealed adduct formation within an hour of drug treatment. The rigorous protocol required for this approach, together with many notes on the precautions and procedures required in order to ensure that absolute levels of Adriamycin-DNA adducts can be determined with good reproducibility, is outlined in this chapter.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Combination Adriamycin and radiation therapy in gynecologic cancers

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    Watring, W.G.; Byfield, J.E.; Lagasse, L.D.; Lee, Y.D.; Juillard, G.; Jacobs, M.; Smith, M.L.

    1974-12-01

    Anthracyclic antibiotics, of which adriamycin is representative, have the ability to bind to cellular DNA and thereby interfere with the X ray repair process. When radiation survival curves of tissue cultures were studied, increased cell-killing was noted in those cultures with adriamycin over those without the drug. The mechanism by which this occurs may be related to a reduced rate of DNA strand break rejoining, as demonstrated by use of alkaline sucrose gradient techniques. A preliminary clinical Phase I study, in which patients with advanced gynecologic malignancy were treated by simultaneous adriamycin and X radiation, suggests that combined therapy is well-tolerated, and that such combinations may prove useful in selected patients.

  7. BIOLOGICAL PROPERTIES OF ADRIAMYCIN BOUND TO BIODEGRADABLE POLYMERIC CARRIERS

    NARCIS (Netherlands)

    HOES, CJT; GROOTOONK, J; DUNCAN, R; HUME, IC; BHAKOO, M; BOUMA, JMW; FEIJEN, J

    1993-01-01

    Three different conjugates having adriamycin (ADR) bound to the side chain carboxyl groups of high-molecular weight poly(alpha-L-glutamic acid) (PGA) either directly or by interpolation of GlyGly and GlyGlyGlyLeu spacers, respectively, were compared with respect to immunogenicity and cytotoxicity in

  8. The effects of topical instillation of adriamycin in bladder tumors of rats fed with FANFT.

    Science.gov (United States)

    Pontes, J E; Izbicki, R; Silberberg, B; Baker, L; Pierce, J M

    1978-01-01

    Topical bladder instillation of adriamycin was evaluated in FANET produced rat tumors produced by diets containing (N-[4-(5-Nitro-2-Furyl)-2-Thiazolyl] Formamide). The drug was ineffective in either preventing or eradicating tumors. The failure of response in this animal model may be related to drug schedule, biological potential of this tumor, or ineffectiveness of Adriamycin in this tumor.

  9. Activation of adriamycin by the pH-dependent formaldehyde-releasing prodrug hexamethylenetetramine.

    Science.gov (United States)

    Swift, Lonnie P; Cutts, Suzanne M; Rephaeli, Ada; Nudelman, Abraham; Phillips, Don R

    2003-02-01

    Previous studies have shown that Adriamycin can react with formaldehyde to yield an activated form of Adriamycin that can further react with DNA to yield Adriamycin-DNA adducts. Because hexamethylenetetramine (HMTA) is known to hydrolyze under cellular conditions and release six molecules of formaldehyde in a pH-dependent manner, we examined this clinical agent for its potential as a formaldehyde-releasing prodrug for the activation of Adriamycin. In IMR-32 neuroblastoma cells in culture, increasing levels of HMTA resulted in enhanced levels of Adriamycin-DNA adducts. These adducts were formed in a pH-dependent manner, with 4-fold more detected at pH 6.5 compared with pH 7.4, consistent with the known acid lability of HMTA. The resulting drug-DNA lesion was shown to be cytotoxic, with combined Adriamycin and prodrug treatment resulting in a 3-fold lower IC(50) value compared with that of Adriamycin alone. Given the acidic nature of solid tumors and the preferential release of formaldehyde from HMTA in acidic environments, HMTA therefore has some potential for localized activation of Adriamycin in solid tumors.

  10. 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.

  11. Effect of Stem Cell Therapy on Adriamycin Induced Tubulointerstitial Injury

    Science.gov (United States)

    Zickri, Maha Baligh; Zaghloul, Somaya; Farouk, Mira; Fattah, Marwa Mohamed Abdel

    2012-01-01

    Background and Objectives It was postulated that adriamycin (ADR) induce renal tubulointerstitial injury. Clinicians are faced with a challenge in producing response in renal patients and slowing or halting the evolution towards kidney failure. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on tubular renal damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. Methods and Results Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of tubular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy, vacuolated cytoplasm, dark nuclei, detached epithelial lining and desquamated nuclei were noticed in few collecting tubules (CT). 10, 20 and 30 days following therapy. The mean count of CT showing desquamated nuclei and mean value of serum creatinine revealed significant difference in ADR group. The mean area% of Prussian blue+ve cells and that of CD105 +ve cells measured in subgroup S1 denoted a significant increase compared to subgroups S2 and S3. Conclusions ADR induced tubulointerstitial damage that regressed in response to cord blood HMSC therapy. PMID:24298366

  12. Tissue Regeneration and Stem Cell Distribution in Adriamycin Induced Glomerulopathy

    Science.gov (United States)

    Zickri, Maha Baligh; Fattah, Marwa Mohamed Abdel; Metwally, Hala Gabr

    2012-01-01

    Background and Objectives Glomerulosclerosis develops secondary to various kidney diseases. It was postulated that adriamycin (ADR) induce chronic glomerulopathy. Treatment combinations for one year did not significantly modify renal function in resistant focal segmental glomerulosclerosis (FSGS). Recurrence of FSGS after renal transplantation impacts long-term graft survival and limits access to transplantation. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on glomerular damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. Methods and Results Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of glomerular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy multiple Malpighian corpuscles (MC) appeared with patent Bowman's space (Bs) 10 and 20 days following therapy. One month following therapy no remarkable shrunken glomeruli were evident. Glomerular area and serum creatinine were significantly different in ADR group in comparison to control and SC therapy groups. Conclusions ADR induced glomerulosclerosis regressed in response to cord blood HMSC therapy. A reciprocal relation was recorded between the extent of renal regeneration and the distribution of undifferentiated mesenchymal stem cells. PMID:24298364

  13. Inhibition of Cyclooxygenase-2 Reduces Hypothalamic Excitation in Rats with Adriamycin-Induced Heart Failure

    OpenAIRE

    2012-01-01

    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...

  14. Adriamycin nephrosis and contrast media; A comparison between diatrizoate and iohexol in rats

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    Thomsen, H.S.; Golman, K.; Hemmingsen, L.; Larsen, S.; Skaarup, P. (Koebenhavns Amts Sygehus, Herlev (Denmark). Dept. of Diagnostic Radiology Koebenhavns Amts Sygehus, Herlev (Denmark). Dept. of Nuclear Medicine Koebenhavns Amts Sygehus, Herlev (Denmark). Inst. of Pathology Centralsygehuset, Nykoebing Falster (Denmark). Dept. of Clinical Chemistry Malmoe Allmaenna Sjukhus (Sweden). Dept. of Experimental Research)

    1990-01-01

    Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused further increased albuminuria of significance, whereas both induced significantly increased excretion of all 5 tubular components. The excretion of NAG and sodium was significantly higher following diatrizoate than following iohexol. From 24 h post injection there was no significantly greater excretion of any of the components after either diatrizoate or iohexol than after saline among the rats given Adriamycin. At the end of day 9 after contrast medium injection neither serum sodium, potassium, glucose, urea, creatinine, nor albumin revealed any contrast media related changes. Kidney histology showed quantitatively larger lesions in kidneys exposed to Adriamycin and contrast media than in kidneys exposed to Adriamycin and saline. There were no differences between the two contrast media groups. It is thus concluded, that both high osmolar ionic and low osmolar non-ionic contrast media cause temporary tubular dysfunction but no further glomerular dysfunction in rats with nephrosis induced by Adriamycin. The histologic findings indicate that both media may worsen non-reversible renal lesions. (orig.).

  15. Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin.

    Science.gov (United States)

    Muñoz-Castañeda, Juan Rafael; Muntané, Jordi; Herencia, Carmen; Muñoz, Maria C; Bujalance, Inmaculada; Montilla, Pedro; Túnez, Issac

    2006-02-01

    Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.

  16. 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.

  17. BAX OVEREXPRESSION ENHANCES APOPTOSIS INDUCED BY ADRIAMYCIN IN HCC-9204 CELLS

    Institute of Scientific and Technical Information of China (English)

    郑建勇; 李江; 李开宗; 王文亮; 王为忠

    2004-01-01

    Objective: To investigate the effect of overexpression of Bax to the sensitivity of human HCC-9204 cells to adriamycin (ADR). Methods: Human cultured hepatocellular carcinoma cell line HCC-9204 was exposed in vitro to adriamycin for various time. An inducible vector containing Bax gene, with ZnSO4 as external inducer was constructed. Cell apoptosis was ascertained by morphological criteria, detection of apoptotic DNA fragmentation by TUNEL assay and flow cytometry. Tetrazolium blue (MTT) assay was used to evaluate the differences in drug sensitivity of HCC-9204 cells after Bax-transfection. Results: HCC-9204 cells treated with adriamycin at 20μmol/L showed extensive cell death. TUNEL assay showed nucleus fragmentation. And apoptotic peak was also shown by flow cytometry. FACS analyses showed a significant sub-G1 peak and apoptosis in 31% cells at 24h after treatment. Furthermore, the time-course of cell viability following exposure of HCC-9204/Bax cells to adriamycin showed that Bax was able to significantly decrease cell survival following exposure to adriamycin.

  18. Verapamil increases the bacteriostatic and bactericidal effects of adriamycin on Escherichia coli.

    Science.gov (United States)

    Abramov, Y; Aronovitch, J; Ramu, A

    1996-01-01

    The purpose of this study was to evaluate the effect of verapamil on adriamycin-resistant and -sensitive Escherichia coli bacterial strains. Two E. coli strains: B-SR9 and K12-KL16 were incubated with adriamycin in various concentrations in the presence or absence of verapamil. Growth and killing rates were measured using optical densities and colonogenic assays. Transmembrane transport capacity was evaluated by measuring radioactively labelled leucine uptake and intracellular potassium concentrations. While adriamycin (ADR) showed both bacteriostatic and bactericidal effects upon the two bacterial strains, the K12 strain was significantly more resistant to the drug than its peer. Subtoxic concentrations of verapamil augmented these effects in both strains. Verapamil affected bacterial transmembrane transport activity and caused potassium leakage through the cell membrane. Simultaneous exposure to adriamycin and verapamil resulted in rapid, massive damage to membrane functions, indicating accelerated killing rate. The authors concluded that verapamil acts as a potentiator of adriamycin's cytotoxicity in E. coli bacteria in a manner similar to that in multidrug resistant mammalian tumour cells. This observation suggests that the mechanisms of resistance to the drug may be similar in both species.

  19. Reduced DNA topoisomerase II activity and drug-induced DNA cleavage activity in an adriamycin-resistant human small cell lung carcinoma cell line

    NARCIS (Netherlands)

    de Jong, Steven; Zijlstra, J G; de Vries, Liesbeth; Mulder, Nanno

    1990-01-01

    In a previous study we suggested that, in addition to the reduced Adriamycin accumulation, part of the resistance in an Adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) could be explained by supposing a changed Adriamycin-DNA-topoisomerase II (Topo II) interaction. The prese

  20. Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells.

    Science.gov (United States)

    Takahashi, Tsutomu; Furuchi, Takemitsu; Naganuma, Akira

    2006-12-15

    To elucidate the mechanism of acquired resistance to Adriamycin, we searched for genes that, when overexpressed, render Saccharomyces cerevisiae resistant to Adriamycin. We identified AKL1, a gene of which the function is unknown but is considered, nonetheless, to be a member of the Ark/Prk kinase family, which is involved in the regulation of endocytosis, on the basis of its deduced amino acid sequence. Among tested members of the Ark/Prk kinase family (Ark1, Prk1, and Akl1), overexpressed Prk1 also conferred Adriamycin resistance on yeast cells. Prk1 is known to dissociate the Sla1/Pan1/End3 complex, which is involved in endocytosis, by phosphorylating Sla1 and Pan1 in the complex. We showed that Akl1 promotes phosphorylation of Pan1 in this complex and reduces the endocytic ability of the cell, as does Prk1. Sla1- and End3-defective yeast cells were also resistant to Adriamycin and overexpression of Akl1 in these defective cells did not increase the degree of Adriamycin resistance, suggesting that Akl1 might reduce Adriamycin toxicity by reducing the endocytic ability of cells via a mechanism that involves the Sla1/Pan1/End3 complex and the phosphorylation of Pan1. We also found that HEK293 cells that overexpressed AAK1, a member of the human Ark/Prk family, were Adriamycin resistant. Our findings suggest that endocytosis might be involved in the mechanism of Adriamycin toxicity in yeast and human cells.

  1. Application of magnetic resonancetomographic angiography in treatment of trigeminal neuralgia with Adriamycin

    Institute of Scientific and Technical Information of China (English)

    Bin Xu; Yong Zhang; Ni-Ka Chen; Lu-Ming Chen; Yang-Kui Ou

    2016-01-01

    Objective:To observe the application value of magnetic resonancetomographic angiography (MRTA) in the treatment of primary trigeminal neuralgia with Adriamycin and to explore its pathogenesis.Methods:A total of 53 cases of primary trigeminal neuralgia without aberrant blood vessels oppressed trigeminal nerve were screened out by MRTA and was treated with Adriamycin. Another 62 former cases with primary trigeminal neuralgia treated by Adriamycin served as control. The treating efficacy and the recurrence rate of 3 and 6 months past were observed.Results:The efficacy of two groups after 14 d showed no difference. The recurrence rates of the observation group was significantly lower than the control on the both.Conclusions:The patients without trigeminal nerve oppressed by aberrant blood vessels by MRTA screening show low in recurrence rate and part of them seems to have self-healing mechanism.

  2. Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.

  3. Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Sheng Sun; Jiang-Hao Chen; Rui Ling; Qing Yao; Ling Wang; Zhong Ma; Yu Li

    2006-01-01

    AIM: To observe the therapeutic effects of liposomeencapsulated adriamycin (LADM) on hepatoma in comparison with adriamycin solution (FADM) and adriamycin plus blank liposome (ADM + BL) administered into the hepatic artery of rats.METHODS: LADM was prepared by pH gradient-driven method. Normal saline, FADM (2 mg/kg), ADM+BL (2 mg/kg), and LADM (2 mg/kg) were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma,which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time,tumor enlargement ratio, and tumor necrosis degree.The difference was determined with ANOVA and Dunnett test and log rank test.RESULTS: Compared to FADM or ADM + BL, LADM produced a more significant tumor inhibition (tumor volume ratio: 1.243 ± 0.523 vs 1.883 ± 0.708, 1.847 ± 0.661,P < 0.01), and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM+BL (231.48 v's 74.66, 94.70) (P < 0.05).CONCLUSION: The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

  4. 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.

  5. [Reversal of adriamycin resistance by digoxin in human breast cancer cell line MCF-7/adriamycin and its mechanism].

    Science.gov (United States)

    Li, Bai-He; Yuan, Lei; Shi, Ran-Ran; Wang, Jian-Guo

    2015-12-25

    The aim of this study was to investigate the effects of digoxin on the chemoresistance of human breast cancer cell line MCF-7/adriamycin (ADR) and its underlying mechanism. MCF-7 and MCF-7/ADR cells were designated as control and ADR groups, respectively. MCF-7/ADR cells in ADR + digoxin group received 48 h of digoxin (10 nmol/L) treatment; MCF-7/ADR cells transfected with pLKO.1-shHIF-1α and pLKO.1-shcontrol plasmids were named shHIF-1α and shcontrol groups, respectively. CCK-8 assay was employed to detect the cytotoxic effect of ADR on MCF-7/ADR cells, and IC50 value and resistance index were calculated according to CCK-8. RT-PCR was used to measure the mRNA levels of hypoxia inducible factor-1α (HIF-1α) and multidrug resistance-1 (MDR1). Western blot was used to analyze the protein levels of HIF-1α and MDR1. Flow cytometry was used to determine the apoptosis. The result showed that the resistance index of MCF-7/ADR cells was 115.6, and it was reduced to 47.2 under the action of digoxin (P Digoxin reduced the protein levels of HIF-1α and MDR1, as well as the mRNA level of MDR1, but did not affect the mRNA level of HIF-1α. After HIF-1α gene was silenced, the protein levels of HIF-1α and MDR1 were down-regulated (P digoxin promoted cell apoptosis in both shcontrol and shHIF-1α groups, the difference between the two groups was not significant. In conclusion, the results suggest that digoxin may partially reverse the ADR resistance in human breast cancer cell line MCF-7/ADR by means of down-regulating the expression levels of HIF-1α and MDR1 and promoting apoptosis via HIF-1α-independent pathway.

  6. [Enhancement of reversing drug resistance of K562/A02 cells to adriamycin by ultrasound-induced cavitation].

    Science.gov (United States)

    Chen, Bao-An; Meng, Qing-Qi; Wu, Wei; Gao, Feng; Shao, Ze-Ye; Ding, Jia-Hua; Gao, Chong; Sun, Xin-Chen; Cheng, Hong-Yan; Sun, Yun-Yu; Wang, Jun; Cheng, Jian; Zhao, Gang; Song, Hui-Hui; Bao, Wen; Ma, Yan; Wang, Xue-Mei

    2008-12-01

    This study was aimed to investigate the effects of low frequency and power ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell line K562/A02 in vitro, to find out the parameters of optimal exposure, and to explore the possible mechanism reversing drug-resistance of K562/A02 cells. The K562/A02 cells in logarithmic growth phase were used in experiments. The experiments were divided into 4 groups: group control, group adriamycin (A02) alone, group ultrasound (US) alone and group A02+US. The trypan blue dye exclusion test and MTT assay were used to determine the cell viability; Wright's staining was used to detect the apoptosis; the flow cytometry was used to analyze the drug concentration, and the scanning electron microscopy was used to observe the changes of cell surface. The results showed that the significant differences in cell viability, intracellular adriamycin concentration and changes of cell membrane were found between ultrasound-treated and untreated cells in the presence of various concentration of adriamycin. The exposure to ultrasound at 20 kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60 seconds could kill K562/A02 cells at once. After being treated by low frequency ultrasound, the small holes with diameter about 1-2 microm in the cell surface appeared. The ultrasound increased the adriamycin concentration in the cells, accelerated the formation of apoptotic bodies, and promoted apoptosis of adriamycin-resistant cells. It is concluded that the ultrasound at optimal parameters enhances inhibitory effect of adriamycin on drug-resistant cell line, thereby reverses drug-resistance of drug-resistant cell line through sound-hole effect in tumor cells resulting from ultrasound induced cavitation.

  7. Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice

    Institute of Scientific and Technical Information of China (English)

    SHEN Liang-fang; ZHANG Yang-de; SHEN Hai-ju; ZENG Shan; WANG Xin; WANG Cheng; LE Yuan; SHEN Hong

    2006-01-01

    Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicityof the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs arecurrently under hot investigation with great clinical significance. This study was aimed to investigate thedifferent tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the micebody after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in differentdiameters on normal mice liver.Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in eachgroup (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycininjection was employed as the control group). A single dose of either conjugated or free adriamycin equaled2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectivelycollected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquidchromatography with fluorescence detector.Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatmentgroups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. Theadriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher thanthat in the control group, except for the group with the nanoparticles diameters of (22.3±6.2) nm (P<0.05). TheADM-PBCA-NP in (101.0±20.3) nm diameter had the highest liver distribution, and the second highestadriamycin distribution in liver was the group of (143.0±23.5) nm diameter (P<0.05). Moreover, adriamycinwas released slowly in the liver during the detection period in the experimental groups. ADM

  8. [Contractile function of the isolated heart in chronic adriamycin-induced myocardial lesions].

    Science.gov (United States)

    Kapel'ko, V I; Popovich, M I; Golikov, M A; Novikova, N A; Shul'zhenko, V S

    1987-07-01

    Adriamycin, administered to rats for 4 weeks, caused insufficiency of isolated heart contractility with a twofold reduction of cardiac output in surviving animals. The same cumulative dose of adriamycin, administered to rats over 10 weeks, was not associated with any significant reduction of the heart's pumping function. However, heart rate increase by atrial electrostimulation that shortened the diastolic pause to a control level, also reduced the minute and stroke volumes by 38%, as compared to the controls. All animals showed increased diastolic stiffness of the left ventricle that must have interfered with its filling, particularly so in case of low inflow pressure, and disturbed atrial automaticity, as reflected in bradicardia in rats and supraventricular arrhythmia in guinea pigs.

  9. Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

    Science.gov (United States)

    Conte, P F; Bruzzone, M; Chiara, S; Rosso, R; Giaccone, G; Carnino, F; Guercio, E; Ragni, N; Foglia, G; Bentivoglio, G

    1988-04-30

    Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

  10. Endothelin receptor a blockade is an ineffective treatment for adriamycin nephropathy.

    Science.gov (United States)

    Tan, Roderick J; Zhou, Lili; Zhou, Dong; Lin, Lin; Liu, Youhua

    2013-01-01

    Endothelin is a vasoconstricting peptide that plays a key role in vascular homeostasis, exerting its biologic effects via two receptors, the endothelin receptor A (ETA) and endothelin receptor B (ETB). Activation of ETA and ETB has opposing actions, in which hyperactive ETA is generally vasoconstrictive and pathologic. Selective ETA blockade has been shown to be beneficial in renal injuries such as diabetic nephropathy and can improve proteinuria. Atrasentan is a selective pharmacologic ETA blocker that preferentially inhibits ETA activation. In this study, we evaluated the efficacy of ETA blockade by atrasentan in ameliorating proteinuria and kidney injury in murine adriamycin nephropathy, a model of human focal segmental glomerulosclerosis. We found that ETA expression was unaltered during the course of adriamycin nephropathy. Whether initiated prior to injury in a prevention protocol (5 mg/kg/day, i.p.) or after injury onset in a therapeutic protocol (7 mg/kg or 20 mg/kg three times a week, i.p.), atrasentan did not significantly affect the initiation and progression of adriamycin-induced albuminuria (as measured by urinary albumin-to-creatinine ratios). Indices of glomerular damage were also not improved in atrasentan-treated groups, in either the prevention or therapeutic protocols. Atrasentan also failed to improve kidney function as determined by serum creatinine, histologic damage, and mRNA expression of numerous fibrosis-related genes such as collagen-I and TGF-β1. Therefore, we conclude that selective blockade of ETA by atrasentan has no effect on preventing or ameliorating proteinuria and kidney injury in adriamycin nephropathy.

  11. Endothelin receptor a blockade is an ineffective treatment for adriamycin nephropathy.

    Directory of Open Access Journals (Sweden)

    Roderick J Tan

    Full Text Available Endothelin is a vasoconstricting peptide that plays a key role in vascular homeostasis, exerting its biologic effects via two receptors, the endothelin receptor A (ETA and endothelin receptor B (ETB. Activation of ETA and ETB has opposing actions, in which hyperactive ETA is generally vasoconstrictive and pathologic. Selective ETA blockade has been shown to be beneficial in renal injuries such as diabetic nephropathy and can improve proteinuria. Atrasentan is a selective pharmacologic ETA blocker that preferentially inhibits ETA activation. In this study, we evaluated the efficacy of ETA blockade by atrasentan in ameliorating proteinuria and kidney injury in murine adriamycin nephropathy, a model of human focal segmental glomerulosclerosis. We found that ETA expression was unaltered during the course of adriamycin nephropathy. Whether initiated prior to injury in a prevention protocol (5 mg/kg/day, i.p. or after injury onset in a therapeutic protocol (7 mg/kg or 20 mg/kg three times a week, i.p., atrasentan did not significantly affect the initiation and progression of adriamycin-induced albuminuria (as measured by urinary albumin-to-creatinine ratios. Indices of glomerular damage were also not improved in atrasentan-treated groups, in either the prevention or therapeutic protocols. Atrasentan also failed to improve kidney function as determined by serum creatinine, histologic damage, and mRNA expression of numerous fibrosis-related genes such as collagen-I and TGF-β1. Therefore, we conclude that selective blockade of ETA by atrasentan has no effect on preventing or ameliorating proteinuria and kidney injury in adriamycin nephropathy.

  12. 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.

  13. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Ding

    2014-01-01

    Full Text Available Previous studies reported the oral administration of Naja naja atra venom (NNAV reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  14. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom.

    Science.gov (United States)

    Ding, Zhi-Hui; Xu, Li-Min; Wang, Shu-Zhi; Kou, Jian-Qun; Xu, Yin-Li; Chen, Cao-Xin; Yu, Hong-Pei; Qin, Zheng-Hong; Xie, Yan

    2014-01-01

    Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180  μ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ruckdeschel, J.C.; Baxter, D.H.; McKneally, M.F.; Killam, D.A.; Lunia, S.L.; Horton, J.

    1979-08-01

    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/M/sup 2/ iv, d. 1,8; Adriamycin 20 mg/M/sup 2/ iv, d. 1,8; Methotrexate 15 mg/M/sup 2/ iv, d. 1,8 and Procarbazine 100 mg/M/sup 2/ 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.

  16. Vincristine, adriamycin, and mitomycin (VAM) therapy for previously treated breast cancer. A preliminary report.

    Science.gov (United States)

    Oster, M W; Park, Y

    1983-01-15

    Fifteen patients with metastatic breast cancer previously treated with chemotherapy were treated with a regimen consisting of vincristine, Adriamycin, and mitomycin. Eleven patients (73%) responded with three complete and eight partial responses. The median duration of response was eight months. While all four nonresponders died within five months, the median duration of survival of responders was 18 months. Toxicity was significant but tolerable. Thus, this preliminary report suggests that this regimen is active in advanced previously treated breast cancer, providing meaningful remissions with acceptable toxicity.

  17. Adriamycin does not affect the repair of X-ray induced DNA single strand breaks

    Energy Technology Data Exchange (ETDEWEB)

    Cantoni, O.; Sestili, P.; Cattabeni, F.

    1985-06-01

    The ability of the antitumor antibiotic adriamycin (Ad) to inhibit the rejoining of DNA single strand breaks produced by X-rays was investigated in cultured cells. Chinese hamster ovary cells were given 400 rad and were allowed to repair in the presence or absence of Ad for 60 min at 37degC. The drug did not affect the ability of cells to repair DNA breaks and residual breaks found after the repair period were attributed to those induced by Ad alone. (author). 16 refs.

  18. 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...

  19. 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...

  20. Redox kinetics of adriamycin adsorbed on the surface of graphite and mercury electrodes.

    Science.gov (United States)

    Komorsky-Lovrić, Sebojka

    2006-09-01

    Kinetics of the surface redox reactions of adriamycin (doxorubicin hydrochloride) adsorbed on paraffin-impregnated graphite electrode (PIGE) and on mercury electrode is measured by square-wave voltammetry. In 0.9 mol/L KNO3 buffered to pH 4.65, the standard electrode reaction rate constants of the first quinone/hydroquinone redox couple (see Scheme 2) on PIGE and mercury are k(s1)=49+/-12 s(-1) and k(s1)=147+/-36 s(-1), respectively. Under the same conditions, the standard rate constant of the second redox couple on the PIGE is smaller than 4 s(-1) and the electron transfer coefficient of the reduction is alpha2=0.35.

  1. Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients.

    Science.gov (United States)

    Forgeson, G. V.; Selby, P.; Lakhani, S.; Zulian, G.; Viner, C.; Maitland, J.; McElwain, T. J.

    1988-01-01

    Forty-five patients with relapsed or refractory multiple myeloma received continuous infusions of vincristine (0.4 mg total dose daily for 4 days) and adriamycin (9 mg m-2 daily for 4 days) with a high dose of methylprednisolone (1 g m-2 i.v. or p.o. daily by 1 h infusion), the VAMP regimen. Sixteen (36%) responded, with a median duration of remission of 11 months and median survival of 20 months. Major toxicities encountered were infective and cardiovascular. Two smaller groups of myeloma patients were treated with high dose methylprednisolone (HDMP) alone, or VAMP plus weekly low dose cyclophosphamide (Cyclo-VAMP). HDMP produced short responses in 25% of patients with less toxicity than VAMP. Cyclo-VAMP was used in a highly selected group of patients who had previously responded to high dose melphalan. It was well tolerated and produced responses in 61% of this group. PMID:3207601

  2. Detection of adriamycin cardiotoxicity with indium-111 labeled antimyosin monoclonal antibody imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takehiko; Matsumori, Akira; Tamaki, Nagara; Morishima, Shigeru; Watanabe, Yuji; Yonekura, Yoshiharu; Endo, Keigo; Konishi, Junji; Kawai, Chuichi (Kyoto Univ. (Japan). Faculty of Medicine)

    1991-04-01

    Myocardial imaging with indium-111 labeled antimyosin monoclonal antibody (antimyosin imaging) has been reported to be useful in the noninvasive detection of myocardial cell necrosis in dilated cardiomyopathy as well as in myocardial infarction and myocarditis. We used antimyosin imaging to detect myocardial damage in 2 patients with malignant lymphoma in whom adriamycin cardiotoxicity was suspected. Patients were injected with 74 MBq of indium-111 labeled antimyosin (Fab. fraction). Forty-eight hours later, planar imaging and single-photon emission computed tomography were performed using a gamma camera with a medium energy general purpose collimator. Antimyosin imaging demonstrated diffuse myocardial uptake not only in one patient with congestive heart failure but also in another patient at the early stage without congestive heart failure. Antimyosin imaging may be a sensitive method for noninvasive visualization of myocardial cell damage and useful in the early diagnosis of specific heart muscle disease. (author).

  3. 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.

  4. Inositol hexaphosphate (IP6) enhances the anti-proliferative effects of adriamycin and tamoxifen in breast cancer.

    Science.gov (United States)

    Tantivejkul, Kwanchanit; Vucenik, Ivana; Eiseman, Julie; Shamsuddin, AbulKalam M

    2003-06-01

    The current treatment of breast carcinomas recognizes the importance of combination therapy in order to increase efficacy and decrease side effects of conventional chemotherapy. Inositol hexaphosphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has shown a significant anti-cancer effect in various in vivo and in vitro models, including breast cancer. In this study, we investigated the in vitro growth inhibitory activity of IP6 in combination with adriamycin or tamoxifen, against three human breast cancer cell lines: estrogen receptor (ER) alpha-positive MCF-7, ER alpha-negative MDA-MB 231 and adriamycin-resistant MCF-7 (MCF-7/Adr) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Much lower concentrations of IP6 were required after 96 h of treatment to inhibit the growth of MCF-7/Adr cells than MCF-7 cells; the IC50 for MCF-7/Adr cells was 1.26 mM compared to 4.18 mM for MCF-7 cells. The ER-negative MDA-MB 231 cells were also highly sensitive to IP6 with IC50 being 1.32 mM. To determine the effects of IP6 in combination with either adriamycin or tamoxifen, the median effect principle and Webb's fraction method were used to determine the combination index (CI) and the statistical differences. Growth suppression was markedly increased when IP6 was administered prior to the addition of adriamycin, especially against MCF-7 cells (CI = 0.175 and p IP6 was administered after tamoxifen in all three cell lines studied (CI = 0.343, 0.701 and 0.819; p IP6 with LC50 values ranging from 0.91 to 5.75 mM (n = 10). Our data not only confirm that IP6 alone inhibits the growth of breast cancer cells; but it also acts synergistically with adriamycin or tamoxifen, being particularly effective against ER alpha-negative cells and adriamycin-resistant cell lines.

  5. Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats.

    Science.gov (United States)

    Sakr, Saber A; Abo-El-Yazid, Samah M

    2012-11-01

    The purpose of this work was to evaluate the effect of aqueous extract of fenugreek seeds against hepatotoxicity induced in albino rats by the anticancer drug adriamycin (ADR). Animals were given single dose of ADR (10 mg/kg body weight) and were killed after 2 and 4 weeks. Liver of ADR-treated animals showed histopathological and biochemical alterations. The histopathological changes include hepatic tissue impairment, cytoplasmic vacuolization of the hepatocytes, congestion of blood vessels, leucocytic infiltrations and fatty infiltration. Moreover, the expression of proliferating cell nuclear antigen was increased in ADR-treated rats. The liver enzymes, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were increased in the sera of treated rats. Moreover, ADR significantly increased the concentration of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD) and catalase (CAT) in hepatic tissue. Treating animals with ADR and aqueous extract of fenugreek (0.4 g/kg body weight) seeds led to an improvement in histological and biochemical alterations induced by ADR. The biochemical results showed that AST and ALT appeared normal together with reduction in the level of MDA (lipid peroxidation marker) and increase in SOD and CAT activities. It was concluded from this study that the aqueous extract fenugreek seeds has a beneficial impact on ADR-induced hepatotoxicity due to its antioxidant effect in albino rats.

  6. Change and significance of nuclear factor-κB in adriamycin induced cardiomyopathy in rats

    Institute of Scientific and Technical Information of China (English)

    LI Hong-li; LIU Bin; ZHOU Ling-wang; YU Wei-han

    2005-01-01

    Background This study aimed at investigating the change and significance of nuclear factor-κB (NF-κB) in cardiomyopathy induced by adriamycin (ADR) in rats.Methods Sixty male Wistar rats were randomly divided into three groups: control, ADR and ADR+pyrrolidine dithiocarbamate (PDTC) groups. After 30-day experiment, myocardial histopathological observation was performed. Location and distribution of NF-κB p50 was examined by immunohistochemical assay. Expression of NF-κB p50 protein was examined by immunobolt assay. Electrophoretic Mobility Shift Assay examined activity of NF-κB; Myocardium p53 gene expression was examined by RT-PCR analysis. Results The myocardial lesions of rats were less pronounced in ADR +PDTC group than in ADR group. Compared with control group, there were many myocardium nucleuses, which expressed NF-κB p50 and distribute under epicardium. Expression of NF-κB p50 protein in nucleus increased significantly in ADR group. The NF-κB binding activity increased significantly in ADR group. Myocardium expressions of p53 mRNA increased in ADR group. Conclusions The NF-κB binding activity increased significantly in cardiomyopathy induced by ADR in rats. Moreover, NF-κB plays an important role in causing degeneration of myocardial tissue and regulating expression of related-apoptosis genes.

  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. [Effect of gross saponins of Tribulus terrestris on cardiocytes impaired by adriamycin].

    Science.gov (United States)

    Zhang, Shuang; Li, Hong; Xu, Hui; Yang, Shi-Jie

    2010-01-01

    This study is to observe the protection of gross saponins of Tribulus terrestris (GSTT) on cardiocytes impaired by adriamycin (ADR) and approach its mechanism of action. Cardiocytes of neonate rat were cultivated for 72 hours and divided into normal control group, model (ADR 2 mg x L(-1)) group, and GSTT (100, 30, and 10 mg x L(-1)) groups. MTT colorimetric method was deployed to detect cardiocyte survival rate, activities of CK, LDH, AST, SOD, MDA and NO were detected, and apoptosis was detected with flow cytometry. Effect of GSTT on caspase-3 was detected with Western blotting. Compared with control group, contents of CK, LDH, AST, MDA and NO were increased, and activity of SOD was reduced (P < 0.05, P < 0.01, P < 0.001) by ADR. Numbers of survival cells were increased (P < 0.05, P < 0.001), contents of CK, LDH, AST, MDA and NO were decreased, and activity of SOD was increased (P < 0.05, P < 0.01, P < 0.001) by GSTT (100 and 30 mg x L(-1)). Apoptosis of cardiocytes and concentration of caspase-3 can be reduced by GSTT (100 and 30 mg x L(-1)). GSTT can protect cardiocytes impaired by ADR, which are possible involved with its effect of resisting oxygen free radical.

  10. 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

  11. Assessment of the autonomic nervous injury by adriamycin using the analysis of heart rate variability

    Energy Technology Data Exchange (ETDEWEB)

    Matsukawa, Seishirou [Toho Univ., Tokyo (Japan). Omori Hospital

    1998-06-01

    Analysis of the heart rate variability were carried out for the cases with malignant tumors of the erythropoietic organ who received adriamycin (ADR), and the effects of ADR on the autonomic nervous of these patients were studied. Seven of 35 cases were examined for the consecutive heart rate variability and {sup 123}I-metaiodobenzylguanidine (MIBG) myocardial SPECT, after the administration of ADR. TP value, LF value, LF/HF and SDANN value were 1,448 msec{sup 2}, 354 msec{sup 2}, 2.0 and 97 msec, respectively, indicating that these values were significantly lower than the healthy controls (the C group) (P<0.01). Consecutive observation for 7 cases of ADR group revealed that TP value decreased from 1,489 msec{sup 2} to 1,058 msec{sup 2}, and HF value decreased from 191 msec{sup 2} to 123 msec{sup 2}, significantly (P<0.05). On the other hand, the washout rate of left ventricle which was estimated from MIBG myocardial SPECT increased from 22{+-}14% to 32{+-}14%, significantly (P<0.05). Though cumulative mean dosage of ADR was 286{+-}148 mg/m{sup 2}, sympathetic nervous injury and parasympathetic nervous was caused by such dose ADR, when examinated by the analysis of the heart rate variability and MIBG myocardial SPECT. It is possible to estimate the myocardial injury of heart autonomic nervous that precedes the injury of heart muscle by ADR, by analyzing the heart rate variability, when the cases with malignant tumors are subject to the chemotherapy. Thus it was suggested that the death by arrhythmia and the irreversible myocardial injury might be predictable. (author)

  12. The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line

    OpenAIRE

    2011-01-01

    Abstract Background The purpose of this study was to identify the affect on the proliferation Eca-109 cells treated with oxidized low-density lipoprotein (ox-LDL) combined with adriamycin (ADM). Methods Eca-109 cell were cultured in the presence of oxLDL/ADM, and cell proliferation tested by MTT and cell apoptosis was monitored by the proportion of apoptosis and cell cycle by flow cytomester. We simultaneously evaluated the level of associated- apoptosis Bcl-2, Bax, and Caspase-3 gene mRNA an...

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

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    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

  14. EFFECT OF HIGH-LIPID DIET ON GLOMERULAR MESANGIAL MATRIX IN ADRIAMYCIN-INDUCED NEPHROTIC RATS

    Institute of Scientific and Technical Information of China (English)

    宋红梅; 李学旺; 魏珉; 朱传酉

    2002-01-01

    Objective. To determine the effect of hypercholesterolemia induced by a high-lipid diet on glomerulosclerosis. Methods. Twenty nephrotic syndrome (NS) Wistar rats administrated adriamycin (ADR) with a single intravenous dose of 5 mg/kg body weight, were divided into the standard and high-lipid chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as control. Urinary protein excretion and serum cholesterol were assayed; image analysis and techniques of pathology, immunohistochemistry, and molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrices in different groups. Results. The serum total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS [(2.2 ± 0.3) g/L vs. (0.9 ± 0.1) g/L, P<0.01] and NS [(9.5± 0.2) g/L vs. (2.3 ± 0.3) g/L, P<0.01]. The urinary protein excretion was significantly higher in the high-lipid diet rats than in standard chow rats[(76.2± 24.2) mg/24 h vs. (44.8 ± 13.6) mg/24 h, P<0.05] in NS rats. Although increases in the mesangial matrix and mesangial cells were observed in rats with high-lipid diet in both NS and non-NS group, more obvious pathological changes were found in NS group, such as lipid deposits and foam cell formation in mesangial areas, and progressing to focal and segmental glomerulosclerosis in some glomeruli. The immunohistochemical assay showed that the production of 3 major components (collagen IV, fibronectin, and laminin) was increased in NS group, especially in the rats with high-lipid chow. The increased expression of laminin mRNA was also detected with slot blotting in both NS and non-NS rats with high-lipid chow, and it was more obvious in the rats with NS. Conclusion. Our findings indicated that diet-induced hyperlipidemia can lead to over-production of mesangial matrix components, and further aggravate glomerulosclerosis in ADR-induced nephrosis.

  15. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma

    NARCIS (Netherlands)

    H.M. Lokhorst; B. van der Holt; S. Zweegman; E. Vellenga; S. Croockewit; M.H. van Oers; P. von dem Borne; P. Wijermans; R. Schaafsma; O. de Weerdt; S. Wittebol; M. Delforge; H. Berenschot; G.M. Bos; K.S.G. Jie; H. Sinnige; M. van Marwijk-Kooy; P. Joosten; M.C. Minnema; R. van Ammerlaan; P. Sonneveld

    2010-01-01

    The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone

  16. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma

    NARCIS (Netherlands)

    H.M. Lokhorst (Henk); B. van der Holt (Bronno); S. Zweegman (Sonja); E. Vellenga (Edo); S. Croockewit (Sandra); M.H.J. van Oers (Marinus); P.A. von dem Borne (P. A.); P.W. Wijermans (Pierre); R. Schaafsma (Ron); O. de Weerdt (O.); S. Wittebol (Shulamit); M. Delforge (Michel); H. Berenschot (Henriëtte); G.M. Bos (Gerard); K.S-G. Jie; H. Sinnige (Harm); M. van Marwijk Kooy (Marinus); P. Joosten (Peter); M.C. Minnema (Monique); R.A.H.M. Ammerlaan (Rianne); P. Sonneveld (Pieter)

    2010-01-01

    textabstractThe phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and d

  17. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Holt, B. van der; Zweegman, S.; Vellenga, E.; Croockewit, S.; Oers, M.H. van; Borne, P. von dem; Wijermans, P.; Schaafsma, R.; Weerdt, O. de; Wittebol, S.; Delforge, M.; Berenschot, H.; Bos, G.M.; Jie, K.S.; Sinnige, H.; Marwijk-Kooy, M. van; Joosten, P.; Minnema, M.C.; Ammerlaan, R. van; Sonneveld, P.

    2010-01-01

    The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone

  18. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time

    NARCIS (Netherlands)

    Kramer, Andrea B.; van Timmeren, Mirjan M.; Schuurs, Theo A.; Vaidya, Vishal S.; Bonventre, Joseph V.; van Goor, Harry; Navis, Gerjan

    2009-01-01

    Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H, Navis G. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time. Am J Physiol Renal Physiol 296: F1136-F1145, 2009. First published February

  19. Safety and efficacy of a combination therapy with Revlimid, Adriamycin and dexamethasone (RAD) in relapsed/refractory multiple myeloma (MM): a single-centre experience

    OpenAIRE

    Caravita, Tommaso; Siniscalchi, Agostina; Tendas, Andrea; Cupelli, Luca; Ales, Micaela; Perrotti, Alessio; Niscola, Pasquale; De Fabritiis, Paolo

    2010-01-01

    Safety and efficacy of a combination therapy with Revlimid, Adriamycin and dexamethasone (RAD) in relapsed/refractory multiple myeloma (MM): a single-centre experience phone: +39-065-1008983 (Siniscalchi, Agostina) (Siniscalchi, Agostina) Department of Hematology S. Eugenio Hospital, ?Tor Vergata? University - Piazzale dell?Umanesimo, 10 - 00100 - Rome - ITALY (Caravita, Tommaso) Department of Hematology S. Eugenio Hospital, ?Tor Vergata? University - Piazz...

  20. Adverse Renal Effects of the AGE Inhibitor Pyridoxamine in Combination with ACEi in Non-Diabetic Adriamycin-Induced Renal Damage in Rats

    NARCIS (Netherlands)

    Waanders, Femke; van Goor, Harry; Navis, Gerjan

    2008-01-01

    Background/Aims: Advanced glycation end products (AGEs) are involved in diabetic nephropathy. The AGE inhibitor pyridoxamine (PM) is renoprotective in experimental chronic allograft nephropathy supporting its potential in non-diabetic renal damage. Methods: We studied the effects of PM in adriamycin

  1. Therapeutic effect of ozone and rutin on adriamycin-induced testicular toxicity in an experimental rat model.

    Science.gov (United States)

    Salem, E A; Salem, N A; Hellstrom, W J

    2017-02-01

    To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)-induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C-reactive protein, monocyte chemoattractant proteins-1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels.

  2. [A case of sarcomatoid malignant peritoneal mesothelioma responding to combination chemotherapy of cyclophosphamide, vincristine, adriamycin and dacarbazine(CYVADIC)].

    Science.gov (United States)

    Kusama, Toshiyuki; Kodaka, Taiichi; Tsunemine, Hiroko; Akasaka, Hiroshi; Koizumi, Naoki; Fujimoto, Koji; Sakano, Shigeru; Ito, Rieko; Kondo, Takeshi; Kitazawa, Sohei; Yamamura, Hisako; Takahashi, Katsuhito

    2009-03-01

    A 66-year-old woman was seen at our hospital because of abdominal fullness. A computed tomography(CT)revealed massive tumors in abdominal cavity. The patient underwent surgery consisting of tumorectomy, segmental gastrectomy, partial resection of small intestin, transverse colectomy, left oophorectomy and gastrostomy. By using immunohistochemical staining, the patient was diagnosed as sarcomatoid malignant peritoneal mesothelioma. Rapidly abdominal fullness occurred as of 22 days after the operation, and an abdominal CT revealed the massive recurrent tumors. We started a combination chemotherapy of cyclophosphamide, vincristine, adriamycin and dacarbazine (CYVADIC). The recurrent tumors showed remarkable reduction after the two courses of CYVADIC chemotherapy. Although we next started carboplatin and paclitaxel combination chemotherapy, she died due to rapidly progression of the disease with disseminated intravascular coagulation after 132 days of the operation. Malignant mesothelioma, especially sarcomatoid mesothelioma, is known to have a poor prognosis. However, our case suggests that we could improve the prognosis of sarcomatoid malignant mesothelioma by aggressive chemotherapy.

  3. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin.

    Science.gov (United States)

    Gewirtz, D A

    1999-04-01

    The mechanisms responsible for the antiproliferative and cytotoxic effects of the anthracycline antibiotics doxorubicin (Adriamycin) and daunorubicin (daunomycin) have been the subject of considerable controversy. This commentary addresses the potential role of DNA synthesis inhibition, free radical formation and lipid peroxidation, DNA binding and alkylation, DNA cross-linking, interference with DNA strand separation and helicase activity, direct membrane effects, and the initiation of DNA damage via the inhibition of topoisomerase II in the interaction of these drugs with the tumor cell. One premise underlying this analysis is that only studies utilizing drug concentrations that reflect the plasma levels in the patient after either bolus administration or continuous infusion are considered to reflect the basis for drug action in the clinic. The role of free radicals in anthracycline cardiotoxicity is also discussed.

  4. Local administration of liposomal adriamycin inhibited proliferation of metastatic cells in axillary lymph nodes in rabbit breast cancer model

    Institute of Scientific and Technical Information of China (English)

    Li Xiaojun; Qin Hong; Yao Jia; Wang Jiansheng; Xian Yinsheng; Zhang Yunfeng; Ren Hong

    2009-01-01

    Objective: To assess the inhibitory effects of liposomal adriamycin (LADR) locally injected into mammary glands of VX2 tumor-bearing rabbits on proliferation of lymph nodal metastatic cells. Methods: Twenty-one VX2 tumor-bearing rabbits were randomly and equally divided into 3 groups. Rabbits were randomized to receive sham treatment (Group I), subcutaneous LADR around tumor (Group II) and intravenous free adriamycin (Group III), respectively. Breast tumor and axillary lymph nodes were harvested after 3 repeated treatment. Nodal sizes of both pre- and post-treatment were measured. Proliferating cell nuclear antigen (PCNA) mRNA in both tumor and lymph nodes were determined by RT-PCR. Results: The mean size of axillary lymph nodes in Group I, II and III increased by 3.70%, 1.55% and 2.89%, respectively, with significant difference between Group III and I (P=0.004) and between Group II and III (P=0.002). Relative expression values of PCNA mRNA in breast tumors of Group I, II and III were 0.486, 0.513 and 0.396, respectively. For Group III, PCNA mRNA was significantly less expressed than that in Group I (P=0.023) and II (P=0.005). Relative expression values of PCNA mRNA in axillary lymph nodes of Group I, II and III were 0.541, 0.329 and 0.450, respectively. Compared with Group I, Group III showed a markedly decreased expression of PCNA (P=0.021). The least level of PCNA mRNA was found in Group II, with a significant difference from that in Group HI (P=0.004). Conclusion: Local injection of LADR was an effective therapeutic regimen for lymphatic metastases from breast cancer, regardless of its little effect on primary tumor.

  5. Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat.

    Science.gov (United States)

    Ochodnicky, Peter; Mesarosova, Lucia; Cernecka, Hana; Klimas, Jan; Krenek, Peter; Goris, Maaike; van Dokkum, Richard P E; Henning, Robert H; Kyselovic, Jan

    2014-05-05

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular and structural markers of glomerular and tubulointerstitial renal damage, were studied in a rat model of normotensive nephropathy induced by adriamycin and treated with PPARγ agonist pioglitazone (12mg/kg, po), angiotensin converting enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone had no effect on systolic blood pressure, marginally reduced glycemia and improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone prevented the development of proteinuria and focal glomerulosclerosis to the similar extent as blood-pressure lowering ramipril. Renoprotection provided by either treatment was associated with a reduction in the cortical expression of profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing endothelin-1, and a limitation of interstitial macrophage influx. Treatment with PPARγ agonist, as well as ACE inhibitor comparably affected renal expression of the renin-angiotensin system (RAS) components, normalizing increased renal expression of ACE and enhancing the expression of Mas receptor. Interestingly, combined pioglitazone and ramipril treatment did not provide any additional renoprotection. These results demonstrate that in a nondiabetic renal disease, such as adriamycin-induced nephropathy, PPARγ agonist pioglitazone provides renoprotection to a similar extent as an ACE inhibitor by interfering with the expression of local RAS components and attenuating related profibrotic and inflammatory mechanisms. The combination of the both agents, however, does not lead to any additional renal benefit.

  6. Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy

    OpenAIRE

    Yumei Qi; Huijuan Xiao; Changjie Xu; Xiaojian Tian; Hui Wu; Wei Shen

    2012-01-01

    Cyprinus carpio decoction (CCD) is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR) in rats. 70  eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal g...

  7. Expression of organic cation transporter SLC22A16 in human epithelial ovarian cancer: a possible role of the adriamycin importer.

    Science.gov (United States)

    Ota, Kyoko; Ito, Kiyoshi; Akahira, Jun-ichi; Sato, Naoko; Onogawa, Tohru; Moriya, Takuya; Unno, Michiaki; Abe, Takaaki; Niikura, Hitoshi; Takano, Tadao; Yaegashi, Nobuo

    2007-07-01

    The SLC22A16 is one of the newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is considered to be an active agent for ovarian cancer. Recently, the benefit of adding adriamycin to the current standard regimen, paclitaxel and platinum, is evaluated to improve the outcome of patients with ovarian cancer. Therefore, we examined the expression of SLC22A16 in ovarian cancers. Twelve ovarian carcinoma cell lines were used for immunoblotting and reverse transcription-polymerase chain reaction to confirm the expression of SLC22A16 mRNA and protein. Five normal ovaries, 12 ovarian adenomas, and 94 ovarian cancer cases were obtained from patients after surgical therapy. The specimens were used for immunohistochemistry. The median value of relative SLC22A16 gene expression in cell lines derived from clear-cell adenocarcinoma was significantly higher than that in cell lines from other histologies (P < 0.001). Expression of SLC22A16 protein was also detected in cell lines derived from clear-cell adenocarcinoma. The SLC22A16 immunoreactivity was detected in 15 (16%) of 94 epithelial ovarian cancer, 1 (8.3%) of 12 benign adenomas, but 0 (0%) of 5 normal ovary cases. In ovarian cancer tissues, SLC22A16 immunoreactivity was detected in 2 (5%) of 38 serous adenocarcinoma, 1 (6.7%) of 15 endometrioid adenocarcinoma, 0 (0%) of 14 mucinous adenocarcinoma, and 12 (46.2%) of 26 clear-cell adenocarcinoma (P < 0.0001, clear-cell vs other histologies). In conclusion, SLC22A16 was abundantly expressed in clear-cell adenocarcinoma. Our results suggest that adriamycin-related chemicals that are taken up via SLC22A16 may have the potential to be effective against clear-cell adenocarcinoma.

  8. Application of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia for controlling refractory pain induced by rib metastasis of lung cancer (a STROBE-compliant article)

    Science.gov (United States)

    Xie, Guang-lun; Guo, Da-peng; Li, Zhi-gang; Liu, Chang; Zhang, Wei

    2016-01-01

    Abstract This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy. This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0.5 to 1 mL of adriamycin (0.5%). The conditions of pain and complications were observed before management and 3 days, 1 month, and 3 months after management, respectively. Numerical rating scale (NRS) scores and dosage of morphine were all significantly decreased after management as compared with those before management (all P management as compared with that before management (all P management in nausea and vomiting, and constipation. CT-guided radiofrequency thermocoagulation combined with adriamycin injection in DRG can effectively control lung cancer rib metastasis-related pain which has no response to conventional therapy. This combinatory treatment regimen is featured by better therapeutic effects and a few complications, so it is worthy of being recommended in clinical application. PMID:27749531

  9. Successful management of refractory pleural effusion due to systemic immunoglobulin light chain amyloidosis by vincristine adriamycin dexamethasone chemotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Mima Akira

    2010-10-01

    Full Text Available Abstract Introduction Refractory pleural effusion in systemic immunoglobulin light chain amyloidosis without cardiac decompensation is rarely reported and has a poor prognosis in general (a median survival of 1.6 months. Moreover, the optimum treatment for this condition is still undecided. This is the first report on the successful use of vincristine, adriamycin and dexamethasone chemotherapy for refractory pleural effusion due to systemic immunoglobulin light chain amyloidosis without cardiac decompensation. Case presentation We report the case of a 68-year old Japanese male with systemic immunoglobulin light chain amyloidosis presenting with bilateral pleural effusion (more severe on the right side in the absence of cardiac decompensation that was refractory to diuretic therapy. The patient was admitted for fatigue, exertional dyspnea, and bilateral lower extremity edema. He had been receiving intermittent melphalan and prednisone chemotherapy for seven years. One month before admission, his dyspnea had got worse, and his chest radiograph showed bilateral pleural effusion; the pleural effusion was ascertained to be a transudate. The conventionally used therapeutic measures, including diuretics and thoracocentesis, failed to control pleural effusion. Administration of vincristine, adriamycin, and dexamethasone chemotherapy led to successful resolution of the effusion. Conclusion Treatment with vincristine, adriamycin, and dexamethasone chemotherapy was effective for the refractory pleural effusion in systemic immunoglobulin light chain amyloidosis without cardiac decompensation and appears to be associated with improvement in our patient's prognosis.

  10. [Vincristine, adriamycin, mitomycin-C and UFT (VAM-UFT) therapy in progressive or recurrent breast cancer].

    Science.gov (United States)

    Yasutake, K; Imamura, Y; Yoshimura, Y; Oya, M; Matsushita, K; Hozumi, T; Katou, J; Okutani, T; Irie, K

    1989-07-01

    Since June 1984, 23 cases of progressive or recurrent breast cancers were treated with combination chemotherapy of VAM-UFT consisting of vincristine, adriamycin, mitomycin C and UFT. Clinical effects of VAM-UFT therapy were 3 CR, 12 PR, and the response rate was 65.2%. Its effective interval was 3 months. But the patients treated with over 4 cycles of VAM-UFT therapy showed an 85% response rate, with a 5-month effective interval. In each patient's background, a shorter disease free interval tended to be more highly effective, but other factors were not significant. Scirrhous carcinoma of pathology evidenced slightly high response rate. Compared with the survival time of patients treated with under 3 cycles and over 4 cycles of this therapy, the latter was significantly longer. Toxicity involved leukocytopenia (74%), thrombocytopenia (22%), anemia (30%), alopecia (91%), nausea and vomiting (87%) and stomatitis (35%), but cases in which the treatment was stopped were not observed. Therefore VAM-UFT therapy had a highly therapeutic effect, reflected in an 85% response rate, for progressive or recurrent breast cancers.

  11. Evaluating the antitumor activity of combined photochemotherapy mediated by a meso-substituted tetracationic porphyrin and adriamycin

    Institute of Scientific and Technical Information of China (English)

    Kawser Kassab

    2009-01-01

    The combined anticancer modality comprising por-phyrins as photodynamic sensitizers and anticancer drugs has been an interesting subject for many researchers. In this study, the photochemotherapeutic effect mediated by simultaneous photoactivation of tet-racationic meso-tetrakis(N-methyl-4-pyridyl) porphine tetratosylate (TMPyP) and adriamycin (ADM) were explored using human hepatocellular carcinoma cell line (HePG2). The efficiency of TMPyP acting in concert with ADM in the dark and in the presence of photoirradiation was evaluated, by studying cell viabi-lity, caspase-3 activity and ultrastructurai changes in the cells after incubation with each of the two agents,separately, or simultaneously as a co-mixture. Under dark conditions, the simultaneous incubation of cells with TMPyP and ADM significantly enhanced cell death by 1.8 folds and 1.3 folds, compared with TMPyP or ADM treatment, respectively. After photoir-radiation, the antiproliferative effect of the co-treatment with TMPyP and ADM increased further by 2 folds.Transmission electron microscopy and the measure-ments of caspase-3 levels in treated cells revealed that the co-treatment of cells with ADM and TMPyP fol-lowed by light irradiation directed the cell death towards necrosis and abrogated the apoptotic cell death pathway, which was exhibited in cells treated with ADM in absence and in presence of photoirradiation.

  12. The effect of oxidized low-density lipoprotein combined with adriamycin on the proliferation of Eca-109 cell line

    Directory of Open Access Journals (Sweden)

    Cui Jia

    2011-06-01

    Full Text Available Abstract Background The purpose of this study was to identify the affect on the proliferation Eca-109 cells treated with oxidized low-density lipoprotein (ox-LDL combined with adriamycin (ADM. Methods Eca-109 cell were cultured in the presence of oxLDL/ADM, and cell proliferation tested by MTT and cell apoptosis was monitored by the proportion of apoptosis and cell cycle by flow cytomester. We simultaneously evaluated the level of associated- apoptosis Bcl-2, Bax, and Caspase-3 gene mRNA and protein. Results OxLDL were cytotoxic and activate apoptosis. OxLDL combined with ADM significant enhanced the proportion rate of apoptosis on a time and dose dependency. The expressions of the inhibiting apoptosis Bcl-2 gene mRNA and protein were down regulated, whereas, the expressions of the promoting apoptosis Bax, and Caspase-3 genes mRNA and protein were up regulation. Conclusion These results suggested that oxLDL have cytotoxicity and activate apoptosis on the Eca-109 cells. OxLDL combined with ADM have a synergistic effect on the apoptosis induced Eca-109 cells. Furthermore, oxLDL may contribute to the improvement of clinical chemotherapy of cancer need to make further investigation.

  13. Combination of Human Fas (CD95/Apo-1) Ligand with Adriamycin Significantly Enhances the Efficacy of Antitumor Response

    Institute of Scientific and Technical Information of China (English)

    Zhongchen Liu; Ruizhen Liu; Jinhua Qiu; Ping Yin; Fanghong Luo; Jinhua SU; Wenzhu Li; Caixia Chen; Xin Fan; Jiakai Zhang; Guohong Zhuang

    2009-01-01

    The prognosis of hepatocellular carcinoma (HCC) is poor, even with the combined treatment of curative resection and adjuvant chemoradiotherapy. To solve this problem, many biologic therapies have been investigated. Fas ligand (FasL, CD95L) is mainly expressed in activated T lymphocytes and natural killer (NK) cells, and plays a central role in both cell-mediated immunity and immune downregnlation. Several studies have shown that FasL is expressed in HCC. In the present report, we prepared recombinant human pET-22b(+)/FasL protein and investigated the effect of FasL on HCC cells in vitro and on tumor growth in a murine HCC tumor model. The well-known cytotoxic chemotherapeutic reagent adriamycin (ADM) served as a control. We found that FasL effectively suppressed the viability of H22 tumor cells and significantly induced the apoptosis of H22 cells. The apoptotic levels of cells treated with FasL-ADM were significantly higher than those treated with FasL or ADM alone, and the FasL-ADM combination resulted in a more than additive effect on tumor growth delay in this model. The results suggested that combined treatment of FasL and other chemotherapeutic agents 5 be a new approach to improve the efficacy of chemotherapy for HCC. Cellular & Molecular Immunology. 2009;6(3):167-174.

  14. miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27(kip1) pathway.

    Science.gov (United States)

    Wang, Dan-Dan; Yang, Su-Jin; Chen, Xiu; Shen, Hong-Yu; Luo, Long-Ji; Zhang, Xiao-Hui; Zhong, Shan-Liang; Zhao, Jian-Hua; Tang, Jin-Hai

    2016-11-01

    The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. Since miR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer through PTEN/Akt/p27 (kip1) pathway. Firstly, in vivo, we verified that miR-222 was upregulated in chemoresistant tissues after surgery compared with the paired preneoadjuvant samples of 21 breast cancer patients. Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to validate the pathway from the parental sensitive cell line (MCF-7/S). MCF-7/Adr and MCF-7/S were transfected with miR-222 mimics, miR-222 inhibitors, or their negative controls, respectively. The results showed that inhibition of miR-222 in MCF-7/Adr significantly increased the expressions of PTEN and p27 (kip1) and decreased phospho-Akt (p-Akt) both in mRNA and protein levels (p cancer cells to Adr through PTEN/Akt/p27 (kip1) signaling pathway, which provided a potential target to increase the sensitivity to Adr in breast cancer treatment and further improved the prognosis of breast cancer patients.

  15. Pharmacokinetic analysis of adriamycin (doxorubicin and related fluorescent compounds in Ehrlich tumor-bearing mouse plasma and tissues.

    Directory of Open Access Journals (Sweden)

    Shinozawa,Shinya

    1982-04-01

    Full Text Available Pharmacokinetic analysis of the distribution and concentration of adriamycin (ADM in mouse plasma and tissues was carried out by differentiating the unmetabolized form from metabolized ones using high-performance liquid chromatography after a single intravenous injection. Marked differences between ADM and total ADM equivalent values (total ADM values or its metabolized forms were observed in the pharmacokinetic behavior in plasma and tissue distributions. The ratios of tissue per plasma for total ADM and for ADM values in the liver, kidney and heart showed a two-digit magnitude each time they were examined. Twenty four h later, the ratios for ADM values in the liver, kidney, heart and lung were at high levels; 43.1, 48.1, 57.9 and 45.5 times, respectively. Twenty min after injection the ratios for total ADM values in the spleen, lung and tumors were comparatively small, but 24 h later, the ratio had increased 36.5, 45.5 and 6.8 times respectively.

  16. Angiotensin Ⅱ suppresses adriamycin-induced apoptosis through activation of phosphatidylinositol 3-kinase/Akt signaling in human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yanbin Zhao; Xuesong Chen; Li Cai; Yanmei Yang; Guangjie Sui; Jin Wu

    2008-01-01

    Angiotensin Ⅱ (Ang Ⅱ) stimulates tumor growth and angiogenesis in some solid cancer cells, but its anti-apoptosis role in breast cancer remains unclear. To address this issue, we investigated the effect of Ang Ⅱ on adriamycin-induced apoptosis in breast cancer MCF-7 cells. Treatment of human breast cancer MCF-7 cells with adriamycin, a DNA topoisomerase Hα inhibitor, caused apoptosis. However, cells pretreated with Ang Ⅱ were resistant to this apoptosis. Ang Ⅱ significantly reduced the ratio of apoptotic cells and stimulation of phospho-Akt-Thr308 and phospho-Akt-Ser473 in a dose-dependent and time-dependent manner. In addition, Ang Ⅱ significantly prevented apoptosis through inhibiting the cleavage of procaspase-9, a major downstream effector of Akt.The Ang Ⅱ type 1 receptor (AT1R) was responsible for these effects. Among the signaling molecules downstream of AT1R,we revealed that the phosphatidylinositol 3-kinase/Akt pathway plays a predominant role in the anti-apoptotic effect of Ang Ⅱ. Our data indicated that Ang Ⅱ plays a critical antiapoptotic role in breast cancer cells by a mechanism involving AT1R/phosphatidylinositol 3-kinase/Akt activation and the subsequent suppression of caspase-9 activation.

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

    Directory of Open Access Journals (Sweden)

    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

  18. Remarkable Response to Neoadjuvant Therapy with Methotrexate, Vinblastine, Adriamycin, and Cisplatin for Undifferentiated Bladder Carcinoma: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Kenji Numahata

    2014-11-01

    Full Text Available We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.

  19. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor...... efficacy was found to be significantly higher (~1.76- and ~4.5-fold) for the combination as compared to Dox-LCNPs (per oral) and Adriamycin (i.v.) respectively. Notably, level of residual tumor burden was insignificant (P>0.05) after 30days in case of combination and LipoDox® (i.v.). Interestingly......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

  20. 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.

  1. 阿霉素自组装纳米粒的制备及其抗肿瘤活性的研究%Preparation and Research on the Aniti-Tumor Activity of Adriamycin Self-assembled Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    诸佳珍; 李范珠

    2013-01-01

    [目的]制备胆固醇基普鲁兰多糖阿霉素自组装纳米粒(Self-assembled ADM-loaded cholesterol modified pul ulan nanoparticles, ADM-CHSP-SAN)并考察其体外抗肿瘤活性。[方法]以胆固醇基普鲁兰多糖(cholesterol-modified pul ulan,CHSP)为载体,采用透析法制备ADM-CHSP-SAN,并测定其形态、粒径、Zeta电位、包封率和载药量,采用MTT法研究其抑制U251肿瘤细胞的活性作用。[结果]ADM-CHSP-SAN外观呈圆形或类圆形,平均粒径为(112.8±1.02)nm,Zeta电位为(-27.2±0.246)mV,包封率和载药量分别为(67.14±1.21)%和(7.65±0.58)%;体外释药行为符合Higuchi方程;给药剂量大于25μg·mL-1时,ADM-CHSP-SAN抑制U251肿瘤细胞的活性作用明显优于阿霉素溶液剂(P<0.01)。[结论]将阿霉素制备成ADM-CHSP-SAN可有效提高药物的抗肿瘤活性。%[Objective] To prepare adriamycin self-assembled nanoparticles, and study the in vivo anti-tumor activity. [Methods]The self-assembled adri-amycin loaded cholesterol-modified pul ulan nanoparticles were prepared by dialysis and were characterized by morphology for particle size,Zeta potential, entrapment efficiency,drug loading content.They were incubated with U251 cel s to assess the inhibition ability of the self-assembled adriamycin-loaded cholesterol-modified pul ulan nanoparticles. [Results]The morphology of self-assembled adriamycin loaded cholesterol-modified pul ulan nanoparticles was spherical. The mean particle size, Zeta potential, entrapment efficiency and drug loading were (112.8 ±1.02)nm,(-27.2±0.246)mV,(67.14±1.21)% and (7.65±0.58)%, respectively.The profiles of release were expressed wel by Higuchi equation. When the dosages were 25μg·mL-1 plus, the inhibiton ability against U251 was stronger than adriamycin solution( P<0.01).[Conclusion]The self-assembled adriamycin loaded cholesterol-modified pul ulan nanoparticles exhibited more cycitoxic activity against U251

  2. The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity.

    Science.gov (United States)

    Taskin, Eylem; Ozdogan, Kalender; Kunduz Kindap, Elvan; Dursun, Nurcan

    2014-05-01

    Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (pinduced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo.

  3. A Redox-Sensitive Micelle-Like Nanoparticle Self-Assembled from Amphiphilic Adriamycin-Human Serum Albumin Conjugates for Tumor Targeted Therapy

    Science.gov (United States)

    Chen, Lin; Chen, Feng; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Yu, Jiangming; Yan, Zhiqiang; Zhang, Fulei; Sun, Yun; Chen, Di; Jiang, Cheng; Zhao, Xianxian; Gao, Yong; Guo, Shangjing; Li, Wei

    2015-01-01

    The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited by its side effects like high toxicity and insolubility. Nanomedicine offers new hope for overcoming the shortcomings. But how to increase in vivo stability and to control intracellular drug release is a key issue for nano-based formulations. Herein, the hydrophobic ADR was successfully linked to the biocompatible human serum albumin (HSA) by disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR. The novel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stable core shell structure with glutathione (GSH) sensitive linkers. The stable PDPH linkers at extracellular level were broken by GSH at intracellular level with a controlled ADR release profile. The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviously enhanced by such redox-sensitive ADR-HSA NPs. Additionally, as observed by IVIS Lumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs was much higher than that of HSA/ADR NPs due to its high stability. Consequently, the in vivo tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing gastric tumors. These in vitro/vivo results indicated that disulfide-bond-containing ADR-HSA NPs were an effective nanodrug delivery system for cancer therapy. PMID:26075280

  4. Tumor endothelial expression of P-glycoprotein upon microvesicular transfer of TrpC5 derived from adriamycin-resistant breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, YePing; Pan, QiongXi; Jiang, Li; Chen, Zhen; Zhang, FangFang; Liu, YanJun; Xing, Hui; Shi, Mei; Li, Jiao; Li, XiYuan; Zhu, YaoDan; Chen, Yun; Bruce, Iain C.; Jin, Jian, E-mail: jinjian31@126.com; Ma, Xin, E-mail: maxin@jiangnan.edu.cn

    2014-03-28

    Highlights: • TrpC5 was mainly accumulated in microvesicles of drug-resistant MCF-7/ADM cells. • Microvesicles from MCF-7/ADM transferred TrpC5 to endothelial cells. • TrpC5 inhibition reduced P-glycoprotein accumulation on tumor blood vessels in vivo. - Abstract: Treatment of carcinoma commonly fails due to chemoresistance. Studies have shown that endothelial cells acquire resistance via the tumor microenvironment. Microvesicle (MV) shedding from the cell membrane to the microenvironment plays an important role in communication between cells. The aim of the present study was to determine whether MCF-7 adriamycin-resistant cells (MCF-7/ADM) shed MVs that alter the characteristics of human microvessel endothelial cells (HMECs). MVs from tumor cells transferred a Ca{sup 2+}-permeable channel TrpC5 to HMECs, inducing the expression of P-glycoprotein (P-gp) by activation of the transcription factor NFATc3 (nuclear factor of activated T cells isoform c3). Expression of the mdr1 gene was blocked by the TrpC5-blocking antibody T5E3, and the production of P-gp in HMECs was reduced by blockade of TrpC5. Thus, we postulate that endothelial cells acquire the resistant protein upon exposure to TrpC5-containg MVs in the microenvironment, and express P-gp in the TrpC5–NFATc3 signal pathway.

  5. Distribution and antitumor activity of adriamycin given in a high-dose and a repeated low-dose schedule to mice.

    Science.gov (United States)

    Pacciarini, M A; Barbieri, B; Colombo, T; Broggini, M; Garattini, S; Donelli, M G

    1978-05-01

    Experimental studies on the distribution of adriamycin (AM) under different treatment conditions and possible correlations between tissue and plasma levels and chemotherapeutic activity are discussed. C57BL/6J mice bearing im Lewis lung carcinoma and (C3H x O2O)F1 mice bearing mammary carcinoma were injected iv with AM at a single dose of 15 mg/kg or with the same total amount of drug administered in spaced doses of 3.75 mg/kg for 4 consecutive days. In the two experimental systems studied, the drug reached approximately the same value in the tumor and spleen with both types of treatment, but with the 3.75-mg/kg x 4 schedule much lower AM concentrations were observed in the heart than with the single high-dose treatment. The therapeutic activity of the two treatments also differed: the antitumor and antimetastatic effect was the same in the two tumor systems, but with the 3.75-mg/kg x 4 schedule, increased survival and somewhat lower toxicity were observed. Daunorubicin, tested in the mammary carcinoma system with the two schedules of treatment, behaves very similarly to AM in terms of both distribution and chemotherapeutic effect.

  6. Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy.

    Science.gov (United States)

    Scarfe, Lauren; Rak-Raszewska, Aleksandra; Geraci, Stefania; Darssan, Darsy; Sharkey, Jack; Huang, Jiaguo; Burton, Neal C; Mason, David; Ranjzad, Parisa; Kenny, Simon; Gretz, Norbert; Lévy, Raphaël; Kevin Park, B; García-Fiñana, Marta; Woolf, Adrian S; Murray, Patricia; Wilm, Bettina

    2015-09-02

    Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers.

  7. Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Yumei Qi

    2012-01-01

    Full Text Available Cyprinus carpio decoction (CCD is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR in rats. 70  eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal group received 6.5 mg/kg⋅bw of ADR injection into the vena caudalis once. Different doses of CCD (11.3 and 22.5 g kg-1 were lavaged to rats in YD and YG groups, respectively. Then the serum biochemical values of the total protein (TP, albumin (ALB, blood urea nitrogen (BUN, creatinine (Cr, electrolyte levels, and the urinary protein (UP content in 12 hr urine were measured. Interleukin-4 (IL-4 and interferon (INF-γ were measured by enzyme-like immunosorbent assay (ELISA. The pathomorphological analysis was observed using light and electron microscopy, and the expressions of nephrin and CD2-associated protein (CD2AP in renal tissues were determined by immunohistochemical assay. The results indicated that CCD can relieve ADR-induced nephropathy (ADN by improving the nutrition status, regulating the immunity, and inhibiting proteinuria by increasing nephrin and CD2AP expressions.

  8. STAT3 contributes to NK cell recognition by modulating expression of NKG2D ligands in adriamycin-resistant K562/AO2 cells.

    Science.gov (United States)

    Cai, Xiaohui; Lu, Xuzhang; Jia, Zhuxia; Zhang, Xiuwen; Han, Wenmin; Rong, Xiao; Ma, Lingdi; Zhou, Min; Chen, Baoan

    2015-11-01

    Leukemic cells can survive after chemotherapy by acquisition of multidrug resistance genes, but other phenotypes related to escape from immune recognition remain elusive. Adriamycin-resistant K562/AO2 cells are less susceptible to elimination by NK cells compared with wild type K562 cells due to lower expression of NKG2D ligands. Treatment of K562/AO2 cells with STAT3 inhibitor VII resulted in reduced expression of multidrug resistance gene P-glycoprotein, and up-regulation of NKG2D ligands on K562/AO2 cells. Meanwhile, K562/AO2 cells treated with STAT3 inhibitor proliferated less and were more susceptible to killing by NK cells than untreated K562/AO2 cells. The enhanced cytotoxicity of NK cells against K562/AO2 cells was partly blocked by treatment of NK cells with anti-NKG2D antibodies. These data suggest that STAT3 contributes to NK cell recognition by modulating NKG2D ligands in K562/AO2 cells, which may a mechanism by which cells survive and cause relapse of leukemia.

  9. 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.

  10. 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.

  11. The Fanconi anemia/BRCA pathway is involved in DNA interstrand cross-link repair of adriamycin-resistant leukemia cells.

    Science.gov (United States)

    Yao, Chenjiao; Du, Wei; Chen, Haibing; Xiao, Sheng; Huang, Lihua; Chen, Fangping

    2015-03-01

    The Fanconi anemia/BRCA (FA/BRCA) pathway plays a vital role in DNA damage repair induced by DNA cross-linking agents and is closely related to drug response in cancer treatment. Here we demonstrate that the FA/BRCA pathway contributes to acquired drug resistance in adriamycin (ADR)-resistant leukemia cell lines, and disruption of this pathway partially reverses the drug resistance. We observed that ADR-resistant cells have reduced DNA interstrand cross-links (ICL) compared with ADR-sensitive cells. Western blot studies demonstrated enhanced FA protein expression in ADR-resistant cells. Using siRNA to knock down FANCF in K562/R drug-resistant cells showed increases in sensitivity to ADR and ADR-induced DNA damage, and demonstrated a direct relationship between the FA/BRCA pathway and drug sensitivity. Overexpression of FANCF in K562 drug-sensitive cells partially reproduced the drug-resistant phenotype. These results show that the FA/BRCA pathway is involved in acquired ADR resistance of leukemia cells. The FA/BRCA pathway may be a new target to reverse ADR resistance in leukemia treatment.

  12. 阿霉素热化疗对肝癌细胞增殖和凋亡的影响%Proliferation and apoptosis induced by thermochemotherapy of adriamycin( ADM) in hepatocellular carcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    王倩荣; 史正华; 马骥; 刘文超

    2011-01-01

    Objective:To observe the effect of thermotherapy combined with adriamycin on cell proliferation and apoptosis of hepatocellular carcinoma cells. Methods: The working concentration of adriamycin was determined by MTT assay. Cells were suhjected to thermotherapy ( at 43℃ ) and chemotherapy with adriamycin alone or in conjunction , and the cell survival rates were determined at 24h after the treatment. The cell growth inhihition effect was evaluated by MTT assay,and the apoptosis rates of HepG2 and HHCC were determined by flow cytometric analyses. Results : The IC50 of adriamycin was defined as its working concentration. The thermotherapy at 43℃ for 60 min in combination with chemotherapy significantly inhibited the growth of hoth HepG2 and HHCC cells. The results of flow cytometry analyses showed that thermotherapy and adriamycin chemotherapy, used either alone or in combination, obviously increased the apoptosis rates of HHCC and HepG2 cells( P < 0. 05 ). Conclusion : Adriamycin combined with thermotherapy for 60min can increase the inhibition of proliferation and the apoptosis rates of HepG2 and HHCC cells.%目的:探讨阿霉素(ADM)加热化疗对人肝癌细胞HHCC及HepG2的增殖抑制和凋亡诱导作用.方法:以体外培养的人肝癌细胞HHCC和HepG2为研究对象,采用水浴加温法,观察单纯热疗,ADM化疗和热化疗对细胞增殖和凋亡的影响.MTT法确定阿霉素的工作浓度并检测细胞增殖的抑制作用,流式细胞术检测细胞凋亡.结果:热化疗组细胞的抑制率显著高于单纯热疗、单纯化疗组[HHCC细胞:(65.77±2.54)% vs (23.18±0.81)%、(38.35±2.23)%,P<0.05.HepG2细胞:(74.25±1.53 )% vs (17.12±2.86)%、( 30.35±5.90)%,P<0.05].热化疗组细胞凋亡率显著高于单纯热疗组、单纯化疗组[HHCC细胞:(76.1±2.33)% vs (23.83±1.76)%、(45.57±2.81 )%,P<0.05.HepG2细胞:(76.9±2.79)%vs (19.7±7.63 )%、(37.43±1.88)%,P<0.05].结论:加热能增强ADM对HHCC及HepG2的增殖抑制和诱导凋亡作用.

  13. 壳寡糖-聚乳酸阿霉素胶团体外缓释性能考察%Evaluation of Delayed Release Efficiency in Vitro of Adriamycin Chitosan-Polylactic Acid Polymeric Micelles

    Institute of Scientific and Technical Information of China (English)

    隋璐莹

    2015-01-01

    Objective Evaluate the ef iciency of delayed release in vitro of adriamycin chitosan-polylactic acid polymeric micel es.Methods Hypersound dispersion method to prepare the polymeric micel es. Adriamycin as a model drug was then incorporated into the micel es by dialysis. Evaluate the ef iciency of delayed release of adriamycin chitosan-polylactic acid polymeric micel es by in vitro investigation. Results The CSO-PLA micel es with 5000 molecule weight of PLA loading Adr displayed more sustained-release characteristic.Conclusion The micel es loading Adr displayed sustained-release characteristic in vitro. The CSO-PLA (PLA with molecule weight 5000) micel es loading Adr displayed significant sustained-release characteristic.%目的:考察阿霉素壳寡糖-聚乳酸嫁接物胶团的缓释性能。方法以超声分散法制备嫁接物胶团;以阿霉素为模型药物,透析法制备载药胶团。进行载药胶团体外释放实验,考察壳寡糖-聚乳酸共聚物胶团的缓释性能。结果在壳寡糖-聚乳酸嫁接物中,聚乳酸分子量为5000的两种壳寡糖-聚乳酸嫁接物载药胶团体外释放缓释效果明显。结论壳寡糖-聚乳酸聚合物胶团具有显著的缓释特征。其中聚乳酸分子量为5000的壳寡糖-聚乳酸嫁接物,缓释效果更明显。

  14. Regulation of angiotensin-(1-7) and angiotensin Ⅱ type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

    Institute of Scientific and Technical Information of China (English)

    Wen-na ZONG; Xin-zheng LU; Xiao-hui YANG; Xiu-mei CHEN; Hong-juan HUANG; Hong-jian ZHENG; Xiao-yi QIN; Yong-hong YONG; Ke-jiang CAO; Jun HUANG

    2011-01-01

    Aim:To investigate the possible effects of telmisartan and losartan on cardiac function in adriamycin (ADR)-induced heart failure in rats,and to explore the changes in plasma level of angiotensin-(1-7)[Ang-(1-7)] and myocardial expression of angiotensin Ⅱ type 1/2 receptors (AT1R / AT2R) and Mas receptor caused by the two drugs.Methods:Male Sprague-Dawley rats were randomly divided into 4 groups:the control group,ADR-treated heart failure group (ADR-HF),telmisartan plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR).ADR was administrated (2.5 mg/kg,ip,6 times in 2 weeks).The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (30 mg/kg daily),respectively,for 6 weeks.The plasma level of Ang-(1-7) was determined using ELISA.The mRNA and protein expression of myocardial Mas receptor,AT1R and AT2R were measured using RT-PCR and Western blotting,respectively.Results:ADR significantly reduced the plasma level of Ang-(1-7) and the expression of myocardial Mas receptor and myocardial AT2R,while significantly increased the expression of myocardial AT1R.Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and suppressed myocardial AT1R expression,but did not influence the expression of Mas receptor and AT2R.Conclusion:The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1-7) and myocardial AT1R expression.

  15. Beneficial effects of the activation of the angiotensin-(1-7) MAS receptor in a murine model of adriamycin-induced nephropathy.

    Science.gov (United States)

    Silveira, Kátia Daniela; Barroso, Lívia Corrêa; Vieira, Angélica Thomáz; Cisalpino, Daniel; Lima, Cristiano Xavier; Bader, Michael; Arantes, Rosa Maria Esteves; Dos Santos, Robson Augusto Souza; Simões-E-Silva, Ana Cristina; Teixeira, Mauro Martins

    2013-01-01

    Angiotensin-(1-7) [Ang-(1-7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-β. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas(+/+) ) and Mas knockout (Mas (-/-)) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas(+/+) , but not in Mas (-/-) mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1-7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies.

  16. 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.

  17. A comparison of the long-term effects of lanthanum carbonate and calcium carbonate on the course of chronic renal failure in rats with adriamycin-induced nephropathy.

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Takashima

    Full Text Available Lanthanum carbonate (LA is an effective phosphate binder. Previous study showed the phosphate-binding potency of LA was twice that of calcium carbonate (CA. No study in which LA and CA were given at an equivalent phosphate-binding potency to rats or humans with chronic renal failure for a long period has been reported to date. The objective of this study was to compare the phosphate level in serum and urine and suppression of renal deterioration during long-term LA and CA treatment when they were given at an equivalent phosphate-binding potency in rats with adriamycin (ADR-induced nephropathy. Rats were divided into three groups: an untreated group (ADR group, a CA-treated (ADR-CA group and a LA-treated (ADR-LA group. The daily oral dose of LA was 1.0 g/kg/day and CA was 2.0 g/kg/day for 24 weeks. The serum phosphate was lower in the ADR-CA or ADR-LA group than in the ADR group and significantly lower in the ADR-CA group than in the ADR group at each point, but there were no significant differences between the ADR and ADR-LA groups. The serum phosphate was also lower in the ADR-CA group than in the ADR-LA group, and there was significant difference at week 8. The urinary phosphate was significantly lower in the ADR-CA group than in the ADR or ADR-LA group at each point. The urinary phosphate was also lower in the ADR-LA group than in the ADR group at each point, and significant difference at week 8. There were no significant differences in the serum creatinine or blood urea nitrogen among the three groups. In conclusion, this study indicated the phosphate-binding potency of LA isn't twice as strong as CA, and neither LA nor CA suppressed the progression of chronic renal failure in the serum creatinine and blood urea nitrogen, compared to the untreated group.

  18. 半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药物动力学研究%Pharmacokinetic analysis of galactosylated albumin magnetive Adriamycin nanoparticle(GAMAN) in home rabbits

    Institute of Scientific and Technical Information of China (English)

    张阳德; 王荣兵; 龚连生; 席浩; 刘勤

    2004-01-01

    目的对家兔一次性颈静脉给药,检测自制药物与普通阿霉素在药动力学方面有无差异及了解新药的药动学特点.方法家兔12只,随机分为两组,每组6只,均予颈静脉置管、注射、抽血,一组按3.0mg/kg给予阿霉素;一组按63.2 mg/kg给予半乳糖化白蛋白磁性阿霉素纳米粒,每次抽血1ml,分离血清低温保存,以氯仿-甲醇液萃取阿霉素,在高效液相色谱仪下检测色谱峰高.根据阿霉素标准曲线求血清中阿霉素浓度.以"3P87"进行药动学分析.结果阿霉素与半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药动学规律符合三室开放模型;与阿霉素相比,实验组药物的消除相半衰期延长了1.9~3.2倍,清除率是阿霉素的0.5369倍;血药浓度-时间曲线下面积(AUC)是阿霉素的1.3697倍.结论阿霉素经过与白蛋白、磁性微粒结合,并以半乳糖修饰,改变了原药的体内分布特性,延长了药物半衰期,增加了靶器官肝脏的药物浓度.%Objective: Through one-off jugular vein injection on home rabbits with different two drugs, to check up whether the pharmacokinetic of galactosylated albumin magnetive Adriamycin naroparticle (GAMAN)was different to the Adriamycin, and to find out the pharmacokinetic characteristics of the GAMAN. Methods:The twelve home rabbits were divided into two groups in random six in each. Every rabbit was put a pipe in its jugular vein, then injected drugs and phlebotomized. One group was given Adriamycin 3 mg/kg to every rabbit, the other group was given GAMAN 63.2 mg/kg equivalent to Adfiamycin 3 mg/kg to every rabbit. Phlebotomized 1 ml each time, then separated serum and saved 0.3 ml at low temperature, extracted the Adriamycin with chloroform-carbinol, put it under the High Performance Liquid Chromatography (HPLC) to examine the special chromatogram peak value ratio. Finally, the concentration of the Adriamycin in serum was accounted according to the standard curve of

  19. Effect of Oleanolic Acid on Adriamycin Induced Apoptosis of Cultured Human Skin Keratinocytes in Vitro%齐墩果酸对阿霉素诱导的培养人皮肤角质形成细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    张兴洪; 刘彦群; 魏志平; 田美华

    2011-01-01

    Objective To investigate the effect of oleanolic acid (OA) on adriamycin induced apoptosis of cultured human skin keratinocytes in vitro. Methods Human skin keratinocytes were cultured with different concentrations of oleanolic acid and adriamycin. Absorbance A was detected by colorimetric assay of MTT. The optical density (OD) values were showed on a scanning multiwell spectrophotometer. Apoptosis rate of human skin keratinocytes was detected by flow cytometry. Results We found that the proliferation of human skin keratinocytes was inhibited by adriamycin. If cells were pre-incubated with oleanolic acid, OD value was significantly higher and apoptosis induced by adriamycin was suppressed (P<0.05). Conclusion This study suggests that oleanolic acid could partially inhibit adriamycin induced apoptosis of cultured human skin keratinocytes.%目的 探讨齐墩果酸对阿霉素诱导的培养人皮肤角质形成细胞凋亡的影响.方法 用MTT法通过比色分析测定吸光度(A)值,检测不同剂量齐墩果酸和阿霉素给药对角质形成细胞增殖的影响,用流式细胞仪检测细胞凋亡.结果 阿霉素抑制体外培养的人皮肤角质形成细胞增殖,先给予齐墩果酸处理细胞,然后给予阿霉素,齐墩果酸升高A值(P<0.05),降低细胞凋亡率(P<0.05).结论 先行给予适当剂量齐墩果酸处理细胞,能一定程度减轻阿霉素对细胞的损伤,表现出对阿霉素致凋亡的保护作用.

  20. 阿霉素诱导扩张型心肌病大鼠心功能的变化%The Changes of Cardiac Function in Rats with Adriamycin-induced Dilated Cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    李倩晓; 那荣妹; 李晓菲; 刘百亭; 于勤

    2013-01-01

    Objective:To investigate the changes of cardiac function in rats with adriamycin-induced dilated cardiomyopathy.Method:85 male SD rats(SPF degree,weighing 240-290 g,8 weeks old)were divided into 2 groups:DCM group(n=65),normal control group(n=20). The rats of DCM group were given intraperitoneal injection of adriamycin(2.5 mg/kg every time,one time every week for 6 weeks,total dose:15 mg/kg);the rats of normal control group were given the same injection volume of normal saline instead of adriamycin intraperitoneal injection. In the 10th week after intraperitoneal injection,the two groups of rats underwent echocardiography for left ventricular end-diastolic diameter,left ventricular end-systolic diameter,left ventricular ejection fraction and left ventricular fractional shortening. Result:Cardiac ultrasound examination showed that expanded heart chamber and diffuse weakening of the wall activity of DCM group of rats. Their left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly larger than normal control group(P<0.05),while left ventricular ejection fraction and left ventricular fractional shortening were significantly lower than normal control group(P<0.05). Conclusion:Intraperitoneal injection of adriamycin induced DCM rats cardiac function decline.%目的:通过腹腔注射阿霉素诱导制备扩张型心肌病(dilated cardiomyopathy,DCM)大鼠模型,探讨其心功能的变化。方法:选取体质量为240~290 g的8周龄、SPF级近交系雄性SD大鼠85只,分为2组:DCM组(n=65)、正常对照组(n=20)。DCM组采用腹腔注射阿霉素的方法构建DCM模型;正常对照组则注射等容积的生理盐水。给药第10周对两组大鼠行心脏超声检查,观察左室舒张末期内径、左室收缩末期内径、左室射血分数、左室短轴缩短率。结果:心脏超声检查显示DCM组大鼠心腔扩大,室壁活动度弥漫性减弱,左室舒

  1. Establishment and evaluation of adriamycin-induced chronic heart failure model in SD rats%SD大鼠阿霉素慢性心力衰竭模型的建立与评价

    Institute of Scientific and Technical Information of China (English)

    吴运香; 张野; 谢春林; 张书杰; 解翔; 姜凡; 陈志武

    2011-01-01

    Aim To establish and evaluate an adriamycin-induced chronic heart failure model by tail vein injection in Sprague Dawley ( SD ) rats. Methods Adult male SD rats were randomly divided into two groups : the control group ( CON,n = 8 ) and the adriamycin-induced heart failure group ( ADR,n = 20 ).All rats in ADR group received 2 mg · kg-1adriamycin as an intravenous tail vein infusion once a week for 6 weeks at a total dose of 12 mg · kg-1 ; meanwhile in CON group, rats received an equal volume of 0. 9% sodium chloride intravenously. Transthoracic: echocardiography was performed to observe cardiac function including left ventricular end-diastolic diameter( LVEDD ) and end-systolic diameter ( LVESD ) and calculate left ventricular fractional shortening ( LVFS ) and ejection fraction ( LVEF ) 2 weeks later after the last injection. The pathological c:hange was analyzed by HE and Van Gieson ( VG ) stain. The plasma concentration of brain natriuretic peptide ( BNP ) was determined by euzymelinked immunosorbent assay ( ELISA ). Results Compared with CON group, LVEDD and LVESD were increased in ADR group, and LVFS and LVEF were significantly decreased ( P < 0. 01 ). The pathological changes by HE stain in ADR group were part of myocardial fiber fracture and myocardial periacardial inflammatory infiltration. Collagen volume fraction ( CVF ) and perivascular circumferential collagen area ( PVCA )by VG stain were significantly higher( P < 0. 01 ) than CON group. And the level of plasma BNP was significantly higher than that in CON group. Conclusions Adriamycin at a multiple intravenous dose of 2. 0 mg · kg-1 can be used to establish a reliable model of non-ischemia chronic heart failure in SD rats and lead to a decline in ventricular function and pathological changes.%目的 通过尾静脉注射阿霉素建立SD大鼠慢性心力衰竭模型,并对其进行评价.方法 成年♂SD大鼠随机分为两组:正常对照组(CON组,n=8)和

  2. 采用DNA修饰的金电极表面电化学方法对阿霉素与DNA相互作用的研究%DNA modified gold surface electrochemical method for determining the interaction of adriamycin with DNA

    Institute of Scientific and Technical Information of China (English)

    周宪梁; 张慧敏; 傅春燕; 甄一松; 邹玉宝; 刘玉清; 惠汝太

    2004-01-01

    众所周知,阿霉素是一种抗肿瘤药物,并能引起严重的心脏副作用.它的疗效和副作用被认为是由于它与DNA之间存在有相互作用.人们已采用不同的方法对DNA和阿霉素的相互作用进行了研究,但是由于实验方法本身的限制和实验条件的不同,很难得到统一的结果.为了研究阿霉素和DNA之间相互作用的机制,我们采用DNA修饰的金电极表面电化学方法对阿霉素与DNA相互作用进行了研究,结果发现,在酸性溶液中,阿霉素带正电荷,dsDNA带负电荷,两者之间的相互作用主要是静电结合.随着pH值的增加,在中性溶液中,阿霉素与dsDNA的相互作用是嵌入结合.另外,在酸性溶液中,吸附在电极表面的ssDNA与阿霉素之间存在有静电作用.这些结果为深入理解阿霉素与DNA的相互作用提供了帮助.%It has long been known that adriamycin is an antitumor antibiotics with severe cardiac side effects.Both its therapeutic and side effects is believed to result from its interaction with DNA.Various methods have been used to study the interaction,but no consistent results could be generated due to problematic methods and experimental conditions.To investigate the physical interaction of adriamycin with DNA,we used a DNA modified gold surface electrochemical electrode method and found that in acidic solution,the electrostatic interaction plays the dominant role between positively charged adriamycin and negatively charged dsDNA.With pH increasing,in neutral solution,the interaction of dsDNA with adriamycin is intercalation.Additionally,it was found that in acidic solution,the ssDNA adsorbed on gold surface can also interact with adriamycin by electrostatic action.These results will be useful for further understanding the interaction of DNA with adriamycin.

  3. Effect of p53 Inhibitor-α on Adriamycin Induced Apoptosis of Cultured Human Skin Keratinocytes in Vitro%p53抑制剂PFT-α对阿霉素诱导的人皮肤角质形成细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    张兴洪; 刘彦群; 魏志平; 田美华

    2011-01-01

    Objective To investigate the effect of p53 inhibitor-α (PFT-α) on adriamycin induced apoptosis of cultured human skin keratinocytes in vitro.Methods Human skin keratinocytes were cultured with 0, 4, 8, 12 mg/L PFT-α and adriamycin.Cell proliferation was detected by colorimetric assay of MTT.The optical density (OD) values were read on a scanning multiwell spectrophotometer (ELISA reader).Apoptosis rate of human skin keratinocytes was detected by flow cytometry.Results The proliferation of human skin keratinocytes was inhibited by adriamycin.If cells were pre-incubated with 8, 12mg/L PFT-α, OD value was significant higher and apoptosis induced by adriamycin was suppressed compared with control group (P <0.05).Conclusion This study suggested that PFT-α could partially inhibit adriamycin induced apoptosis of cultured human skin keratinocytes.%目的 探讨p53抑制剂PFT-α对阿霉素诱导的人皮肤角质形成细胞凋亡的影响.方法 用MTT法通过比色分析测定吸光度(OD)值,检测0,4,8,12mg/L PFT-α和阿霉素给药对角质形成细胞增殖的影响,用流式细胞仪检测细胞凋亡.结果 阿霉素抑制体外培养的人皮肤角质形成细胞增殖,先给予8,12mg/L PFT-α处理细胞,然后给予阿霉素,与对照组比较,PFT-α升高OD值(P<0.05),降低细胞凋亡率(P<0.05).结论 先行给予适当剂量PFT-α处理人皮肤角质形成细胞,能一定程度减轻阿霉素对人皮肤角质形成细胞的损伤,表现出对阿霉素致凋亡的保护作用.

  4. Effect of Antisense p53 Oligodeoxynucleotides on Adriamycin Inducing Apoptosis of Cultured Human Skin Keratinocytes in Vitro%反义p53寡核苷酸对阿霉素诱导的培养人皮肤角质形成细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    张兴洪; 刘彦群; 田美华

    2011-01-01

    Objective To investigate the effect of antisense p53 oligodeoxynucleotides (ODN) on adriamycin inducing apoptosis of cultured human skin keratinocytes in vitro. Methods Human skin keratinocytes were cultured with 2mg/L adriamycin and transfected with 0.5mg/L antisense p53 ODN and different concentrations of liposome. Cell proliferation was detected by colorimetric assay of MTT. Then the optical density values were measured on a scanning multiwell spectrophotometer (ELISA reader). The mRNA of p53 was also observed by RT-PCR after transfection with antisense p53 ODN. Apoptosis rate of human skin keratinocytes was detected by flow cytometry. Results We found that the proliferation of human skin keratinocytes was inhibited by adriamycin. If cells were incubated with 0.5mg/L antisense p53 ODN and 5mg/L or 10mg/L liposome, p53 mRNA decreased. A value was significantly higher and apoptosis induced by adriamycin was suppressed (P<0.05). Conclusion This study suggests that antisense p53 ODN could partially inhibit adriamycin inducing apoptosis of cultured human skin keratinocytes.%目的 探讨反义p53寡核苷酸(ODN)对阿霉素诱导的培养人皮肤角质形成细胞凋亡的影响.方法 用MTT法检测不同浓度脂质体和0.5mg/L反义p53 ODN转染角质形成细胞后对2mg/L阿霉素抑制细胞增殖的影响;RT-PCR方法 测定p53 mRNA水平的变化;用流式细胞仪检测细胞凋亡.结果 阿霉素抑制体外培养的人皮肤角质形成细胞增殖,5mg/L、10mg/L的脂质体和0.5mg/L反义p53ODN转染细胞后,p53mRNA水平下降(P<0.05),细胞增殖能力增强(P<0.05),凋亡率降低(P<0.05).结论 给予适当剂量反义p53 ODN转染人皮肤角质形成细胞,能一定程度减轻阿霉素对细胞的损伤,表现出对阿霉素致凋亡的保护作用.

  5. Long-term results of a randomized trial comparing cisplatin with cisplatin and cyclophosphamide with cisplatin, cyclophosphamide, and adriamycin in advanced ovarian cancer. GICOG (Gruppo Interregionale Cooperativo Oncologico Ginecologia), Italy.

    Science.gov (United States)

    1992-05-01

    We report the long-term results of a randomized trial comparing cisplatin (P) with cisplatin and cyclophosphamide (CP) with cisplatin, cyclophosphamide, and adriamycin (CAP) in advanced ovarian cancer. Overall, this update confirms previously published data on 529 cases. Median survival times for the three treatments--CAP, CP, and P--are, respectively, 23, 20, and 19 months. The differences among the three arms are still nonsignificant and the estimated percentage survival at 7 years and confidence limits are, respectively, 21.7 (14.9-28.4), 17.0 (11.0-22.9), and 12.2 (6.9-17.4). According to the results of the Cox regression model on prognostic factors, higher grading, a larger residual tumor size, and performance status less than 80 (Karnovsky) all were independently associated with a poorer outcome, while a serous histotype was related to a better prognosis. The other variables (age, stage, center, type of surgery) initially included in the model did not appear to be significantly related to prognosis. The implications of these long-terms results relative to the application of combination chemotherapy with CAP or CP are discussed.

  6. Research on the Protective Effect of Oxymatrine in Cardiac Injury of Rats Induced by Adriamycin%氧化苦参碱对阿霉素所致大鼠心肌损伤的保护作用研究

    Institute of Scientific and Technical Information of China (English)

    刘洋; 杨益鹏; 姚忠彬; 张扬; 范蕾; 卢均坤

    2013-01-01

    目的:研究氧化苦参碱对阿霉素致大鼠心肌损伤的保护作用.方法:SD大鼠随机分成4组,阿霉素组(adriamycin,ADM)、阿霉素+氧化苦参碱组(oxymatrine,OMT),氧化苦参碱组,正常对照组.免疫组化染色法检测大鼠心肌Ⅰ,Ⅲ型胶原的表达,用光镜及电镜观察心肌组织的病理改变及超微结构变化.结果:ADM组中大鼠心肌Ⅰ,Ⅲ型胶原的表达显著增加,ADM+OMT组也有相似改变,但较ADM组有显著下降,两组之间有显著差异(P<0.05);正常对照组与OMT组无变化.光镜及电镜结果显示ADM组与ADM+OMT组大鼠心肌组织,均有损伤,但ADM+OMT组较ADM组损伤明显减轻.OMT组动物未观察到心肌组织病理变化.结论:氧化苦参碱对阿霉素所致大鼠心肌损伤具有保护作用.

  7. Protective effects of oxymatrine on adriamycin-induced cardiotoxicity in rabbits and its mechanism%氧化苦参碱对兔阿霉素心肌损伤保护作用及其机制研究

    Institute of Scientific and Technical Information of China (English)

    马飞; 李小平; 顾建春; 章莉; 郑磊贞

    2009-01-01

    Objective To establish the in vivo models of adriamycin(ADR)-induced cardiotoxicity in rabbits, investigate the protective effect of oxymatrine (OMT) on ADR-induced cardiotoxicity, and explore the possible mechanism. Methods Twenty-six rabbits were randomly divided into ADR group (n=8, 2 mg/kg ADR), OMT group (n=5, 10 mg/kg OMT), ADR + OMT group (n=8, 10 mg/kg OMT was injected 30 min before ADR injection) and saline group (n=5, same quantity of normal saline), and rabbits in each group were infused with medicine or normal saline through ear marginal vein once a week for 8 weeks. The apoptosis of myocardial cells was detected by TUNEL methods, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) was determined. Results After treatment, the body weight of ADR group was significantly lower than that of the other groups(P < 0.05), the activity of SOD and GSH-Px significantly decreased and the apoptosis index (AI) was significantly higher than that of the other groups(P <0.01). There were similar while minor changes in ADR + OMT group. There was no significant adverse effects in OMT group. Conclusion OMT protects heart from adriamycin-induced injury in rabbits, which may relate to the decrease in level of antioxidant and apoptosis of myocardial cells.%目的 通过建立兔在体阿霉素(ADR)心肌损伤模型,研究氧化苦参碱(OMT)注射液对兔ADR损伤心肌功能的保护作用.并探索其可能机制.方法 26只新西兰大白兔随机分为4组,均经耳缘静脉缓慢注药,每周1次,共8周.①ADR组(n=8):注射2 mg/kg ADR;②OMT组(n=5):10 mg/kg OMT.③ADR+OMT组(n=8):每次注射ADR前30 min,先注射10 mg/kgOMT;④生理盐水(NS)组:以相同方法注射等量生理盐水.TUNEL法原位定性检测心肌细胞凋亡情况.心肌组织匀浆测定超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性.结果 ADR组用药后体质量明显低于其他组(P<0.05),SOD和GSH-Px活性明显降低(P<0.05),凋

  8. 黄蜀葵花对阿霉素肾病大鼠足细胞的保护作用%Protective effect of Sunset Abelmoschus on podocyte injury in adriamycin-induced nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    边琪; 郭志勇; 胡海燕; 李娟

    2012-01-01

    目的 探讨黄蜀葵花(黄葵)治疗阿霉素肾病大鼠的疗效及其对足细胞病变的影响.方法 雄性SD大鼠50只,按随机数字法分为假手术组(n=10)、模型组(n=10)、黄葵低剂量组(0.5 g·kg-1·d-1,n=10)、黄葵中剂量组(1.0 g·kg-1·d-1,n=10)和黄葵高剂量组(2.0 g·kg-1·d-1,n=10).采用单侧肾切除联合两次阿霉素(ADR)注射法,制备阿霉素肾病大鼠模型.黄葵各组于右肾摘除术当天起给予相应剂量黄葵溶液灌胃.分别在术前、术后2、4、6、8周末检测大鼠尿蛋白、尿N-乙酰葡萄糖氨基转移酶(NAG)、血清白蛋白、Scr和血脂.第8周末宰杀大鼠,取肾组织行光镜和电镜检查,并观察肾组织nephrin的分布.结果 与模型组比较,黄葵各组在各时间点的尿蛋白量和尿NAG水平均降低,以高剂量组最显著(P<0.01);且血浆白蛋白增加,血脂紊乱改善,差异均有统计学意义(P<0.05).模型组及黄葵各治疗组Scr自第4周起较假手术组明显升高;第8周末,黄葵高剂量组Scr低于模型组(P<0.05).黄葵各组肾小球球性硬化和节段硬化比例均低于模型组,肾小管间质损害改善,且以高剂量组最显著.与模型组比较,黄葵各组足细胞的足突损伤减轻,足突融合程度和范围均有所改善,以高剂量组最显著.黄葵各组肾组织nephrin表达较模型组增加.结论 黄葵能减少阿霉素肾病大鼠的蛋白尿,减轻肾组织损伤和慢性化,其机制可能与改善足细胞病变有关.%Objective To explore the effect of Sunset Abelmoschus on podocyte injury in adriamycin-induced nephropathy rats.Methods Fifty male SD rats were randomly divided into five groups:sham operation group (n=10),model group (n=10),Sunset Abelmoschus low dose group (0.5 g·kg-1· d-1 n=10),middle dose group (1.0 g· kg-1· d-1,n=10) and high dose group (2.0 g· kg-1· d-1,n=10).Unilateral nephrectomy combined repeated adriamycin injection were performed to establish

  9. Effect of fibrocytes on the progressive renal fibrosis induced by adriamycin%纤维细胞在大鼠多柔比星慢性肾损害模型肾纤维化过程中的作用

    Institute of Scientific and Technical Information of China (English)

    王显; 张伯科; 沈雯雯; 周琪

    2010-01-01

    Objective To investigate the effect of fibrocytes and chemokine recepter 7(CCR7)on the process of renal fibrosis induced by adriamycin in rats.Methods Male Sprague-Dawhy(SD)8 weeks old rats(n=52)were divided into two groups randomly,normal control group(CG,n= 20)and model group(MG,n=32).MG rats were injected with 4 mg/kg of adriamycin via tail vein on the first day of the 1st and 2nd week,respectively,while CG rats received 0.9% sodium chloride solution injection of equal volume at the same time.The urine and serum samples were measured at the end of 4,7,10 and 13 weeks after the first administration of adriamycin to observe biochemical changes,while the renal tissue of rats was obtained to evaluate renal histological and uhrastructural changes by glomerulosclerosis index and tubulointerstitial index,and to analyze the expression of CD45,collagen Ⅰ and CCR7 by immunohistochemistry.Results Compared with CG,levels of 24 h urine protein excretion rate(mg,568±102 vs 21±6,P<0.01),serum cholesterol(CHO,mmol/L,6.79±1.47 vs 1.29±0.27,P<0.01)and triglyceride(TG,mmol/L,2.57±1.19 vs 0.76±0.11,P<0.01)increased significantly,whereas serum albumin(Alb,g/L,21.41±2.11 vs 34.64±0.96,P <0.01)decreased significantly in the 7th week in MG.The proliferation of mesangial cells,the accumulation of the extracellular matrix and atrophyin or extension of renal tubules in MG were more remarkable than those in CG.There were some cells which expressed CD45 and collagen Ⅰ simultaneously in the serial sections of renal tissue and renal cortical interstitium in MG.Interstitial infiltration of CD45+or CCR7+cells appeared in the 4th week,reached a maximum in the 7th week(P<0.01)and gradually decreased afterward.Conclusions Fibrocytes may be involved in the earlier stage of kidney fibrosis.The immigration of this population from peripheral blood to renal lesion site is possible to be associated with CCR7protein.%目的 以多柔比星慢性肾损害大鼠为对象,探讨纤维

  10. Experimental study of high frequency echocardiography in evaluation of left ventricular function produced by adriamycin in rats%高频超声评价阿霉素造模大鼠心功能的实验研究

    Institute of Scientific and Technical Information of China (English)

    张书杰; 姜凡; 解翔; 张野; 吴运香; 张新书

    2012-01-01

    目的 评价高频超声心动图在阿霉素(ADM)造模大鼠心力衰竭研究中的价值.方法 30只SD大鼠随机分成对照组、ADM组.大鼠尾静脉注射ADM制成心力衰竭模型.对两组大鼠行经胸高频超声心动图监测.分别取两组大鼠的心肌组织行HE染色及VG染色.结果 高频超声心动图可以清晰显示大鼠的心脏结构,经超声测定ADM组与对照组心功能变化比较差异有统计学意义(P<0.01).经高频超声心动图所证实的心力衰竭大鼠,HE染色及VG染色结果均证实其心肌组织明显受损.结论 经胸高频超声心动图可以无创、准确地评价ADM造模大鼠心功能的改变,与病理结果一致.%To assess the effect of high frequency echocardiography on cardiac failure of rats produced by adriamycin ( ADM, doxorubicin ). Methods 30 SD rats were randomly divided into control group and ADM group. The model of cardiac failure of rats was made by injecting ADM into their tail veins. Then we observed two groups of rats with high frequency echocardiography. The myocardiac tissue of rats was observed by HE staining and VG staining method. Results High frequency echocardiography could reveal vividly the structure of rats' hearts. There was statistical significance between the normal control group and the ADM group in the changes of heart function which was concluded by high frequency echocardiography ( P < 0. 01 ). The results of HE staining and VG staining of rats' myocardiac tissue also proved that there was obviously injury. Conclusion High frequency echocardiography is an accurate and noinvasive method in assessing the changes of heart function of rats, and it is in according with phathology.

  11. 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

  12. Prednisone inhibits the focal adhesion kinase/receptor activator of NF-κB ligand/mitogen-activated protein kinase signaling pathway in rats with adriamycin-induced nephropathy.

    Science.gov (United States)

    Ye, Minyuan; Zheng, Jing; Chen, Xiaoying; Chen, Xuelan; Wu, Xinhong; Lin, Xiuqin; Liu, Yafang

    2015-11-01

    The aim of the present study was to investigate the mechanisms underlying the effects of prednisone on adriamycin-induced nephritic rat kidney damage via the focal adhesion kinase (FAK)/receptor activator of nuclear factor-κB ligand (RANKL)/mitogen‑activated protein kinase (MAPK) signaling pathway. An adriamycin‑induced nephritic rat model was established to investigate these mechanisms. A total of 30 healthy male Sprague‑Dawley rats were randomly assigned to the normal, model or prednisone group. Samples of urine were collected over the course of 24 h at days 7, 14, and 28, and renal cortex tissue samples were harvested at days 14, and 28 following nephritic rat model establishment. The total urinary protein content was measured by biuret colorimetry. Pathological changes in the kidney tissue samples were observed using an electron microscope. The mRNA expressions levels of FAK, RANKL, p38, extracellular signal‑regulated kinase (ERK), c‑Jun N‑terminal kinase (JNK), and nephrin were then quantified by reverse transcription‑quantitative polymerase chain reaction. In addition, the protein expressions levels of FAK, RANKL, p38, ERK, JNK, phosphorylated (p)‑FAK, p‑ERK, and p‑JNK were quantified by western blotting. As compared with the normal group, the protein expression levels of FAK, RANKL, p-FAK, p38 and p-ERK in the model group were increased. In the prednisone group, the protein expression levels of p-ERK decreased, as compared with the normal group. In the prednisone group, the urinary protein levels, the protein expression levels of FAK, RANKL, p38, p-FAK, p-p38 and the mRNA expression levels of FAK, p38, RANKL, ERK, JNK decreased, as compared with the model group. In the prednisone group, the mRNA and protein expression levels of nephrin and the serum expression levels of RANKL increased, the serum expression levels of osteoprotegerin (OPG) were decreased, as compared with the model group. No significant changes in the protein expression

  13. Effects of different administrative routes on target distribution of magnetic albumin nanoparticles containing adriamycin in vivo%不同给药途径对磁性白蛋白纳米粒靶向分布的影响

    Institute of Scientific and Technical Information of China (English)

    张阳德; 龚连生; 潘一峰; 李异凡; 黄秋林; 彭健; 刘勤

    2003-01-01

    Objective:To determine a significantly effective administration route for hepatocarcinoma therapy using magnetic albumin nanoparticles carrying Adriamycin. Methods: Magnetic albumin nanoparticles labeled with 125I were injected into rats bearing hepatocarcinoma via different administrative ways (via hepatic artery, portal vein and jugular vein). Distribution of magnetic albumin nanoparticles was determined through 125I count and histological analysis. Results: Under magnetic field, albumin nanoparticles deposited in the target area (hepatocarcinoma tissue)at large degree, and the density of albumin nanoparticles in non- target area decreased significantly. Meanwhile,magnetic nanoparticle concentration was the highest at targeted tumor (P < 0.01 ) and the lowest at non- targeted normal liver tissue and lungs (P <0.01 ), and embolism effect in the target area was the best via hepaticartery administration in comparison with the other two administrations. Conclusions: The administration of albumin nanoparticles via hepatic artery under guidance of an external magnetic field was the most effective way for hepatocarcinoma therapy of rat.%目的该实验旨在比较外置定位磁场与否,各组的肝癌区(磁靶区)、正常肝和肺组织的克组织放射量以及肝癌区血管栓塞程度,以探求一种较佳的给药途径和方法.方法用125I标记磁性白蛋白纳米粒,经药肝癌鼠的肝动脉、门静脉及颈静脉三种不同途径给药.结果外置磁场使磁性白蛋白纳米粒在靶区定位聚集,减少其在非靶区的分布;外置磁场下经肝动脉给药组的肝癌组织区克组织放射量最高(P<0.01),而正常肝和肺组织的克组织放射量最低(P<0.01),肝癌区血管栓塞程度也明显高于经门静脉及经颈静脉组.结论外置定位磁场下,经动脉途径注入磁性白蛋白纳米粒的磁靶向化疗栓塞效果最好.

  14. Therapeutic effects of Thesium chinensis on adriamycin-induced nephropathy rats%百蕊草对阿霉素肾病大鼠治疗作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    宣伟东; 唐大海; 卞俊; 胡水根; 胡建峰; 范正平

    2012-01-01

    Objective To investigate the therapeutic effects of Thesium chinensis Turcz on Adriamycin-induced nephropathy rats. Methods 40 SD rats were divided into 4 groups averagely: normal control group, model control group, low-dosage group (1.0 g/( kg · d) and high-dosage group(5. 0 g/( kg · d). Nephritic syndrome models were established in 30 rats by intravenous injection of Adriamycin (6.0 mg/kg ). The rats of low-dosage group and high-dosage group were intragastric administrated decoction of Thesium chinensis Turcz daily, the model control group rats were given running water(2 ml). During 5 weeks treatment process, the 24 hour u-rine volume, 24 hour urine protein concentration of rats were observed. The level of total serum protein(TP) , serum albumin( ALP) , total cholesterol( TCH) , triglyoerides( TG) and UREA were determined, and the pathological changes of kidney tissue were assayed after the therapy process. Results The symptoms of nephritic syndromes, such as edema, tail-rot disease, were relieved by Thesium chinensis Turcz. After 2 weeks therapy, the 24 hour urine volume of low-dosage group and high-dosage group were significantly higher than model control, and the 24 hour urine protein concentration were significantly lower than model control after 3 weeks. The level of TP and ALP of low-dosage group were significantly higher than model control, as well as the level of TCH and TG were significantly lower after 5 weeks. Conclusion Thesium chinensis Turcz could eliminate tissue edema and decrease the urine protein concentration by diuretic action and improves renal pathology to protect the kidney from damage by reducing the serum cholesterol level, decreased blood lipid content, and increased the plasma protein level.%目的 观察百蕊草对大鼠肾病综合征的治疗作用.方法 SD大鼠40只,10只为空白对照组,余下分为模型组,低剂量组(1.0 g/(kg·d)),高剂量组(5.0 g/(kg·d)),每组10只,尾静脉注射阿霉素6.0 mg/kg建立

  15. 2-DG enhances chemosensitivity of breast cancer cells to adriamycin%2-DG增强乳腺癌细胞对阿霉素化疗敏感性的作用

    Institute of Scientific and Technical Information of China (English)

    程秀; 刘浩; 方琳; 苏方; 宋乐乐; 马琳艳; 蒋国君; 张旭东; 蒋志文

    2010-01-01

    目的 探讨糖基化抑制剂(2-deoxy-D-glucose,2-DG)对阿霉素(adriamycin, ADM)抗肿瘤作用的影响,以期为乳腺癌的治疗提供新的靶点.方法 MTT法检测不同浓度(0、1.25、2.5、5、10、20 mmol·L-1 )2-DG、不同浓度(0、0.625、1.25、2.5、5、10 mg·L-1)ADM以及ADM与2-DG(10 mmol·L-1)合用对乳腺癌细胞Sk-Br-3的增殖抑制作用.溴化丙啶(propidium iodide, PI)单染检测2-DG(10 mmol·L-1)对ADM诱导乳腺癌细胞Sk-Br-3凋亡的影响;Western blot检测2-DG (10 mmol·L-1 )处理Sk-Br-3细胞不同时间(0、9、24、36 h)葡萄糖调节蛋白78 (glucose-regulated protein 78,GRP-78)、Caspase-3的表达以及联合ADM处理不同时间(0、9、24、36 h)GRP-78的表达;2-DG(10 mmol·L-1)对ADM(0.4 mg·L-1)诱导乳腺癌细胞Sk-Br-3所致Caspase-3活性的变化;实验中检测了2-DG及ADM合用对集落克隆形成的影响.结果 10 mmol·L-1 2-DG对乳腺癌细胞Sk-Br-3的24、48、72 h增殖抑制率分别为80.73%、75.16%、70.13%,而诱导Sk-Br-3细胞凋亡率仅为5.8%.10 mmol·L-12DG与ADM联合刺激乳腺癌细胞Sk-Br-3 48 h的凋亡率为58.11%,高于ADM本身诱导凋亡率35.12%,且2-DG可增强ADM抑制乳腺癌细胞Sk-Br-3的集落克隆形成的作用.2-DG能上调GRP-78以及Caspase-3的活性.结论 2-DG能增加ADM诱导乳腺癌细胞的凋亡,其机制可能通过引起过度的内质网应激反应以及增加Caspase-3的活性.

  16. 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

  17. CAV1基因沉默增强MCF-7多细胞球对多柔比星的敏感性%CAV1 gene silencing enhances adriamycin sensitivity of breast carcinoma MCF-7 multicellular spheroids

    Institute of Scientific and Technical Information of China (English)

    顾栋桦; 平金良; 董吉顺; 朱荣; 陈琦

    2011-01-01

    carcinoma to adriamycin (ADM) through the use of the RNA interfering technique. Methods: MCF-7 MCS were obtained from liquid overlay technique culture, and CAV1 -targeted small interfering double-stranded RNAs (siRNA) were introduced into MCF-7 cells by Lipofectamine?2000. ADM resistance was detected with trypan blue exclusion testing. CAV1 mRNA and protein levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The relative phosphorylation level of focal adhesion kinase (FAK) was assessed by Western blot. Results: Compared with monolayer cells, MCS showed lower cell inhibitory rate after ADM exposure for 24 h, and the relative phosphorylation level of FAK was elevated in MCS by 2.64-fold. CAVl-targeted RNA interference markedly inhibited the expression of CAV1 gene and suppressed formation of MCF-7 MCS. Cell inhibitory rate of ADM was enhanced by 1.07-fold and the relative phosphorylation level of FAK was reduced by 68.7% by CAV1 gene silencing in MCF-7 MCS. Conclusion: MCS cultures induce MCF-7 resistance to ADM. RNA interference to target CAV1 gene can restore sensitivity to ADMin MCS, and down-regulation of FAK phosphorylation may be involved in its mechanism.

  18. Effect of Interleukin-18 Binding Protein on Adriamycin Nephropathy Model Mice%白细胞介素18结合蛋白对多柔比星肾病模型小鼠的疗效

    Institute of Scientific and Technical Information of China (English)

    董孟华; 杨东霞

    2011-01-01

    Objective To explore the experimental therapeutic effect of interleukin - 18 binding protein ( IL - 18BP) through binding endogenous IL - 18 inhibit downstream inflammation factors releasing on adriamycin(ADR) - induced nephropathy in mice.Methods Kunming mice were induced to nephropathy model by single injection of ADR(7.5 mg · kg- 1 ) through tail vena.Then the mice were treated with murine- IL- 18BP with 0.5 mg · kg-1 as the IL- 18BP- treated group,and the mice were treated with phosphate buffered saline(PBS) of the same volume as the ADR -minimal change nephropathy(MCN) group on day 5,7,12 and 21.Urine protein was measured biweekly and objective sign of mice were recorded.All mice were sacrificed through getting blood from the heart on the 42th day after the first injection of ADR.The renal histological changes were observed under electron microscope when mice were sacrificed.Results 1.All ADR - mice developed nephropathy characterized by proteinuria, hypoalbuminemia, hypereholasterolnemia, and progressive renal injury.2.In IL - 18 BP - treated group,the urine protein rates decreased significantly compared with those in ADR -MCN group,but increased significantly compared with those in normal control group( Pa <0.01 ).3.In ADR - MCN group,the levels of tiglyceride and cholesterol were higher,and total protein and albumin were lower than those in IL- 18BP -treated group and normal control group in serum( Pa < 0.01 ).There were no significant difference among three groups of the levels of blood urea nitrogen and serum creatinine( Pa > 0.05 ).4.In IL- 18 BP -treated group, the levels of IL- 18 ,interferon- γ( IFN- γ) and tumor necrosis factor-α (TNF-α ) in serum decreased significantly compared with those in ADR-MCN group ( Pa < 0.05 ), the level of IL - 4 rose again ( P < 0.01 ).5.In ADR - MCN group, glomerulus epithelical cells were hologamy or vanished,yet there were only meromixis in IL - 18BP - treated group by transmission electron microscope

  19. 蛇毒组分对K562阿霉素敏感株和耐药株的抑制作用%Snake venom components inhibits growth of K562 adriamycin-sensitive and-resistant strains

    Institute of Scientific and Technical Information of China (English)

    杨昌山; 何慧华; 董伟华

    2013-01-01

    目的:通过对中华眼镜蛇毒进行分离和各组分的初筛,寻找逆转K562对阿霉素耐药的活性成分KD-Ⅲ-1,为今后研究肿瘤耐药性奠定工作基础。方法:通过凝胶分离得到的蛇毒组分分别作用于K562对阿霉素耐药株K562/A和敏感株K562/S,筛选有效活性组分;通过荧光探针Rh123测定P-gp蛋白活性和PI染色进一步确定该组分的逆转K562/A的耐药活性。结果:分别给予2μg/mL阿霉素( Adr)和各浓度蛇毒组分处理24 h后,可以发现蛇毒组分对阿霉素敏感株K562/S和耐药株K562/A都有明显的抑制作用,并呈现出剂量-效应关系。1μg/mL蛇毒组分处理组与2μg/mL蛇毒处理组抑制作用明显;在药物持续作用48 h后对K562/A的活性仍有抑制作用在0.5、1、2μg/mL的蛇毒组分组表现的更加明显。通过Rho外排实验发现蛇毒粗毒组平均荧光强度(MFI)与阴性对照组没有明显差异,而2.5μg/mL蛇毒组分组的MFI明显降低,与对照组相比具有统计学意义(P<0.05)。2.5μg/mL蛇毒粗毒和分离组分分别对K562/S敏感株和K562/A耐药株作用3 h后,K562/S的PI染色阳性率明显升高,而K562/A的PI染色阳性率并没有明显升高。结论:蛇毒组分KD-Ⅲ-1对K562/A和K562/S细胞均有明显抑制的作用,抑制作用可能与诱导凋亡有关。%Objective:To explore the active ingredient, KD-Ⅲ-1, for reversal of K562 resistance to adriamycin ( Adr) via separation and primary screening of individual components of cobra venom, thus offering the sound basis for future study on tumor drug resistance. Methods: The K562 Adr-resistant strains, K562/A, and -sensitive strains, K562/S, were incubated with isolated snake venom components derived from gel separation, for exploration of the effective component. The P-gp protein activity was measured by the fluorescent probe Rh123, and the PI staining was applied to determine the resistance reversal capacity of the components

  20. 脂质体阿霉素和热疗对脑胶质瘤细胞的影响%Effects of liposome-adriamycin (L-ADM) and thermotherapy on glioma cells: an experimental study

    Institute of Scientific and Technical Information of China (English)

    史正华; 张剑宁

    2013-01-01

    Objective To observe the effects of liposome-adriamycin (L-ADM) and thermotherapy on proliferation and apoptosis of SWO-38 glioma cells. Methods The SWO-38 glioma cells were cultivated in vitro. The effects of thermotherapy (43℃), ADM chemotherapy, L-ADM chemotherapy, thermotherapy + ADM chemotherapy, and thermotherapy + L-ADM chemotherapy on the cell proliferation and apoptosis were observed. The working concentration of ADM and L-ADM, and the cell proliferation rate were determined by MTT method. The apoptotic rate was determined by flow cytometry. Results The proliferation inhibition rate of thermotherapy + L-ADM chemotherapy and thermotherapy + ADM chemotherapy was 80.16% ± 3.78% and 62.09% ± 3.05%, respectively, and it was significantly higher than that of L-ADM chemotherapy (40.27% ± 2.32%), ADM chemotherapy (30.56% ± 2.03%) or thermotherapy (16.51% ± 1.26%, P<0.05), and the proliferation inhibition rate of thermotherapy + L-ADM chemotherapy was higher than that of thermotherapy + ADM chemotherapy (P<0.05). The apoptotic rate of thermotherapy + L-ADM chemotherapy and thermotherapy + ADM chemotherapy was 84.19% ± 2.69% and 60.29% ± 1.47%, respectively, and it was significantly higher than that of L-ADM chemotherapy (46.72% ± 2.09%), ADM chemotherapy (35.09% ± 1.46%) and thermotherapy (17.85% ± 0.78%, P<0.05), and the apoptotic rate of thermotherapy + L-ADM chemotherapy was higher than that of thermotherapy + ADM chemotherapy (P<0.05). Conclusion Thermotherapy can enhance proliferation inhibition and apoptosis induction effect of ADM and L-ADM on SWO-38 glioma cells, and this effect is even stronger with L-ADM.%目的 探讨脂质体阿霉素和热疗对脑胶质瘤细胞的增殖抑制及凋亡诱导作用.方法 体外培养人脑胶质瘤细胞SWO-38,采用水浴加温法,观察单纯热疗、阿霉素化疗、脂质体阿霉素化疗、热疗+阿霉素化疗、热疗+脂质体阿霉素化疗对细胞增殖及凋亡的影响.MTT法确

  1. RNA干扰MDR1基因对乳腺癌多细胞球阿霉素敏感性的影响%Effect of MDR1 Gene Silencing on Adriamycin Sensitivity of Breast Carcinoma Multicellular Spheroids by RNA Interference

    Institute of Scientific and Technical Information of China (English)

    郑庆玲; 顾栋桦; 平金良; 朱荣; 陈琦

    2011-01-01

    目的 通过RNA干扰沉默MDR1基因,探讨后者在乳腺癌多细胞球阿霉素耐药中的作用.方法 用liquid overlay技术培养获得多细胞球(multicellular spheroids, MCS),用脂质体转染法把特异针对MDR1基因的双链小RNA干扰片段导入MCF-7细胞中,采用台盼蓝拒染法检测阿霉素对MCF-7的细胞抑制率,MDR1 mRNA水平及蛋白水平分别用RT-PCR和免疫印迹法检测,用荧光光度计法检测阿霉素在细胞内的蓄积情况.结果 多细胞球形成后,阿霉素对MCF-7细胞的抑制率明显减少,MDR1 mRNA及蛋白水平明显升高,阿霉素在细胞内的蓄积量减少;RNA干扰法能明显抑制MDR1基因表达,增加阿霉素在MCS细胞中的蓄积,提高阿霉素对MCS的细胞抑制率.结论 多细胞球的形成可以增强MCF-7细胞的阿霉素耐药性,RNA干扰沉默MDR1基因可以部分逆转MCF-7多细胞球的阿霉素耐药.%Objective To investigate the role of MDRI gene expression in drug resistance of multicellular spheroids of breast carcinoma to Adriamycin( ADM) by RNA interfering technique. Methods MCF - 7 multicellular spheroids were obtained from liquid overlay technique culture. MDR1 - targeted small interfering double - stranded RNAs ( SiRNA) were introduced into MCF - 7 cells by lipofectamine. Adriamycin resistance was detected with trypan blue exclusion testing. MDR1 mRNA and MRD1 protein levels were determined by reverse transcroption - polymerase chain reaction( RT - PCR) and Westernblot, and Adriamycin accumulation in MCF - 7 cells was tested by fluorescence spectrophotometry. Results Compared with monolayer cells, MCS showed lower cell inhibitory rate and ADM accumulation in cells after ADM expoaure for 24h, and both mRNA and protein level of MDRI were elevated in MCS obviously. RNA inter ference markedly inhibited the expressiong of MDRI mRNA and protein, and enhanced the intracellular accumulation of andpartially restored sensitivity to ADM in MCF -7 MCS. Conclusion Breast

  2. 普罗布考对肾小球硬化大鼠肾组织转化生长因子β1的影响%Effect of Probucol on the Expression of Transforning Growth Factor-β1 in the Kidney of Rats with Adriamycin Induced Glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    苏雪松; 周光宇; 杜丰; 李德天

    2011-01-01

    观察普罗布考对阿霉素致肾小球硬化大鼠肾组织转化生长因子β1(TGF-β1)的影响.方法 建立单侧肾切除加重复注射阿霉素诱导的肾小球硬化大鼠模型,分为模型组和治疗组,设假手术组为对照组.检测各组大鼠第0、4、8、12周尿蛋白排泄量,并于12周末测定各组大鼠血清肌酐、尿素氮及血清白蛋白;行肾脏病理学检查计算肾小球硬化指数;应用免疫组化方法检测肾组织中TGF-β1的表达.结果 与模型组相比,普罗布考治疗组大鼠24h尿蛋白定量明显减少,血清肌酐、尿素氮及血清白蛋白等指标均有不同程度的改善(P<0.05),肾小球硬化程度减轻(P<0.05),肾小球内TGF-β1沉积明显减少(P<0.05).结论 普罗布考对阿霉素致肾小球硬化大鼠肾脏有部分保护作用,其机制可能与抑制TGF-β1的表达有关.%Objective To study the effect of probucol on (he expression of transfoiming growth factor-B, (TGF-B,) in the kidney of rats with adriamycin induced glomerulosclerosis. Methods Unilateral-nephrectomized and adriamycin-induced glomerulosclerosis rat models were established and randomly divided into model group and probucol-treated group,while rats underwent sham-operation were served as the normal control group. At 0,4,8,12 weeks,the 24-hour urinary protein of the rats from each group were measured. After 12 weeks,serum crea-unine (SCr),blood urea nitrogen (BUN) and serum albumin (ALB) were measured. The renal tissue was observed by light microscopy to calculate glomerulo-sclerosis index (GSI). The TGF-j}, expression in renal tissue were detected by immunohistochemistry. Results Compared with the glomerulosclerosis model group,24 h excretion of urinary protein was obviously decreased,and indicators such as SCr,BUN, ALB and GSI were also improved in the probucol- treated group (P< 0.05). Besides,the expression level of TGF-B! In renal tissue was significantly lower than that in the model group (P < 0

  3. 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

  4. Inhibition of glucose regulated protein 78 in sensitizing adriamycin-induced apoptosis of human breast cancer cells%抑制葡萄糖调节蛋白78表达对阿霉素诱导人乳腺癌SK-BR-3细胞凋亡的增敏作用

    Institute of Scientific and Technical Information of China (English)

    刘宏莉; 龚萍; 刘浩; 张旭东; 蒋志文

    2010-01-01

    目的:探讨特异性下调葡萄糖调节蛋白78(GRP78)对阿霉素(adriamycin,ADR)诱导人乳腺癌SK-BR-3细胞凋亡的影响,以期为乳腺癌化疗提供新的靶点.方法:培养人乳腺癌SK-BR-3细胞,用ADR(1 mg/L)处理人乳腺癌SK-BR-3细胞0、6、12、24、36 h,Western blot检测GRP78的表达;ADR处理SK-BR-3细胞48 h后,用溴化丙啶染色测定细胞凋亡率;用小分子干扰RNA siRNA预处理SK-BR-3细胞,再予ADR同上处理,检测细胞凋亡率,比较siRNA作用前后细胞凋亡率的变化.结果:ADR可诱导内质网应激,上调GRP78的表达,SK-BR-3细胞对ADR诱导的细胞凋亡率<30%;siRNA可明显阻断GRP78的表达,显著增加ADR诱导的细胞凋亡作用,凋亡率达到(62.30±0.88)%(P<0.01).结论:抑制GRP78的表达可增强人乳腺癌SK-BR-3细胞对ADR经内质网应激途径诱导细胞凋亡的敏感性,促进肿瘤细胞的凋亡,增强其抗肿瘤作用.

  5. Evaluation of left ventricular function in rat adriamycin-induced dilated cardiomyopathy model by using echocardiography%超声心动图对阿霉素心肌病模型大鼠左心收缩功能的评价

    Institute of Scientific and Technical Information of China (English)

    郭文清; 赵子牛; 袁建军; 刘洪智

    2013-01-01

    Objective To evaluate the left ventricular (LV) function in the rat adriamycin-induced dilated cardiomyopathy model (ADR-DCM).Methods Thirty-five adult male Wistar rats were randomly divided into 2 groups.The ADR-DCM group (n =25) was injected with adriamycin at a dose of 2.5 mg/kg intravenously once a week for 10 weeks,and the control group (n =10) received an equivalent volume of 0.9% saline alone intravenously.Echocardiographic measurements were obtained at 12th week after treatment.The pathological changes of LV were examined by hematoxylin-eosin staining.Results The cumulative mortality in ADR-DCM group was 40%.As compared with control group,LV end-diastolic diameter [LVEDD,(0.67 ±0.07) cm],LV end systolic diameter [LVESD,(0.44 ±0.06) cm],and the hydroxyproline and collagen contents were significantly increased (all P < 0.01),short-axis fractional shortening (FS,33.94 ± 3.56)% and the systolic blood flow velocity of aorta (0.71 ± 0.10) m/s were significantly reduced (all P < 0.01) in ADR-DCM group.The pathological changes in ADR-DCM group were consistent with those of cardiomypathy.Conclusion (1) Chronic administration of adriamycin at a regular dose intravenously to rats could result in left ventricular myocardial fibrosis and heart falure;(2) Echocardiography can sensitively,rapidly and non-invasively evaluate the left ventricular function of the rat ADR-DCM.%目的 探讨超声心动图技术在评估阿霉素心肌病模型大鼠心功能的优势及应用价值.方法 将35只雄性Wistar大鼠按体质量随机分2组:一组制备阿霉素心肌病模型.正常对照组注射等量生理盐水.于实验第12周应用VIVID7彩色超声显像仪行二维、多普勒及M型超声检测评价其左心收缩功能,并作苏木素-伊红(HE)染色观察心肌组织学变化.结果 (1)死亡率:阿霉素心肌病组大鼠12周累计死亡10只,死亡率为40%.死亡原因为充血性心力衰竭;正常对照组无死亡.(2)大鼠心脏超声

  6. 四逆汤含药血清对心肌毒性大鼠乳鼠血清Bcl-2 Bax水平影响的研究%To Study of Effection of Blood Serum of Decoction for Treating Yang Exhaustion on Serum Baxand Bcl-2in Adriamycin Induced Cardio-toxicity in Myocardial Cell of Rat

    Institute of Scientific and Technical Information of China (English)

    王睿; 费洪新; 石小芳; 刘文华; 黄小义; 杨德助; 张腾腾

    2009-01-01

    目的:探讨四逆汤含药血清抗心肌毒性的疗效及其作用机制.方法:采用盐酸阿霉素(ADB)损伤Wistar大鼠乳鼠心肌导致心肌毒性为模型.随机分为正常组、心脏毒性ADR模型对照组、卡托普利组、四逆汤含药血清组.测定大鼠乳鼠血清Bcl-2、Bax水平,并应用光镜观察心肌组织的病理变化.结果:与正常组比较,阿霉素致心肌毒性大鼠乳鼠血清Bax水平显著降低.血清Bcl-2水平明显升高,四逆汤及卡托普利均能降低Bcl-2水平,升高Bax水平(P<0.05).光镜显示,四逆汤含药血清治疗组心肌细胞损伤程度明显低于模型组.结论:四逆汤含药血清能调节改善心肌毒性大鼠乳鼠的神经内分泌功能,拮抗过度激活的神经内分泌系统.%Objective:To explore the clinical effect and machenism of blood serum of decoction for treating yang ex-haustion on adriamycin induced cardio-toxicity in myocardial cell. Methods: Wistar rats were used to make cardio-toxicity in myocardial cell of rat model by injection of adriamyc into the peritoneum. The other 10 Wistar mrs were divided into the normal group. Model rats were randomly divided into model control group. Captopril group and blood serum of decoction for treating yang exhaustion group. Results : Compared with the normal group, serum baxlevel significantly decreased and Bcl -2level significantly increased. Compared with the model failure group, serum Bcl -2level significantly decreased and the level of baxsignificantly increased in the blood serum of decoction for treating yang exhaustion group and the Captopfil group(P < 0. 05). The degree of mycardial damage in the blood serum of decoction for treating yang exhaustion group was obviously lower than that in the model group. Conclusion: Blood senun of decoction for treating yang exhaustion can modify the nerval endocrine function of cardio - toxicity in myocardial cell failure rat and can antagonize the hyperactive nerval endocrine system.

  7. Effect of calcium-activated neutral protease-2 on drug resistance of hepatocarcinoma cell to adriamycin%钙激活中性蛋白酶-2对肝癌细胞阿霉素耐药性的影响

    Institute of Scientific and Technical Information of China (English)

    徐国强; 唐佳艳; 向敏; 王艳; 洪阳; 胡晓霞; 王旭东; 陈腾祥

    2011-01-01

    目的 观察阿霉素作用下,钙激活中性蛋白酶-2(calpain-2)在肝癌细胞(HepG2)中的表达及其对细胞存活率的影响,评价其作为抗癌药靶的可能性.方法 以倍比稀释的ADM作用于HepG2细胞,用四甲基偶氮唑盐比色(MTT)实验检测阿霉素(Adriamycin,ADM)72 h的半数致死量(LD50);用蛋白质印迹(Western blot)检测的ADM(LD50)作用下,calpain-2和cyclin E的表达和酶解情况;给予calpain-2抑制剂(calpastatin peptide)干预后,用MTT法观察ADM对HepG2细胞存活率的影响.结果 MTT实验结果显示,ADM对HepG2的LD50为2.5 μmol·L-1;Western blot发现,随ADM作用时间的延长,calpain-2的表达水平增高(P<0.01),而且被剪切的程度增加(P<0.05);MTT检测ADM对HepG2的作用发现,calpastatin peptide干预的细胞存活率明显低于对照组(P<0.01),Cyclin E 被剪切的程度减轻(P<0.01).结论 肝癌细胞HepG2在ADM作用下发生凋亡的同时,也上调calpain-2的表达水平和活性,并通过其信号通路降低对ADM的敏感性,而针对calpain-2的活性抑制可以提高HepG2对ADM敏感性,提示calpain-2可以作为降低肿瘤化疗耐药性的潜在靶点.%Aim To explore the expression of calciumactivated neutral protease-2( calpain-2 ) in hepatocarcinoma cell ( HepC2 ), the effect on survival rate of HepG2 for evaluating potential value of calpain-2 as drug target. Methods Median lethal dose ( LD50 ) of HepG2 treated with different dosage adriamycin ( ADM ) for 72 h was evaluated with tetrazolium salt colorimetric method ( MTT ). The expression and zymohydrolysis of calpain-2 and cyclin E in HepG2 treated with ADM with LDso were detected with Western blot. The survival rates of HepG2 treated with ADM ( LD50 ) or companied with calpastatin peptide. inhibitor for calpain-2 , were tested with MTT. Results The LDso of ADM to HepG2 was 2. 5 μmol · L-1 as MTT result showing. Western blot showed that Calpain-2 was up-regulated ( P < 0. 05 )and cut into low molecular weight

  8. LDLr表达失衡在阿霉素肾病大鼠肾小球硬化中的作用%The Effects of Failure of Low Density Lipoprotein Receptor Expression During Glomerulosclerosis Secondary to Adriamycin-induced Nephrosis Rats

    Institute of Scientific and Technical Information of China (English)

    张伟; 张高福; 王莉; 李秋; 王莉佳; 杨锡强

    2014-01-01

    Objective:To observe the expression of low density lipoprotein receptor ( LDLr) , sterol regulatory element bind-ing protein-2 (SREBP-2) in kidney of glomerulosclerosis secondary to adriamycin (ADR) induced nephrosis rats, and the under-lying mechanism of lipid-mediated renal injury and renoprotective effect of statins. Methods:Male Sprague-Dawley rats were ran-domly divided into control, ADR nephrosis, and simvastatin-treated ADR nephrosis groups. After 12 weeks of therapy, the expres-sion of LDLr and SREBP-2 were detected by reverse transcription-polymerase chain reaction and Western-blot assay, the choles-terol in kidney was measured by enzymic colorimetric method and Oil red O staining, and glomerulosclerosis index ( GSI) was also e-valuated. Results:Compared with the control group, the expression of LDLr and SREBP-2, cholesterol in kidney and the GSI were all significantly increased in ADR nephrosis group (all P<0. 01). Treatment with simvastatin could significantly decrease the expres-sion of LDLr and SREBP-2, the accumulation of cholesterol in kidney and the GSI were also decreased (P<0. 05 or P<0. 01, re-spectively) . Linear Regression analysis showed that the accumulation of cholesterol in kidney was associated with the upregulation of LDLr and SREBP-2 (all P<0. 01). Conclusion:The effects of failure of LDLr expression may be responsible for the accumulation of cholesterol in kidney during glomerulosclerosis secondary to adriamycin-induced nephrosis rats, the renoprotective effect of simvasta-tin may attribute to decreasing the expression of LDLr.%目的:观察阿霉素肾病大鼠肾小球硬化过程中低密度脂蛋白受体( LDLr)的表达情况,及辛伐他汀对LDLr表达的影响,探讨LDLr在脂质导致肾病大鼠肾脏损害过程中的作用及他汀类药物肾脏保护的机制。方法:雄性SD大鼠随机分为正常对照组、阿霉素肾病组(模型组)和阿霉素肾病辛伐他汀治疗组(治疗组),12周后收集标本,光镜

  9. Bufalin alleviates adriamycin-induced podocyte injury by up-regulating the expression of vitamin D receptor%蟾蜍灵通过上调维生素D受体表达缓解阿霉素诱导的足细胞损伤

    Institute of Scientific and Technical Information of China (English)

    殷勤; 施会敏; 曲高婷; 张爱青; 甘卫华

    2016-01-01

    Objective To investigate the role of vitamin D receptor (VDR) in the protection of bufalin on podocyte injury induced by adriamycin (ADR).Methods (1) In vitro:the toxic effect of different concentrations of bufalin (10-9,10-8,10-7,104 mol/L) on podocyte was evaluated by lactate dehydrogenase (LDH) test;Annexin V-FITC and RT-PCR were utilized for podocyte apoptosis and VDR mRNA level respectively.Western blotting was used to analyze the protein expression of VDR and nephrin.SiRNA intervene was also applied to evaluate the role of VDR in bufalin's protective effect on podocyte injury induced by ADR.(2) In vitro:24 SD rats were randomly divided into three groups:control group,ADR group and ADR+bufalin group.TUNEL assay was applied to detect the apoptosis of podocytes in the kidney.Immunofluorescence and transmission electron microscope (TEM) were applied to analyze the expression of VDR and the ultrastructure of the glomerulus.Results Bufalin concentration lower than 10-7 mol/L had no toxicity on normal podocyte.Bufalin reduced the urinary protein excretion (P < 0.05),alleviated the removal of podocyte foot processes and attenuated the changes in nephrin expression in the glomerulus of the adriamycin (ADR) rats (P < 0.05).Bufalin notably inhibited the down-regulation of VDR in protein levels on the glomerulus of the ADR rats.Additionally,bufalin inhibited the down-regulation of VDR in both mRNA levels and protein levels (P < 0.05),nephrin protein expression (P< 0.05),and apoptosis induced by ADR in cultured podocytes.Additionally,VDR specific siRNA intervene abolished the protective effect of bufalin in ADR-induced podocyte injury.Conclusion Bufalin can alleviate ADR-induced podocyte injury via enhancing VDR expression.%目的 探讨维生素D受体(vitamin D receptor,VDR)在蟾蜍灵保护阿霉素诱导的足细胞损伤中的作用.方法 (1)体外实验:乳酸脱氢酶(LDH)释放试验观察不同浓度蟾蜍灵(10-9、10-8、10-7、10-6mol/L)对正常足

  10. Autologous mesenchymal stem cells transplantation in adriamycin-induced cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jing; LI Geng-shan; LI Guo-cao; ZHOU Qing; LI Wen-qiang; XU Hong-xin

    2005-01-01

    @@ Recent studies have suggested benefits of mesenchymal stem cells (MSCs) transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium, but its effects on global heart failure is still little known. This study suggested the capacity of MSCs to transdifferentiate to cardiac cells in a nonischemic cardiomyopathic setting, and the effect of the cells on heart function.

  11. 褐藻多糖硫酸酯对阿霉素肾病大鼠足细胞分子nephrin的影响%Effect of Sulfated Fucan on Nephrin Expression of Kidney of Rats with Adriamycin-induced Nephritic Syndrome

    Institute of Scientific and Technical Information of China (English)

    于春美; 杨淑玲; 吴汉利

    2013-01-01

    目的 本实验研究观察褐藻多糖硫酸酯(FPS)对阿霉素肾病大鼠肾脏nephrin表达的影响,并探讨其抗蛋白尿的分子机制.方法 采用尾静脉注射法建立阿霉素肾病模型,将实验动物随机分为正常组、模型组、苯那普利组、FPS组各10只.第4周末处死大鼠用半定量RT-PCR法检测肾皮质中nephrin mRNA;同时眼眶取血检测尿蛋白及血清白蛋白(ALB)、尿素氮(BUN)、肌酐(Scr)、总胆固醇(CHO)和甘油三酯(TG).观察一般情况及体质量.造模第0、14、28日24h蛋白尿.结果 与模型组相比,苯那普利组和FPS组24 h尿蛋白、血脂明显降低,同时nephrin mRNA表达显著提高;FPS组对第28日体质量、24h尿蛋白水平、ALB、CHO及TG改善明显优于苯那普利组(P< 0.05).结论 FPS可能是通过提高足细胞分子nephrin基因的表达治疗阿霉素肾病大鼠蛋白尿.%Objective:To research the impact and the mechanism of Sulfated fucan (FPS) on Adrianmycin-inducded nephritic syndrome in rats.Methods:40 female SD rats were divided randomly into the following groups:the normal group(n=10),the model group(n=10),the benazepril hydrochloride group(n=10) and the Sulfated fucan group (n=10).The nephritic syndrome modle was induced by etail intravenous injection of adriamycin in day 1.24 hours after the last administration of medicine,the expression of nephrin mRNA of the kidney tissues of rats were examined through RT-PCR.24 hours after the last administration of medieine,these indicators were detected such as Scr,Bun,ALB,TG and CHO.The general conditions and weight of body and the 24 hour urea protein quantity (24HUPQ) were checked at 0,14 and 28 days after the model had been made firstly.Results:On the 14th,28th day after the administration of medicine,24 HUPQ and CHO,TG of the treatment groups were significantly lower than those of the model group(P< 0.01).24 HUPQ of the FPS group was significantly lower than that of the the benazepril hydrochloride

  12. The short-term effect of the large dose of methotrexate,cisplatin combined with adriamycin in the chemotherapy of osteosarcoma%大剂量甲氨蝶呤、顺铂联合阿霉素新辅助化疗骨肉瘤的近期疗效分析

    Institute of Scientific and Technical Information of China (English)

    郑家雷; 方向; 汪子书

    2015-01-01

    目的:观察大剂量甲氨蝶呤( MTX)、顺铂( PDD)联合阿霉素( ADR)新辅助化疗骨肉瘤的近期疗效及不良反应. 方法:选择经过组织病理学及影像学诊断、有客观评价指标、初治的ⅡB期肢体骨肉瘤患者30例作为研究对象,化疗方案均为大剂量MTX、PDD 联合ADR,21 d为1周期,3~4个周期复查病变部位MRI及平片后行人工关节置换术或截肢术,根据术后骨肉瘤的病理学检查肿瘤组织坏死率及保肢成功率评价疗效. 结果:术后骨肉瘤病理学检查肿瘤组织坏死率>90%的患者占86. 7%,保肢成功为53. 0%. 不良反应中恶心呕吐、脱发和中性粒细胞减少发生率均为100. 0%(30/30),血红蛋白降低率为86. 7%,白细胞升高率16. 7%,口腔肠道黏膜炎发生率26. 7%,肝功能损害率13. 3%. 结论:大剂量MTX、PDD联合ADR新辅助化疗骨肉瘤患者术后病理学检查肿瘤组织坏死率高,保肢成功率高,近期疗效肯定,不良反应可耐受,值得推广使用.%Objective:To investigate the short-term effects and adverse reactions of the large dose of methotrexate(MTX),cisplatin (PPD) combined with adriamycin(ADR) in the chemotherapy of osteosarcoma. Methods:Thirty extremity osteosarcoma patients(ⅡB phase) diagnosed by histopathology and imaging were investigated. All patients were treated with the high dose of MTX,PDD combined with ADR,21 days for a cycle. The artificial joint replacement or amputation were implemented according to the MRI and plain film of lesions after 3 to 4 cycles of treatment. The curative effects were evaluated by the salvage success rate and tumor tissue necrosis rate according to the postoperative osteosarcoma pathological examination. Results:The tumor necrosis in more than 90% patients was identified by the result of postoperative pathological examination of osteosarcoma,the rates of tumor necrosis and salvage success were 86. 7% and 53. 0%,respectively. All the incidences of nausea and vomiting

  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. 霉酚酸酯对阿霉素肾病大鼠肾小球Nephrin和TGF-β1表达的影响%Effects of mycophenolate mofetil on the renal Nephrin and transforming growth factor-β1 of adriamycin nephritic rats

    Institute of Scientific and Technical Information of China (English)

    王军建; 李少宁; 林菲; 王列

    2013-01-01

    Objective: To explore effects of Mycophenolate mofetil on expression changes of Nephrin and transforming growth factor-β1 (TGF-β1) in adriamycin(ADR) induced nephropathy rats. Methods:Thirty six rats of Sprague Dawley were divided into two groups: the model group (n = 24) and the control group (n = 12). The rats in the model group were injected with a single dose of ADR ( 7 mg /kg ) via tail vein, while the rats in the con tro1 group were injected with a comparable volume of 0. 9% saline. The model was successfully established when the 24 h urinary protein excretion exceeded 100 mg after ADR injection 1 week, Twenty rats were successful and then were randomly assigned to the ADR nephrosis group (n = 10) and the MMF group(n = 10). The rats in the MMF group were treated with MMF (10 mg/ kg /d ) I g,once a day for 8 weeks,whereas the other rats were received a comparable volume of 0. 9% saline. The 24 h urinary protein excretion was measured and the pathological changes of the renal tissues were observed under light microscope, Immunohistochemical and Western Blotting techniques to de tect the expression of Nephrin and TGF-β1. Results: The 24 h urinary protein and the expression of TGF-β1 in the ADR nephrosis group were higher than those in the control group and MMF group (P100 mg/24h即为建模成功,共有20只大鼠建模成功,随机又分为肾病模型组(n = 10)和MMF干预组(n = 10).MMF干预组每天给予MMF 10 mg/ kg灌胃,每日1次,共8周.对照组和肾病模型组给予等容积生理盐水灌胃.实验结束后检测各组大鼠24 h尿蛋白定量,光镜观察肾脏病理学改变,免疫组化技术和Western-Blotting技术检测Nephrin、TGF-β1的表达.结果:肾病模型组及MMF干预组24 h尿蛋白定量、肾小球TGF-β1表达均高于对照组(P<0.05),但MMF干预组上述指标均低于肾病模型组(P<0.05);肾病模型组及MMF干预组肾小球Nephrin表达低于对照组(P<0.05),但MMF干预组Nephrin

  15. Study on calcium homeostasis disorders of adriamycin resistant human breast cancer cells MCF-7/ADM and its mechanism%耐阿霉素人乳腺癌细胞MCF-7/ADM钙稳态失调及其机制研究

    Institute of Scientific and Technical Information of China (English)

    蔡燕飞; 陈蕴; 朱瑞宇; 马鑫; 姚晓强; 金坚

    2013-01-01

    目的 探讨耐阿霉素人乳腺癌细胞MCF-7/ADM钙稳态失调及其机制.方法 转染指示钙离子质粒GECO1.2,检测野生型和耐药型细胞中的[Ca2+]含量;通过Western blot检测瞬时受体电位离子通道(transient receptor potential channel)蛋白TRPC1、TRPC3、TRPC4、TRPC5和TRPC6在两种细胞中的表达情况;运用钙离子通道抑制剂2-APB(100μmol·L-1)抑制耐药细胞中高表达的TRPC5活性后,检测耐药细胞中的[Ca2+]含量.结果 耐药细胞中的[Ca2+]含量明显上调,并检测到TRPC5蛋白在耐药细胞中发生高表达,其活性被抑制后,耐药细胞中的[Ca2+]浓度发生下调.结论 与野生型细胞相比,耐药细胞中钙稳态失调,其原因可能是由于耐药细胞中TRPC5表达上调引起耐药细胞中[Ca2+]内流所致.提示钙稳态失调与肿瘤细胞的耐药发生有着密切关系.%Aim To investigate the calcium homeostasis disorders of adriamycin-resistant human breast cancer cells MCF-7/ADM and its mechanism. Methods Detect the ( [ Ca2+ ] ) content of wild-type and drug-resistant cells by the transformation of calcium indicator plasmid GEC01.2; Detect the expression of transient receptor potential ion channel protein TRPC1 , TRPC3 , TRPC4 , TRPC5 and TRPC6 in these two cells by Western blot; Suppress the TRPC5 activity with calcium channel inhibitor 2-APB (100 μmol · L-1 ), and then detect the ( [ Ca2+] ) content in the drug-resistant cells. Results The result shows that the significantly up-regulation of ( [ Ca2+ ] ) content in resistant cells,and the TRPC5 protein shows over-expression, but the ( [ Ca2+] ) concentration became to decrease after the inhibition of its activity. Conclusion Compared with the wild-type cells, the calcium in resistant cells became homeostasis disorder, maybe the underlying mechanism is the up-regulation of TRPC5 caused [ Ca2+ ] entry into the resistant cells. This study suggests that there must be a close relationship between calcium homeostasis

  16. 胡椒碱对乳腺癌阿霉素耐药细胞株 MCF -7/ADM 细胞的逆转作用%Reversal Effect of Piperine on Adriamycin - Resistant MCF - 7/ADM Cells of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    赖艳; 温悦; 卢来春

    2014-01-01

    Objective To explore the reversal effect and mechanism of piperine on the multidrug adriamycin(ADM) - resistance cell line MCF - 7 / ADM of human breast cancer. Methods The effect of piperine combined with ADM on growth and proliferation of drug - re-sistant MCF - 7 / ADM cells were observed by using the CCK - 8 assay. The expression levels of P - glycoprotein (P - gp) in MCF - 7 / ADM cells treated with piperine were detected by Western blot. Results The drug resistance reversal fold in the experimental groups with 60,80,100 μmol / L of piperine was 1. 62,2. 08,3. 78 times respectively. Piperine could significantly inhibit the expression of P - gp on the cytomembrane of MCF - 7 / ADM cells and enhanced the cellular sensitivity to ADM. Conclusion Piperine and adriamyci co - acting on MCF - 7 / ADM cells can increase the cellular sensitivity to ADM. Piperine can partially induce the reversal of drug resistance of MCF - 7 / ADM cells, its mechanism may be related with the down - regulation of the P - gp expression.%目的:探讨胡椒碱对人乳腺癌阿霉素(ADM)耐药细胞株 MCF -7/ ADM 的逆转作用及其机制。方法采用 CCK -8法观察胡椒碱联合阿霉素(ADM)对乳腺癌耐药株 MCF -7/ ADM 细胞生长增殖的影响;应用免疫印迹技术(Western - blot)测定胡椒碱联合 ADM 对MCF -7/ ADM 细胞表面 P -糖蛋白(P - gp)表达的影响。结果60,80,100μmol / L 胡椒碱试验组细胞耐药逆转倍数分别为1.62,2.08,3.78倍,差异有统计学意义( P ﹤0.05)。胡椒碱能显著抑制 MCF -7/ ADM 细胞膜 P - gp 蛋白的表达,其作用随浓度的增加而增强。结论胡椒碱与 ADM 共同作用于 MCF -7/ ADM 细胞,可使细胞对 ADM 的敏感性增强。胡椒碱具有部分逆转 MCF -7/ ADM 细胞耐药的作用,其逆转作用机制可能与通过下调 P - gp 的表达有关。

  17. Basic experimental research on methylene blue-mediated photody-namic therapy combined with adriamycin for breast carcinoma%亚甲蓝光动力疗法联合阿霉素治疗乳腺癌的实验研究*

    Institute of Scientific and Technical Information of China (English)

    佟仲生; 刘晓东; 史业辉; 李淑芬; 王忱; 郝春芳

    2013-01-01

      目的:探讨亚甲蓝介导的光动力疗法联合阿霉素对小鼠乳腺癌细胞系4T1的体外及体内抑瘤效应及其相关机制,为临床应用提供理论依据。方法:本研究分为空白对照组、阿霉素组、光动力治疗组及联合治疗组。MTT法检测光动力疗法联合阿霉素对乳腺癌细胞增殖的影响。流式细胞术检测细胞凋亡及坏死情况。Rhodamine123检测线粒体膜电位变化。建立乳腺癌荷瘤小鼠模型,绘制肿瘤生长曲线,观察治疗效果。结果:体外实验表明光动力疗效与光敏剂呈剂量依赖性,而联合阿霉素可以增强抑瘤效应。阿霉素组细胞死亡率较低,光动力治疗组以早期及晚期凋亡为主,联合治疗组以晚期凋亡及坏死为主。与空白对照组比较,光动力治疗组及联合治疗组线粒体膜电位显著降低,差异均有统计学意义(P<0.05),联合治疗组较光动力治疗组线粒体膜电位更低(P<0.05)。体内实验显示光动力疗法可以显著抑制小鼠乳腺癌皮下移植瘤生长,而联合阿霉素可以增强抑瘤作用。结论:亚甲蓝介导的光动力疗法对乳腺癌细胞及移植瘤的生长抑制作用明显,联合阿霉素可增强抑瘤效果。光动力疗法以细胞凋亡为主,其机制可能与降低肿瘤细胞线粒体膜电位相关。%  Objective: This work aimed to investigate the therapeutic efficacy of methylene blue (MB)-mediated photodynamic therapy (PDT) with adriamycin (ADM) on 4T1 mouse mammary carcinoma cells in vitro and in vitro, thereby providing a theoretical ba-sis for clinical applications. Methods: The experimental study was divided into four groups, namely, control (Group One), ADM (Group Two), PDT (Group Three), and therapeutic alliance or PDT+ADM (Group Four). Methyl thiazolyl tetrazolium assay was em-ployed to determine the effects of the combined therapy on the proliferation of breast cancer cells. Cell

  18. 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

  19. 实脾固肾化瘀方对阿霉素肾纤维化大鼠肾组织I型胶原蛋白、转化生长因子β1、层黏连蛋白及α平滑肌肌动蛋白表达的影响%Effects ofShipi-Gushen-HuayuRecipe on the expressions of collagen I, laminin, transforming growth factor-β1 andα-smooth muscle actin in adriamycin-induced renal fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    王高强; 沈丽萍; 张玮; 李珺; 倪家庆; 米秀华

    2014-01-01

    Objective To investigate the effects ofShipi-Gushen-Huayu Recipe on the expressions of collagen I, laminin(LN), transforming growth factor-β1(TGF-β1)andα-smooth muscle actin(α-SMA)in adriamycin-induced renal fibrosis in rats.Methods A total of male SD rats were randomly divided into four groups, with 10 rats in each group: a normal group, a model group, a treatment group and a fosinopril sodium group. Except the rats in the normal group, the rest rats were subjected to renal fibrosisvia tail intravenous injection of adriamycin(4 mg/kg). Two weeks after modeling, the rats in the rreatment group and in the fosinopril sodium group were intragastrically administrated daily withShipi-Gushen-Huayu Recipe extract(43 g/kg)and fosinopril solution(2 mg/kg), respectively,both in the normal group and model group with saline. After 30 days, 24-hours urine protein were determined, and the expressions of collagen I, LN, TGF-β1 andα-SMA in kidney tissue were detected with immunohistochemistry staining.Results The expressions of collagen I(24.64±0.67vs. 32.86±0.88), LN(18.71±0.72vs. 28.35±0.87), TGF-β1(14.71±0.68vs. 18.35±0.96)andα-SMA(17.64±0.74vs. 25.86±0.85)in the treatment group were significantly lower than those in the model group(allP<0.01). The expressions of collagen I, LN, TGF-β1 andα-SMA in the fosinopril sodium group were 27.33±0.73, 20.44±0.81, 15.44±0.85 and 19.33±0.77, respectively. There was no statistically significant difference between the expressions of collagen I, LN, TGF-β1 andα-SMA in the treatment group and in the fosinopril sodium group.ConclusionShipi-Gushen-Huayu Recipe can significantly down regulate the expressions of collagen I, LN, TGF-β1 andα-SMA in adriamycin-induced renal fibrosis in rats.%目的:观察实脾固肾化瘀方对阿霉素诱导肾纤维化大鼠I型胶原蛋白、转化生长因子β1(TGF-β1)、层黏连蛋白(LN)及α-平滑肌肌动蛋白(α-SMA)表达的影响。方法40只

  20. 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.

  1. Electrochemical Behavior of Adriamycin at Ni/GC Ion Implantation Modified Electrode

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    With a Ni/GC ion implantation modified electrode as working electrode, in 0.1 mol/L HOAc-NaOAc (pH=4.62) solution, a sensitive reductive wave of ADM was obtained by linear sweep voltammetry. The peak potential was -0.55 V (vs.SCE). The peak current is proportional to the concentration of ADM with a detection limit of 6.9×10-8 mol/L. The behavior of the reduction wave was studied. The experiments of AES and XPS showed that Ni was surely implanted into the surface of the GCE and the implanted Ni at the GCE improved the electrocatalytic activity.

  2. Influence of docosahexaenoic acid in vitro on intracellular adriamycin concentration in lymphocytes and human adriamycin-sensitive and -resistant small-cell lung cancer cell lines, and on cytotoxicity in the tumor cell lines

    NARCIS (Netherlands)

    Zijlstra, J G; de Vries, E G; Muskiet, F A; Martini, I A; Timmer-Bosscha, H; Mulder, N H

    1987-01-01

    An increase in the therapeutic effects of cancer chemotherapeutic agents and circumvention of drug resistance in cancer cells might result from an increase in the intracellular drug level. Alteration of the lipid domain of the cell membrane can result in a higher intracellular drug level. This alter

  3. Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors

    NARCIS (Netherlands)

    de Jong, Steven; Holtrop, M; de Vries, H; de Vries, Liesbeth; Mulder, N H

    1992-01-01

    The energy metabolism of an atypical multidrug resistant human small cell lung carcinoma cell line (GLC4/ADR) was studied. The glycolytic rate was 30% reduced and the glucose-6-phosphate dehydrogenase activity 2-fold increased in GLC4/ADR compared to the parental sensitive line (GLC4). Although mito

  4. Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

    Directory of Open Access Journals (Sweden)

    Yanbo Liu

    2015-07-01

    Full Text Available Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

  5. THE AMPLIFICATION AND EXPRESSION OF MDR1 GENE IN ADRIAMYCINE RESISTANT CELL LINE OF COLON CANCER CELL HR8348

    Institute of Scientific and Technical Information of China (English)

    周中军; 罗贤懋; 林晨; 陈凤

    1996-01-01

    P-glycoprotein plays an important role in highly drug resistant cells. But its high expression cannot be acheived by chemotherapy. In order to study the effect of P-glycoprotein on clinical tumors, wo ostablished a low ADM resistant colon cancer ceil line HR/ADM and determined the amplification and expression of mdr-1 gene. The GLC/ADM showed a resistant pattern similar to classical MDR and the transcription of mdr-1 gene determined by RT-PCR increased. The immunocytcchemical analysis showed strong positive staining with monoelonal antibozly. The gene amplification of mdr-l was dearly demonstrated by southern blot. Our results suggested that moderate expression of P-glycoprotein might be enough for a high resistant pattern.

  6. Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat

    NARCIS (Netherlands)

    Ochodnicky, Peter; Mesarosova, Lucia; Cernecka, Hana; Klimas, Jan; Krenek, Peter; Goris, Maaike; van Dokkum, Richard P. E.; Henning, Robert H.; Kyselovic, Jan

    2014-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular an

  7. 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)

  8. Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Rook, M; Lely, AT; Kramer, AB; van Goor, H; Navis, G

    2005-01-01

    Background. In man, differences in angiotensin converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we stud

  9. Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Rook, Mieneke; Lely, A Titia; Kramer, Andrea B; van Goor, Harry; Navis, Gerjan; van Goor, Harm

    2005-01-01

    BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we stud

  10. The Study on the Relationship between Serum Vascular Endothelial Growth Factor and Proteinuria in Adriamycin-induced Nephrotic Rats

    Institute of Scientific and Technical Information of China (English)

    ZHU; Zhonghua(

    2001-01-01

    [1]Carmeliet P Collen D.Molecular analysis of blood vessel formation and disease.Am J Physiol 1997 273 :H2091[2]Gleade J M Ebert B L Firth J D.Regulation of angiogenic growth factor expression by hypoxia transition metals and chelating agents.Am J Physiol 1995 268:C1362[3]Uchida K Uchida S.Glomerular endothelial cells in culture express and secrete vascular endothelial growth factor.AmJPhysiol 1994 266:F240[4]Simon M Grone H J Johren O.Expression of vascular endotheial growth factor and its receptors in human renal ontogenetis and adult kidney.Am J Physiol 1995 268:F81[5]Bailey E Bottomley M J.Vascular endothelial growth factor mRNA expression in minimal change membranous and diabetic nephrothy demonstrated by non-isotopic in situ hybridization.J Clin Pathol 1999 52:735[6]Nicholas J A Webb N J Waston C J.Circulation vascular endotheial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome.Kidney Int 1999 55:1063[7]Shulman K Rosen S Tognazzi K.Expression of VPF is altered in many glomerulous disease.J Am Soc Nephrol 1996 7:661

  11. Inter-individual differences in anti-proteinuric response to ACE in established adriamycin nephrotic rats are predicted by pretreatment renal damage

    NARCIS (Netherlands)

    Kramer, A.B.; Laverman, Ger Jan; van Goor, H.; Navis, Ger Jan

    2003-01-01

    ACE inhibition (ACEi) reduces proteinuria and provides reno-protection, but not all subjects benefit from ACEi. Individual differences in the reduction in proteinuria at the onset of treatment and in residual proteinuria during therapy predict differences in renal outcome. The present study investig

  12. 罗格列酮减轻阿霉素肾病大鼠肾小球硬化的实验观察%Experimental observation of rosiglitazone on ameliorating adriamycin-induced glomerulo sclerosis

    Institute of Scientific and Technical Information of China (English)

    苏雪松; 周光宇; 李德天

    2005-01-01

    目的 观察罗格列酮干预治疗对单侧肾切除加重复阿霉素注射诱导的肾小球硬化大鼠肾脏的保护作用.方法 建立单侧肾切除加重复阿霉素注射的肾小球硬化大鼠模型,分为罗格列酮治疗组和肾病组,设假手术组为对照组.检测各组大鼠第0、4、8、12周尿蛋白,并观察第12周肾组织病理改变,计算肾小球硬化指数.结果 罗格列酮治疗组比肾病组尿蛋白排泄量明显减少(P<0.01),肾小球硬化程度明显减轻.结论 罗格列酮对阿霉素肾病大鼠肾脏病变具有保护作用.

  13. 后肾间充质细胞移植治疗大鼠慢性阿霉素肾病%Treatment of metanephric mesenchymal cells transplantation for adriamycin-induced chronic nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    焦玉清; 莫双红; 易著文; 何小解; 刘喜红; 何庆南; 黄丹琳; 党西强; 吴小川; 曹艳

    2009-01-01

    目的 探讨大鼠胚胎后肾间充质细胞(MMC)尾静脉移植对慢性阿霉素(ADR)肾病大鼠的治疗作用.方法 90只雌性SD大鼠被随机分为阿霉素.肾病组(n=40,间隔3周2次尾静脉注射阿霉素0.25 mg/100 g)、MMC移植组(n:40,于第2次阿霉素注射后8周,尾静脉注射5×10~6-7×10~6 MMC)、对照组(n=10).于细胞移植后第8周杀鼠,留取肾组织行病理学分析;免疫组织化学检测肾组织Ⅳ型胶原、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP.9)的表达;Western印迹及RT-PCR分别对MMP-2、MMP-9的蛋门及基因表达进行半定量检测.结果 MMC移植组和阿霉素肾病组肾小管损伤指数及肾小球硬化而积差异无统计学意义(P>0.05).与阿霉素肾病且比较,细胞移植组肾组织Ⅳ型胶原沉积减少,MMP-2蛋白及基因表达下调,MMP-9蛋白及基因表达升高,差异均有统计学意义(均P0.05).Compared with ADR group,collagen Ⅳ and MMP-2 expression decreased, MMP-9 expression incrased in renal tissue of ADR-MMCs group, and the difference was significant (P<0.05). Conclusion MMCs transplantation may have potentially therapeutic effect on renal tissue fibrosis of adriamyein-induced glomerulopathy in rats, and the signaling pathways of MMPs appear to be involved in these processes.

  14. 1,25-(OH)2D3增加阿霉素肾病大鼠CD2AP表达%1,25-Dihydroxyvitamin D3 increase the expression of CD2AP in adriamycin nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    邹敏书; 余健; 聂国明; 何威逊

    2007-01-01

    目的 观察1,25-(OH)2D3对阿霉素肾病大鼠肾小球CD2AP表达的影响.方法 Wistar大鼠随机分为对照组和阿霉素模型组,后者经尾静脉注射阿霉素(ADR)诱导肾病模型,再随机分肾病组和1,25-(OH)2D3组.实验5周末测定大鼠尿蛋白、相关生化指标及电解质.肾小球CD2AP免疫组化及荧光染色分析肾小球CD2AP蛋白的表达.多元回归分析CD2AP的平均吸光度值(A)与上述检测指标的关系.结果 与对照组相比,肾病组大鼠尿红细胞、尿蛋白、胆固醇(TC)、甘油三酯(TG)、甲状旁腺素(PTH)明显升高(P<0.01),血清白蛋白(Alb)、1,25-(OH)2D3、离子钙(Ca2+)降低(P<0.05或P%0.01),磷(P)无明显差异(P>0.05),CD2AP蛋白表达明显下调(P<0.01).与肾病组相比,1,25-(OH)3D3组尿红细胞、尿蛋白、TC、TG、PTH下降(P<0.05或P<0.01).而Alb,1,25-(OH)2D3、Cd2+增加(P%0.01).P无明显差异(P>0.05),CD2AP蛋白表达明显增加(P<0.01).多元回归分析显示,A值与尿蛋白呈负相关(rs=-0.63,P<0.01),与1,25-(0H)2D3、Alb水平正相关(rs=0.59、0.27,P%0.05).结论 1,25-(OH)2D3可减轻ADR肾病大鼠血尿、蛋白尿,调节血脂及钙磷代谢障碍,恢复CD2AP蛋白的表达,具有保护肾脏作用.

  15. The protective effects of oxymatrine against adriamycin-induced cardiotoxicity in rabbits%氧化苦参碱对阿霉素心脏毒性的影响

    Institute of Scientific and Technical Information of China (English)

    马飞; 李小平; 俞炬明; 郑磊贞

    2007-01-01

    目的:观察氧化苦参碱(oxymatrine,OMT)在动物实验中对阿霉素(ADR)所致心脏毒性的保护作用.方法:26只新西兰大白兔随机分为4组:ADR组(8只)、ADR+OMT组(8只)、生理盐水组(5只)、OMT组(5只).实验兔每周耳缘静脉注射ADR(2 mg/kg)1次,共8周,制备慢性心肌损伤模型.OMT(10 mg/kg)于ADR应用前30 min经耳缘静脉注射.用药前和停药3周后左颈总动脉及左室插管测定左室射血分数(LVEF)、左心室收缩压(LVSP)和左心室舒张末压(LVEDP);取血测定血液中乳酸脱氢酶(LDH)和肌酸磷酸激酶(CK-MB)活性.停药3周后,电镜观察心肌细胞超微结构变化.结果:ADR组中LVEF、LVSP明显降低,LVEDP明显升高,LDH和CK-MB活力显著升高.ADR+OMT组也有相似改变,程度较轻,两组之间差异有统计学意义.ADR组和ADR+OMT组均有心肌超微结构损伤,但ADR+OMT组病变程度明显轻于ADR组.OMT组动物未观察到任何不良反应和病理变化.结论:氧化苦参碱对阿霉素致心肌损伤具有保护作用.

  16. 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.

  17. The effect of sodium phosphocreatine on the endoplasmic reticulum stress signal pathway of adriamycin-injured cardiomyocytes that Calumenin silencing by shRNA%磷酸肌酸钠对慢病毒介导Calumenin蛋白沉默阿霉素损伤心肌细胞内质网应激信号通路的作用

    Institute of Scientific and Technical Information of China (English)

    王伊林; 赵雅君; 杨洋; 柴花; 黄侠; 赵明

    2015-01-01

    目的:探讨磷酸肌酸钠对网腔钙结合蛋白(Calumenin)沉默阿霉素损伤心肌细胞内质网应激信号通路作用.方法:培养乳鼠心肌细胞,构建稳定的慢病毒——Calumenin质粒,转染乳鼠培养心肌细胞,实验分为4组:对照组(正常细胞+3 mg/L阿霉素)、模型组(慢病毒感染细胞+3 mg/L阿霉素)、磷酸肌酸钠1组(正常细胞+阿霉素+磷酸肌酸钠)、磷酸肌酸钠2组(转染细胞+阿霉素+磷酸肌酸钠).采用Western blotting技术检测各组心肌细胞Calumenin蛋白、内质网应激伴侣蛋白GRP78及内质网应激信号通路因子PERK、PATF-4PERK、eIF2a、ATe-4、IRE1、CHOP表达.结果:①与对照组比较,模型组及磷酸肌酸钠2组心肌细胞Calumenin蛋白表达明显减少(P<0.01).②与对照组相比,模型组内质网应激伴侣蛋白GRP78及内质网应激信号通路因子P-PERK、eIF2a、ATF-4、IRE1、CHOP表达明显增多(P<0.01).③与模型组相比较,磷酸肌酸钠1组及磷酸肌酸钠2组内质网应激伴侣蛋白GRP78及内质网应激信号通路因子P-PERK 、eIF2a、ATF-4、IRE1、CHOP表达减少(P<0.01).结论:阿霉素损伤可能诱发ERS,并通过ERS凋亡信号通路PERK→ P-PERK→ eIF2 a→ ATF-4→CHOP/IRE1→CHOP引起心肌细胞凋亡;磷酸肌酸钠可抑制阿霉素损伤所诱导内质网应激介导的心肌细胞凋亡,这一作用机制可能是通过Calumenin蛋白抑制ERS及其凋亡信号通路PERK→ P-PERK→ eIF2a→ ATF-4→CHOP/IRE1→CHOP实现的.

  18. Ginsenosides-Rbl improves adriamycin-induced heart failure by adjusting the protein kinase R-like ER kinase pathway%人参皂甙Rbl对心力衰竭大鼠蛋白激酶R样内质网激酶途径的影响

    Institute of Scientific and Technical Information of China (English)

    孔宏亮; 侯爱洁; 郭翠艳; 王俊丰

    2013-01-01

    目的 探讨人参皂甙Rbl (Gs-Rb1)改善阿霉素所致心力衰竭(HF)效应是否与调整蛋白激酶R样内质网激酶(PERK)通路有关.方法 阿霉素(Adr)诱导的HF大鼠随机分为HF组(n=15)和Gs-Rbl组(70 mg/kg/d,n=17),另随机选取同龄大鼠作为对照组(n=10).干预结束并进行心脏超声检查后,TUNNEL检测心肌细胞凋亡率(AR),Western blot和Rt-PCR检测葡萄糖调节蛋白78 (GRP78)、PERK、p-PERK、真核细胞起始因子2α(eIF2α)、p-eIF2α、C/EBP同源蛋白(CHOP)和cleaved caspase-12.结果 1.Adr干预成功构建HF模型,Gs-Rb1显著提高左室射血分数(LVEF)和降低心肌细胞AR (P<0.01);2.HF组GRP78 mRNA和蛋白均显著高于对照组,Gs-Rb1显著低于HF组和对照组二组的表达(P<0.01);3.Gs-Rb1显著降低HF大鼠PERK和p-PERK表达(P<0.01);4.HF导致eIF2α mRNA和蛋白、p-eIF2α显著升高,Gs-Rb1显著下调三者的表达(P<0.01);5.HF组CHOP mRNA和蛋白显著高于对照组,Gs-Rb1组显著抑制其表达(P<0.01);6.Gs-Rb1显著抑制阿霉素所致的caspase-12 mRNA和cleaved caspase-12蛋白表达 (P<0.01).结论 Gs-Rb1通过调节PERK内质网通路介导其改善HF效应.

  19. 阿霉素肾病大鼠肾小球中基质金属蛋白酶-2和基质金属蛋白酶组织抑制剂-2的表达%Expression of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-2 in glomerular of adriamycin-induced nephrotic rats

    Institute of Scientific and Technical Information of China (English)

    秦娜; 李广波; 林瑞霞; 杨青; 陈敏广; 郭树霞

    2011-01-01

    目的 探讨基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶组织抑制剂-2(TIMP-2)在阿霉素肾病大鼠中的表达和意义.方法 25只Sprague-Dawlay(SD)雄性大鼠,随机分为对照组10只和观察组15只,观察组尾静脉内一次性注射阿霉素7.5 mg·kg-1(以生理盐水稀释至3 mL),对照组尾静脉内一次性注射等量生理盐水,对照组和观察组每日1次按10 mL·kg-1给予生理盐水灌胃,灌胃共8周.采用反转录聚合酶链式反应法检测肾组织MMP-2和TIMP-2 mRNA的表达.结果 实验8周时与对照组比较,观察组的24 h尿蛋白定量、肌酐和尿素氮水平均显著上升(P<0.01),血白蛋白显著降低(P<0.01).对照组大鼠肾皮质区肾小球毛细血管襻开放较好,无细胞外基质(ECM)聚集;观察组大鼠肾组织可见部分毛细血管腔变窄甚至完全闭塞,肾小囊扩张,囊壁增厚,球囊粘连.观察组MMP-2和TIMP-2 mRNA的表达较对照组明显下降(P<0.01),观察组中MMP-2/TIMP-2 mRNA半定量比值较对照组明显降低(P<0.01).结论 MMP-2和TIMP-2在阿霉素肾病大鼠肾小球硬化中起到重要的作用;MMP-2/TIMP-2的比值失调使肾小球ECM降解减少,导致ECM过度积聚,参与肾小球硬化的发生发展.%Objective To explore the mechanism and effect of Escherichia coli( E. coli) infection on apoptosis of U937 cell in human macrophagic system. Methods U937 cells and E. coli were putted into culture media 0,10,20 ,30,60 and 90 minutes when the concentration ratio of them was adjusted to 1 : 20, then the infected U937 cells were found. The rates of U937 apoptosis in different time were detected by the flow cytometer. The expressive levels of caspase second mitochondrial ac tivator factor ( Smac) in cytoplasm of U937 cells and X chromosome linked inhibitor of apoptosis protein ( XIAP) were detec ted by Western blot. U937 cells were pretreated by Embelin which concentration were 0,10.20 and 40 μmol · L-1 at sixty mi nutes before the E. coli infection , and then U937 cells were gathered at thirty minutes after apoptosis induced by E. coli. The U937 cells apoptosis were analyzed by flow cytometer after Annexin V FITC/PI double-dyeing. Results When U937 cells : E. coli equaled to 1 : 20 , the apoptosis rates of U937 cells showed time-dependent, the apoptosis rates at 0 , 10.20 ,30 .60 and 90 minutes after infection were (3. 02 ±0. 78 ) %, ( 6. 67 ± 1. 34 )% , ( 10. 56 ± 1. 02) %, ( 33. 92 ± 2. 66)% , ( 46. 98 ± 3. 12)% and (69. 02 ±4. 69) %. U937 cells began to apoptosis after infected by E. coli,and the apoptosis rate was increased as the infected time extended. With the extension of E. coli infection's time , the expression of Smac was raised gradually , where as,the expression of XIAP was decreased gradually. Moreover, there were significant differences among different infected time ( P < 0. 05 ) . The apoptosis rate of U937 cells was increased gradually with the increasing of Embelin's concentration after pui ting into inhibitor Embelin( P <0. 05) . Conclusion U937 cells in human macrophage system began to apoptosis after infec ted by E. coli,and the occurrence and the influence of apoptosis were concemed with expression of Smac and XIAP. Through inhihit the expression of XIAP specifically,the Embelin increased the apoptosis rate of U937 cells after induced by E. coli. Cell in human macrophagic system. Methods U937 cells and E. coli were putted into culture media 0,10,20 ,30,60 and 90 minutes when the concentration ratio of them was adjusted to 1 : 20, then the infected U937 cells were found. The rates of U937 apoptosis in different time were detected by the flow cytometer. The expressive levels of caspase second mitochondrial ac tivator factor ( Smac) in cytoplasm of U937 cells and X chromosome linked inhibitor of apoptosis protein ( XIAP) were detec ted by Western blot. U937 cells were pretreated by Embelin which concentration were 0,10.20 and 40 μmol · L-1 at sixty mi nutes before the E. coli infection , and then U937 cells were gathered at thirty minutes after apoptosis i

  20. Changes of hTERT mRNA during the process of multidrug resistance by adriamycin in human colon carcinoma LoVo cells%阿霉素诱导大肠癌LoVo细胞产生多药耐药中端粒酶逆转录酶的变化

    Institute of Scientific and Technical Information of China (English)

    马强; 张方信; 康生朝; 陈嘉屿

    2006-01-01

    目的:观察在阿霉素诱导大肠癌LoVo细胞产生多药耐药过程中,端粒酶逆转录酶基因表达,明确端粒酶是否参与了多药耐药机制. 方法:采用阿霉素浓度递增法,建立人大肠癌细胞多药耐药模型LoVo/Adr;用MTT法鉴定耐药LoVo/Adr细胞的耐药性;以流式细胞术检测其周期分布;用RT-PCR方法检测hTERT mRNA水平在诱导耐药过程中的变化. 结果:历经8 mo+、传代67次连续培养,建立了人大肠癌耐药模型LoVo/Adr细胞株;LoVo/Adr对阿霉素、长春新碱、丝裂霉素、环磷酰胺和5-氟尿嘧啶耐药倍数分别是61倍、14倍、3倍、9倍和1倍;LoVo/Adr细胞与LoVo细胞相比,S期细胞减少,而G1, G2期增多;亲本LoVo细胞的hTERT mRNA呈低水平表达,在阿霉素诱导初期即显著增高,随后基本保持高表达状态,并不随着耐药性增加而增强. 结论:耐药株LoVo/Adr是一个典型的具有多药耐药性表型的耐药模型,端粒酶参与了其耐药机制.

  1. Tween-80并温热对人膀胱癌EJ/ADM的耐药逆转及作用机制%Reversal of drug resistance in the Adriamycin-resistant human bladder cancer cell lines EJ/ADM by Tween-80 in combination with hyperthermia, and its mechanism

    Institute of Scientific and Technical Information of China (English)

    刘迪; 朱玉芬

    2009-01-01

    目的 观察Tween-80合并温热对人膀胱癌阿霉素耐药细胞株的逆转作用及其机制.方法 采用MTT法进行体外药物逆转实验,免疫细胞化学染色显示处理前后耐药细胞P-糖蛋白表达情况.结果 ①Yrween-80合并41℃温热作用前后,EJ/ADM对抗癌药物阿霉素、丝裂霉素、5-氟尿嘧啶等药物的敏感性显著增加(P<0.01);②Tween-80合并41℃温热能够协同抑制p-gp蛋白的表达.结论 Tween-80合并41℃温热对人膀胱癌阿霉素耐药细胞的耐药性有逆转作用,逆转机制与其抑制p-gp蛋白的表达有关.

  2. 重组腺病毒p53联用阿霉素对肺鳞癌移植瘤耐药性的影响%The combination of recombinant rAd-p53 and adriamycin for management of primary drug resistance in chemotherapy of lung squamous cell cancer

    Institute of Scientific and Technical Information of China (English)

    都昌胡; 吴壮; 徐军

    2006-01-01

    目的 探讨野生型p53基因联合阿霉素对肺癌化疗药物敏感性的影响及导入外源性野生型p53基因对肺癌原发性耐药的影响.方法 以携带野生型P53基因的复制缺陷型腺病毒(pAd-P53)感染荷瘤肺鳞癌裸鼠动物模型.分层随机法将鼠分为4组(每组6只):单纯Ad-p53、单纯阿霉素(ADM)、Ad-p53加阿霉素组(联合组)及对照组,对照组注射同等剂量生理盐水.绘制肿瘤体积增长曲线,计算抑瘤率,观察肿瘤病理组织学变化.结果 联合组对裸鼠肿瘤重量增长抑制率为82.32%,对肿瘤体积增长抑制率为99.5%;而单独p53组对肿瘤重量增长抑制率/肿瘤体积增长抑制率分别为60.11%和85.4%;单独阿霉素组对肿瘤重量增长抑制率/肿瘤体积增长抑制率为35.4%和73.9%;对照组的肿瘤体积呈持续增长趋势.结论 野生型p53基因结合化疗药物对于提高抗肺癌药物的敏感性、克服原发耐药可能有一定的临床应用前景.

  3. In vitro Study on the Anti-tumor Activity of Hydroxyapatite Nano-particles Loaded in Adriamycin%羟基磷灰石纳米粒子负载阿霉素的体外抗肿瘤活性研究

    Institute of Scientific and Technical Information of China (English)

    刘静霆; 韩颖超; 李世普; 马雄华

    2008-01-01

    探讨羟基磷灰石(HAP)纳米粒子负载阿霉素后的体外抗肿瘤活性.通过纳米粒子与人肝癌Bel-7402细胞和人正常肝细胞L-02的体外培养,研究阿霉素负载HAP纳米粒子的心肌毒性,以及对肿瘤细胞凋亡的影响.MTT(四甲基偶氮唑蓝盐)法检测表明,阿霉素负载HAP纳米粒子对Bel-7402细胞的抑制率为95.22%,明显高于HAP纳米粒子(16.26%)和阿霉素(83.36%)(P<0.05).倒置相差显微镜观察显示,阿霉素负载HAP纳米粒子比单用阿霉素有更大的肿瘤抑制效应,并降低心肌毒性.

  4. 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.

  5. Protein expression of tubulointerstitial fibrosis mediaters in adriamycin - induced nephropathy in rats and the effect of moxonidine%大鼠阿霉素肾病肾间质纤维化介导因子表达及莫索尼定的影响

    Institute of Scientific and Technical Information of China (English)

    解汝娟; 邹春波; 穆素红; 王明奡

    2006-01-01

    目的探讨大鼠阿霉素肾病(ADR)肾组织转化生长因子β1(TGF-β1)、血小板源性生长因子-BB(PDGF-BB)、结缔组织生长因子(CTGF)的表达与肾间质纤维化的关系及莫索尼定对其影响.方法2004年8月至2004年11月选取哈尔滨医科大学动物实验中心的60只雄性健康Wistar大鼠随机分为健康对照组、模型组及莫索尼定(MOX)治疗组,两次阿霉素尾静脉注射建立模型,治疗组给予MOX 1.5 mg/(kg·d);分别于4、8、12周末留取标本,测定24 h蛋白尿、血生化、肾组织分别进行透射电镜及HE、Masson染色,应用免疫组织化学方法检测肾组织中的TGF-β1、PDGF-BB、CTGF蛋白的表达.结果血压、生化指标在治疗组和模型组差异无显著性,模型组24 h尿蛋白排泄率高于对照组,差异有显著性(P<0.05),治疗组24 h蛋白尿明显低于模型组,差异有显著性(P<0.05),与对照组比较模型组肾小管、肾间质呈明显病理改变,差异有显著性(P<0.05),治疗组损伤较模型组减轻,差异有显著性(P<0.05).PDGF-BB蛋白表达于第4周,TGF-β1、CTGF蛋白表达第8周开始明显上调,与肾间质纤维化程度呈正相关,莫索尼定治疗组上述生长因子表达下调,差异均有显著性(P<0.05).结论在大鼠阿霉素肾病肾组织中,肾间质纤维化与TGF-β1、PDGF-BB、CTGF蛋白高表达有关,莫索尼定通过下调促纤维化因子的表达,从而发挥其延缓肾纤维化及肾小球硬化作用.

  6. A comparison study between moxonidine and monopril effects on the expression of TNF-α in adriamycin induced nephropathy rats%莫索尼定及福辛普利钠对阿霉素肾病肾组织TNF-α影响的对比研究

    Institute of Scientific and Technical Information of China (English)

    邹春波; 杜玄一; 解汝娟; 穆素红; 贾西贝; 李丽

    2006-01-01

    目的 探讨肿瘤坏死因子-α(TNF-α)及血小板源性生长因子-BB(PDGF-BB)在大鼠阿霉素肾病发病中的可能作用及对比研究莫索尼定及福辛普利钠对其影响.方法 采用二次给药法尾静脉注射0.2%的盐酸阿霉素诱导肾病模型,随机等分3组(10只/组):治疗组给予莫索尼定1.5mg/(Kg·d)或福辛普利钠10mg/(Kg·d),肾病组给等量不含药物的食物丸;10只大鼠尾静脉注射等量生理盐水做为对照组.12周测血压、尿蛋白、血去甲肾上腺素(NE)、血管紧张素Ⅱ(Ang Ⅱ)、TNF-α水平,肾组织行脏、Masson染色及电镜观察,免疫组化法测定肾组织TNF-α、PDGF-BB蛋白表达.结果 肾病组24h蛋白尿、血生化指标、肾组织损伤形态学指标及TNF-α和PDGF-BB蛋白表达明显高于对照组(P<0.01),两治疗组上述损伤指标轻于肾病组(P<0.01).结论 TNF-α及PDGF-BB在ADR肾组织内高表达,可能参与肾组织损伤,莫索尼定及福辛普利钠可能通过下调TNF-α及PDGF-B蛋白表达而起肾保护作用.

  7. IL-1Ra对阿霉素肾病大鼠血清IL-6、IL-10、IL-13、IL-1的影响%EFFECTS OF IL-1 RECEPTOR ANTAGONIST ON SERUM IL-6,IL-10,IL-13,AND IL-1 LEVELS IN ADRIAMYCIN NEPHROSIS IN RATS

    Institute of Scientific and Technical Information of China (English)

    林娜; 刘运广; 覃志坚; 李强

    2009-01-01

    目的:探讨IL-1Ra对阿霉素肾病大鼠血清IL-6、IL-10、IL-13 、IL-1的影响.方法:将大鼠随机分为正常对照组(A组, n=10)、阿霉素肾病组(B组,n=10)、阿霉素肾病IL-1Ra治疗组(C组,n=10)、阿霉素肾病生理盐水治疗组(D组,n=10), 2周后检测尿24 hUP、血清IL-6、IL-10、IL-13、IL-1、Al、T-ch、BUN、Scr.结果:B、C、D组血清IL-6、IL-10、IL-13水平明显高于A组(P0.05).结论:IL-1Ra对阿霉素肾病大鼠有明显治疗作用的同时能提高抗炎细胞因子IL-6、IL-10、IL-13的血清水平.

  8. Known and Probable Human Carcinogens

    Science.gov (United States)

    ... other does not necessarily mean there is a controversy, as one agency may not have evaluated it. ... to humans Acrylamide Adriamycin (doxorubicin) Androgenic (anabolic) steroids Art glass, glass containers, and press ware (manufacture of) ...

  9. The Effects of Low to Moderate Intensity Aerobic Exercise on Fatigue in Breast Cancer Patients Following Clinical Treatment

    Science.gov (United States)

    2006-09-01

    receptor, AC, Adriamycin, Cytoxan, CMF, Cytoxan, Methotrexate, 5FU , TAM, Tamoxifen, AI, Aromatase Inhibitor, PMH, past medical history, HTN...Methotrexate, 5FU , TAM, Tamoxifen, AI, Aromatase Inhibitor, PMH, past medical history, HTN, hypertension, DM, diabetes mellitus, SLE, lupus, COPD

  10. What Happens After Treatment for Hodgkin Disease?

    Science.gov (United States)

    ... doxorubicin (Adriamycin) and mitoxantrone can also cause heart damage. Your doctor might want to check your heart function several years after your treatment. Radiation to the neck increases the chance of stroke because it can damage the blood vessels in ...

  11. Interaction of Ionizing Radiation, Genetically Active Chemicals, and Radiofrequency Radiation in Human and Rodent Cells

    Science.gov (United States)

    1990-12-01

    Martin L. Meltz, Ph.D. Patricia K. Holahan , Ph.D. Steven T. Smith, Ph.D. James J. Kerbacher, Ph.D. Victor Ciaravino, Ph.D. Department of Radiology PO...Chemicals, and Radiofrequency Radiation in Human and Rodent Cells 12 PERSONAL AUTHOR(S) Meltz. Martin L.; Holahan Patricia K.; Smith Steven Kerbacher...Potentiation of SCE Induction and Cell Killing by Adriamycin in CHO Cells (Ciaravino and Holahan , in preparation), showed that Adriamycin exposure at 410C

  12. AMPK induces vascular smooth muscle cell senescence via LKB1 dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Jin Young; Woo, Chang-Hoon [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Kang, Young Jin; Lee, Kwang Youn [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

    2011-09-16

    Highlights: {yields} An aging model was established by stimulating VSMC with adriamycin. {yields} Adriamycin increased p-LKB1, p-AMPK, p53 and p21 expressions. {yields} Inhibition of AMPK diminished SA-{beta}-gal staining and restored VSMC proliferation. {yields} p53 and p21 siRNA attenuated adriamycin-induced SA-{beta}-gal staining in VSMC. {yields} p53-p21 pathway is a mediator of LKB1/AMPK induced VSMC senescence. -- Abstract: Vascular cells have a limited lifespan with limited cell proliferation and undergo cellular senescence. The functional changes associated with cellular senescence are thought to contribute to age-related vascular disorders. AMP-activated protein kinase (AMPK) has been discussed in terms of beneficial or harmful effects for aging-related diseases. However, the detailed functional mechanisms of AMPK are largely unclear. An aging model was established by stimulating vascular smooth muscle cell (VSMC) with adriamycin. Adriamycin progressively increased the mRNA and protein expressions of AMPK. The phosphorylation levels of LKB1 and acetyl-CoA carboxylase (ACC), the upstream and downstream of AMPK, were dramatically increased by adriamycin stimulation. The expressions of p53 and p21, which contribute to vascular senescence, were also increased. Inhibition of AMPK diminished senescence-associated {beta}-galactosidase (SA-{beta}-gal) staining, and restored VSMC proliferation. Cytosolic translocation of LKB1 by adriamycin could be a mechanism for AMPK activation in senescence. Furthermore, p53 siRNA and p21 siRNA transfection attenuated adriamycin-induced SA-{beta}-gal staining. These results suggest that LKB1 dependent AMPK activation elicits VSMC senescence and p53-p21 pathway is a mediator of LKB1/AMPK-induced senescence.

  13. The inhibitory effect of pseudolaric acid B on gastric cancer and multidrug resistance via Cox-2/PKC-α/P-gp pathway.

    Directory of Open Access Journals (Sweden)

    Qian Sun

    Full Text Available AIM: To investigate the inhibitory effect of pseudolaric acid B on subcutaneous xenografts of human gastric adenocarcinoma and the underlying molecular mechanisms involved in its multidrug resistance. METHODS: Human gastric adenocarcinoma SGC7901 cells and drug-resistant SGC7901/ADR cells were injected into nude mice to establish a subcutaneous xenograft model. The effects of pseudolaric acid B with or without adriamycin treatment were compared by determining the tumor size and weight. Cyclo-oxygenase-2, protein kinaseC-α and P-glycoprotein expression levels were determined by immunohistochemistry and western blot. RESULTS: Pseudolaric acid B significantly suppressed the tumor growth induced by SGC7901 cells and SGC7901/ADR cells. The combination of pseudolaric acid B and the traditional chemotherapy drug adriamycin exhibited more potent inhibitory effects on the growth of gastric cancer in vivo than treatment with either pseudolaric acid B or adriamycin alone. Protein expression levels of cyclo-oxygenase-2, protein kinaseC-α and P-glycoprotein were inhibited by pseudolaric acid B alone or in combination with adriamycin in SGC7901/ADR cell xenografts. CONCLUSION: Pseudolaric acid B has a significant inhibitory effect and an additive inhibitory effect in combination with adriamycin on the growth of gastric cancer in vivo, which reverses the multidrug resistance of gastric neoplasm to chemotherapy drugs by downregulating the Cox-2/PKC-α/P-gp/mdr1 signaling pathway.

  14. Antitumor efficacy of poly(dimer acid-dodecanedioic acid) copolymer in mice bearing Sarcoma-180 tumor.

    Science.gov (United States)

    Guo, Wen-Xun; Shi, Zongli; Zeng, Fan-Bing; Liang, Kui; Chen, Xian-Hong; Ai, Yong-Ping; Fang, Min; Sun, Xiao; Zhang, Zhi; Hu, Li-Xin

    2007-08-01

    The drug release profiles of poly(dimer acid-dodecanedioic acid) P(DA-DDDA) copolymer containing 5% adriamycin hydrochloride (ADM) in vitro were evaluated. The biocompatibility of P(DA-DDDA) under mice skin was also evaluated, macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(DA-DDDA) copolymers containing 5% adriamycin hydrochloride (ADM) implanted subcutaneously in mice bearing Sarcoma-180 tumor exhibited increased volume doubling time (VDT) (31 +/- 1.5 days) compared to plain subcutaneous injection of ADM (7 +/- 0.9 days). The studies suggest that P(DA-DDDA) copolymer as an effective carrier for antineoplastic drug like adriamycin hydrochloride has a very good prospect in the treatment of noumenon tumors.

  15. WAVE3 is a Biomarker for Breast Cancer Progression and Metastasis

    Science.gov (United States)

    2013-01-01

    Zolendrote (Zometa) 1 12.5 Zometa-Lapitinib 1 12.5 ChemoType Doxorubicin (Adriamycin, Adriamycin-TM) 1 0.8 AC 3 2.3 AC-Docetaxel- Herceptin 1...0.8 AC- Herceptin 1 0.8 AC-Paclitaxel 7 5.5 AC-Paclitaxel-Bevacizumab (Avastin) 1 0.8 AC-Paclitaxel- Herceptin 7 5.5 AC-Taxol- Herceptin 1 0.8...Taxotere)- Clodrote 1 0.8 Cyclophosphamide(Cytoxan)/Docetaxel(Taxotere)- Herceptin 2 1.6 Docetaxel (Taxotere)-Carboplatin 1 0.8 Docetaxel

  16. [Combination chemotherapy of experimental leukemia].

    Science.gov (United States)

    Emanuel', N M; Konovalova, N P; D'iachkovskaia, R F

    1977-01-01

    In the present work an attempt was made to gain greater therapeutic effect of diazane coupled with adriamycin and sarcolysin. Leucemias L-1210 and La served as a model. In leucosis La diazane was injected once in 5 days. Either an additional injection of adriamycin two days prior to diazane injection or sarcolysin injected simultaneously with diazane enabled the authors to obtain a distinct synergestic effect. In leucemia L-1210 a simultaneous administration of diazane and sarcolysin also contributes to considerably longer survival of leucemic animals. Such combinations are likely to be promising in their clinical use.

  17. Congenital sacrococcygeal PNET and chemotherapy

    Directory of Open Access Journals (Sweden)

    Colin Patrick Hawkes

    2012-01-01

    Full Text Available We present the case of a congenital localised sacrococcygeal primitive neuroectodermal tumor treated aggressively with surgical resection and modified age-appropriate adjuvant chemotherapy. The conventional combination chemotherapy of vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide was modified to a regimen including vincristine, adriamicin, cyclophosphamide and actinomycin in order to minimise the predicted toxicity in this age group. Adjuvant "induction" chemotherapy commenced at 4 weeks of age and consisted of four cycles of vincristine, adriamycin and cyclophosphamide at 50%, 75%, 75% and 100% of recommended doses (vincristine 0.05 mg/kg, adriamycin 0.83 mg/kg daily × 2, cyclophosphamide 40 mg/kg at 3-weekly intervals. This was followed by four cycles of "maintenance" chemotherapy with vincristine (0.025 mg/kg, actinomycin (0.025 mg/kg and cyclophosphamide (36 mg/kg at full recommended doses. Cardioxane at a dose of 16.6 mg/kg was infused immediately prior to the adriamycin. Our patient is thriving at 19 months out from end of treatment.

  18. 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.

  19. Sildenafil and Phosphodiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumor Cells to Doxorubicin

    Science.gov (United States)

    2010-07-01

    promotes nor ame- liorates Adriamycin-induced cytotoxicity against either bone marrow cells or macrophages. Serafini et al. found that sildenafil reversed...Immunol 108(5):671–680 29. Serafini P et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived

  20. 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...

  1. 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.

  2. 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.

  3. Albumin-heparin microspheres as carriers for cytostatic agents

    NARCIS (Netherlands)

    Cremers, H.F.M.; Feijen, J.; Kwon, G.; Bae, Y.H.; Kim, S.W.; Noteborn, H.P.J.M.; McVie, J.G.

    1990-01-01

    Much work has been done on adriamycin-loaded albumin microspheres (Alb-MS) for chemoembolization [1–4], the rationale being that site-specific drug delivery may increase the therapeutic efficacy of the drug. Alb-Ms are being investigated because of their biocompatibility and because the degradation

  4. 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

  5. Interstitial nephritis and interstitial nephropathy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010365 Effect of fibrocytes on the progressive renal fibrosis induced by adriamycin.WANG Xian(王显),et al.Dept Nephrol, 1st Affil Hosp, Anhui Med Univ, Hefei 230022.Chin J Nephrol 2010;26(4):279-283. Objective To investigate, the effect of fibrocytes and chemokine receptor 7

  6. Thermotherapy enhanced sensitivity of multiple myeloma cell line ARH-77 to chemotherapy in vitro%热化疗对ARH-77细胞体外增敏作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    赵文飞; 魏红梅; 于华; 马晓燕; 赵文文; 霍云华; 陆月香; 张克勤

    2015-01-01

    Objective:To observe the effect of thermotherapy on the intracellular adriamycin concentration and apoptosis of ARH-77 cells in vitro. Methods:The working concentration of adriamycin against ARH-77 was determined by MTT as-say. ARH-77 cells were subjected to thermotherapy( at 40℃,41℃,42℃)and chemotherapy with adriamycin alone or in conjunction,and the cell survival rates were determined at 48h after the treatment. The cell growth inhibition effect of the treatment was evaluated with MTT assay,and the apoptosis rates of ARH-77 and alteration of intracellular adriamycin con-centration were determined by flow cytometric analyses. Results:The IC50 of adriamycin was defined as the working con-centration in the experiment. The thermotherapy at 40,41 and 42℃ for 60 min in conjunction with chemotherapy signifi-cantly inhibited the growth of ARH-77 cells(P﹤0. 01). The results of flow cytometric analyses showed that thermotherapy and adriamycin chemotherapy,used either alone or in conjunction,obviously increased the apoptosis rates of ARH-77 cells ( P﹤0. 01)and thermotherapy remarkably increased the intracellular concentration of adriamycin. Conclusion:Adriamycin chemotherapy combined thermotherapy for 60min can increase the intracellular concentration of adriamycin and the apopto-sis rates of ARH-77 cells.%目的:观察热疗联合阿霉素对人多发性骨髓瘤细胞株ARH-77细胞内的药物浓度变化及凋亡的影响。方法 MTT法确定阿霉素的工作浓度,以该浓度进行化疗或与热疗的联合,选择温度40℃、41℃及42℃,体外作用于ARH-77细胞。作用前及48 h采用台盼蓝拒染法检测肿瘤细胞的存活率;MTT法检测肿瘤细胞增殖的抑制作用;流式细胞仪检测肿瘤细胞的凋亡及细胞内药物浓度的变化。观察热疗联合阿霉素的抗肿瘤效果。结果作用48h IC50的药物浓度作为实验的工作浓度。热化疗组对ARH-77细胞有明显的抑制作用( P﹤0.01),

  7. 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.

  8. Role of radiation therapy in the treatment of pediatric non-Hodgkin's lymphomas. [Complications of local irradiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Carabell, S.C.; Cassady, J.R.; Weinstein, H.J.; Jaff, N.

    1978-11-01

    Between 1971 and 1976, 64 patients less than 18 years of age with non-Hodgkin's lymphoma were treated at Boston's Children's Hospital Medical Center-Joint Center for Radiation Therapy. A multimodality approach was used, consisting of radiation therapy (3500 to 4500 rad), surgery, and chemotherapy. Since 1973, all patients have received a regimen initially comprising Adriamycin, Prednisone, 6-Mercaptopurine, Vincristine, and L-Asparaginase. Methotrexate was substituted for Adriamycin following a cumulative total dose of 450 mg/m/sup 2/. The 5-year actuarial survival for all patients was 61%, while relapse-free survival was 54%. The actuarial and relapse-free survival for patients presenting with localized disease was 75% and 72%, respectively. Median follow-up was 40 months and all relapses occurred within 24 months of initial therapy. A multidisciplinary approach, such as the current regimen, offers a good prognosis for this disease.

  9. Flow cytometric applications of tumor biology: prospects and pitfalls. [Applications in study of spontaneous dog tumors and in drug and radiation effects on cultured V79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.; Johnson, T.S.; Tokita, N.; Gillette, E.L.

    1979-01-01

    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.

  10. The activity of etoposide (VP16) in combination chemotherapy against human bladder cancer cells in vitro

    OpenAIRE

    1991-01-01

    The activity of Etoposide (VP16) in combination chemotherapy against four human transitional cell carcinoma cell lines of bladder (TCCaB) was determined by in vitro colony formation assay. Four anti-tumor agents (methotrexate: MTX, vinblastine: VBL, adriamycin: ADM, cisplatin: DDP) were used for combination chemotherapy with VP16. The ADM + VP16 combination exhibited a strong synergistic antitumor effect against the human TCCaBs compared with other combinations in this study. The combination ...

  11. Esthesioneuroblastoma with intracranial extension: A non-surgical approach.

    Science.gov (United States)

    Thomas, Sarah Boby; Balasubramaniam, Deepak; Hiran, K R; Dinesh, M; Pavithran, K

    2016-01-01

    Esthesioneuroblastoma is a rare tumor arising from the olfactory mucosa of upper respiratory tract. The primary modality of treatment has been surgery with craniofacial resection followed by post-operative radiotherapy. There are only a few reported cases of non-surgical approaches. We report a case of esthesioneuroblastoma with intracranial extension treated with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide, Etoposide protocol followed by radiation with 5 years of follow-up. This is the first reported case using this chemotherapy schedule.

  12. [Effects of xinshuaikang granule on cardiac function and atrial natriuretic polypeptide levels in rabbits with experimental congestive heart failure].

    Science.gov (United States)

    Jin, X C; Sun, J Z; Wang, X

    1996-07-01

    Xinshuaikang (XSK) granule mainly consisted of Radix Ginseng, Aconifum carmichaeli, Ligustici wallichii, Semen Lepidii seu Descurainiae, etc. Thirty-five white rabbits of Japanese strain with big ears were used and five groups were divided randomly. The models of chronic heart failure (CHF) was made by injection of adriamycin through the marginal vein of rabbit's ear. Only one group without adriamycin injection was taken as blank group. After the making of models, Xinbao (XB) was used to treat one group which was regarded as control group, XSK was used to treat two model groups, one used higher dose, the other one used lower dose. Fifteen days was taken as a course of treatment. The results were: the body weight of all model groups was heavier than that without adriamycin. After a course of treatment, the body weight of the groups treated by XSK or XB decreased rapidly, the general conditions of the three groups were improved; the two drugs could reduce heart rate and enhance heart function, at the same time they reduced the level of atrial natriuretic polypeptide (ANP) in plasma. The best results was obtained in XSK group with higher dose, the effect of XSK group with lower dose was equivalent to that of XB group. Hence, XSK granule could enhance the CHF rabbits' heart function, improve their heart endocrine activity, this drug had a reliable effect on CHF.

  13. HnRNP K contributes to drug resistance in acute myeloid leukemia through the regulation of autophagy.

    Science.gov (United States)

    Zhang, JinFang; Liu, XiaoLi; Lin, YuDeng; Li, YuLing; Pan, JianWei; Zong, Sa; Li, YongKang; Zhou, Yang

    2016-09-01

    The goal of this study was to explore the role of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in drug resistance through the regulation of autophagy in acute myeloid leukemia (AML). First, we used fluorescence quantitative polymerase chain reaction (PCR) to verify the connection between the expression level of hnRNP K and the level of drug resistance in AML. We then used Western blotting to determine the expression level of the autophagy-related proteins microtubule-associated protein light chain 3 I and II (LC3 I/II) after the modulation of hnRNP K by ribonucleic acid (RNA) interference. Finally, an analysis of adriamycin drug sensitivity was conducted before and after the modulation of hnRNP K expression. hnRNP K and LC3 I/II were significantly overexpressed in the bone marrow of nonremission patients and in drug-resistant cell lines; however, the expression of LC3 I/II was decreased when the expression of hnRNP K was reduced and drug sensitivity to adriamycin could be restored. hnRNP K may be involved in the development of adriamycin resistance in AML through the regulation of autophagy.

  14. 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.

  15. Protection effects of Nicorandil on myocardial of rats dameged by Adri-amycin%尼可地尔对阿霉素损伤大鼠心肌的保护作用

    Institute of Scientific and Technical Information of China (English)

    刘梦林; 万军; 王梦龙; 石磊; 冯颖

    2014-01-01

    Objective To investigate the protection effect of Nicorandil on myocardial of rats dameged by Adriamycin. Methods 45 male SD rats were randomly divided into control group (group A, n=15), Adriamycin group (group B, n=15) and Adriamycin combined with Nicorandil group (group C, n=15). The rats in group B and C were performed with intraperitoneal injection of Adriamycin at the dose of 2.5 mg/kg a week , those in group A were performed with in-traperitoneal injection of normal saline at the dose of 2.5 mg/kg a week, for 6 weeks. From the eighth week, rats in group C were performed with Nicorandil by stomach lavaging at the dose of 3 mg/kg once a day for 30 days. Then the rats were sacrificed after cardiac function accessed by echocardiography. Meanwhile, collagen volume fraction was mea-sured in each group by sirius red staining. Results①At the end of molding, mean weight of rats in group B was lighter than those in group A and C (P0.05). Conclusion Nicorandil has protection effects on myocardial of rats dameged by Adriamycin.%目的:探讨尼可地尔对阿霉素损伤大鼠心肌的保护作用。方法将45只雄性SD大鼠用随机数字表法分为对照组(A组,n=15)、阿霉素模型组(B组,n=15)、尼可地尔+阿霉素组(C组,n=15)。 B、C组大鼠每周经腹腔注射阿霉素2.5 mg/kg,A组大鼠每周经腹腔注射生理盐水2.5 mg/kg,共持续6周。第8周开始C组大鼠每次灌胃法灌入尼可地尔3 mg/kg,1次/d,持续30 d。之后通过心脏彩超检测三组大鼠的心脏功能并将其处死。用天狼星红染色法检测各组大鼠心肌的胶原容积分数。结果①造模结束时,B组大鼠平均体重小于A、C组(P0.05)。结论尼可地尔对阿霉素损伤心肌有保护作用。

  16. 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.

  17. Characterisation of a mouse tumour cell line with in vitro derived resistance to verapamil.

    OpenAIRE

    Twentyman, P. R.; Wright, K A; Fox, N. E.

    1990-01-01

    We have established a subline (EMT6/VRP) of the mouse tumour cell line EMT6/P with acquired resistance to the calcium transport blocker verapamil (VRP). The subline was 4-fold resistant to the cytoxicity of VRP alone compared with the parent line but of similar sensitivity to adriamycin, vincristine or colchicine. EMT6/VRP cells growing in 75 micrograms ml-1 VRP were morphologically different from and larger in diameter than EMT6/P cells, but these two parameters reverted almost to normal wit...

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

    Energy Technology Data Exchange (ETDEWEB)

    Orlowski, E.P.; Hansen, R.M.; Anderson, T.; Hanson, G.A.; Kun, L.E.; Pisciotta, A.V.

    1984-05-01

    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.

  19. 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.

  20. 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

  1. Mechanisms for Breast Cancer Cell Resistance to Doxorubicin and Solutions to Resistance and Side Effects

    Science.gov (United States)

    2001-10-01

    formaldehyde virtual crosslink 1523 pp. 1001N VVUU-LYJLVU/4P5bC 11U1t II1dLLCI "© 2000 Elsevier Science Inc . All rights reserved. PHI S0006-2952(00)00521-S... Science Inc . KEY WORDS. adriamycin; GSH conjugation; GST inhibition; multidrug resistance; MCF-7; DOX The resistance of cancer cells acquired upon exposure...with K, at 250 in the 1-2 ýLM range, scarcely dependent on their stereochemistry at C(7). BIOCHEM PHARMACOL 60;12:1915-1923, 2000. © 2000 Elsevier

  2. Effects of Quercetin and Resveratrol combined Reversing Drug Resistance of Leukemia Cell Line HL-60-ADM%槲皮素联合白藜芦醇逆转白血病细胞株HL-60-ADM耐药性的影响

    Institute of Scientific and Technical Information of China (English)

    张复华; 尹松梅; 牛国敏; 杨国雷; 凌奕文; 李蕊; 徐嘉愉

    2014-01-01

    Objective The recent study showed that querctin and resveratrol can reverse multidug resistance in leukemia. The aim of this study was to investigate the reversal multidug resistance effect by querctin and resveratrol. Methods CCK-8 assay was used to compare the toxic effect of querstin or resveratrol alone with that in combination with adriamycin on HL-60-A cells. Results Compared to HL-60 cell line, the IC50 value of adriamycin for HL-60-A increased signiifcantly, it showed that HL-60-A was multidug resistance cell line;querctin or resveratrol could inhibite cell proliferation of HL-60-A in a dose-dependent pattern, while the toxic effect of querctin combined with resveratrol was greater than that of the cells treated with querstin or resveratrol alone;the low-dose of querctin and resveratrol could enhance the sensitivity of adriamycin on HL-60-A, and querstin combined with resveratrol could further enhance the toxic effect of adriamycin. Conclusion Querctin and resveratrol both illustrated signiifcant reversal effect on the leukemia cell line, while the reversal effect of querctin was greater than resveratrol, the synergistic reversal effect of querstin combined with resveratrol was determined.%目的:研究槲皮素(Quercetin,Que)及白藜芦醇(Resveratrol,Res)单用及联用对HL-60-A细胞株耐药性的影响。方法不同浓度阿霉素(adriamycin,ADM)孵育HL-60和HL-60-A细胞48 h后CCK-8法测定细胞存活率;Que、Res单用或联用,及加用ADM 48 h测定HL-60-A细胞存活率。结果 ADM作用48 h后,HL-60-A较HL-60细胞IC50明显增高增加提示为耐药细胞株;Que及Res在12.5~150μmol/L时呈剂量依赖性杀伤HL-60-A细胞,Que毒性作用更强,二者可以进一步增强杀伤效应;Que及Res低剂量时可增强ADM对HL-60-A敏感性,二者联用进一步增强ADM的杀伤效应。结论 Que及Res均可逆转白血病细胞耐药性,Que作用较强,二者联合可更有效逆转肿瘤耐药。

  3. Improved risk assessment by screening sperm parameters.

    Science.gov (United States)

    Plassmann, S; Urwyler, H

    2001-02-28

    The question of whether a 4 or 9 week premating treatment period is more suitable in studies for effects on fertility and early embryonic development, and the extent to which the screening of sperm parameters may contribute to the detection of effects, has been under discussion since the ICH guideline changed in 1994/1995. This study presents a comparison between 4 and 9 weeks treatment with known male reproductive toxicants with regard to sperm motility, count, morphology, abnormal movements and testicular and epididymal histopathology. Mating outcome was examined after 4 weeks treatment. Three compounds with different targets and mechanisms of action were chosen: two testicular toxicants, Pyridoxine and Adriamycin and the epididymal toxicant, alpha-Chlorohydrine. Sperm motility was reduced in males treated with Pyridoxine (markedly) and alpha-Chlorohydrine (slightly) after 4 weeks treatment and in males treated with Adriamycin after 9 weeks treatment. With Pyridoxine and Adriamycin, sperm count was significantly increased after 4 weeks. Histopathological examination after 4 weeks showed characteristic changes leading to marked testicular tubular atrophy at 8/9 weeks, which was confirmed by a significantly reduced sperm count at 8/9 weeks. With alpha-Chlorohydrine, sperm count was not affected and the results of the histopathological examination were equivocal. Changes in sperm morphology were observed after 4/9 weeks of treatment with Pyridoxine. Mating outcome after 4 weeks was markedly affected with both Pyridoxine and alpha-Chlorohydrine, but no effect was observed with Adriamycin. The results of this study indicate that the two testicular toxicants would have been detected as male reproductive toxicants in a 4-week general toxicity study with routine testicular histopathology and examination of sperm parameters, without the need for mating trials. For the epididymal toxicant, alpha-Chlorohydrine, there was slightly reduced sperm motility after 4 weeks

  4. Specific activities of poetam preparation (superlow-doses of antibodies to erythropoietin) and recombinant erythropoietin.

    Science.gov (United States)

    Dygai, A M; Zhdanov, V V; Udut, E V; Simanina, E V; Gur'yantseva, L A; Khrichkova, T Yu; Epshtein, O I; Sergeeva, S A

    2006-09-01

    We compared the capacity of superlow-dose of antibodies to erythropoietin (Poetam) and recombinant erythropoietin (Recormon) to stimulate the recovery of adriamycin-suppressed erythropoiesis in mice. Both preparations exhibited high erythron activation capacity and considerably increased the content of erythrocytes and reticulocytes in the peripheral blood and content of erythrokaryocytes and erythroid precursors in the hemopoietic tissue of experimental animals. The effect of Recormon manifested immediately after injection, while the effect of Poetam was somewhat delayed, but more lasting (due to activation of host erythropoietin system).

  5. Lymphatic system and lymphoma

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930583 Analysis of therapeutic efficacy of com- bination chemotherapy and adjuvant radiothera-py in 207 cases of diffuse non—Hodgkin’s lym-phoma.YONG Weiben(勇威本),et al.BeijingCancer Res Instit,Beijing,100000. Chin J Hema-tol 1992;13(12):638—640.Two hundred and seven cases of diffuse non—Hodgkin’s lymphoma(D—NHL)were treatedwith combination chemotherapy(cyclophospha-mide,vincristine,procarbazine,prednisone andpingyingmycin or adriamycin)and adjuvant ra-diotherapy.Complete remission(CR)wasachieved in 94 of 207 patients(45.4%),partial

  6. Effect of carvedilol on oxidative stress in rabbits With driamycin cardiomyopathy%卡维地洛对阿霉素心肌病兔氧化应激的影响

    Institute of Scientific and Technical Information of China (English)

    贺莉; 肖建明; 付晖; 肖幸; 肖志超; 张存泰; 顾晔; 马业新

    2012-01-01

    目的:研究卡维地洛对阿霉素心肌病兔氧化应激的影响,并探讨氧化应激与慢性心肌毒性之间的关系.方法:将40只日本长耳白兔随机分为对照组、阿霉素组、美托洛尔组和卡维地洛组,每组各10只.耳缘静脉注射阿霉素(每次1 ml·kg-1,每周2次,共8周)建立阿霉素心肌病模型,对照组采用耳缘静脉注射0.9%氯化钠(每次1 ml·kg-1,每周2次,共8周).3周后,对照组和阿霉素组以0.9%氯化钠(5 ml·kg-1·d-1)灌胃,美托洛尔组和卡维地洛组分别给予美托洛尔(5 mg· kg-1·d-1)和卡维地洛(5 mg· kg-1·d-1)灌胃.2个月后,超声心动图观察各组心脏结构变化,检测兔血清中丙二醛(MDA)、超氧化物岐化酶(SOD)和N末端前体脑钠肽(NT-proBNP)水平,并制备兔左室楔形心肌块的灌注模型,记录快频率程序刺激条件下室性心律失常的发生率.结果:与对照组比较,阿霉素组左室舒张末径(LVEDd)增大、左室射血分数(LVEF)降低(均P<0.05),血清SOD活性降低、NT-proBNP和MDA浓度升高,室性心律失常发生率增加(均P<0.05).与阿霉素组比较,美托洛尔组无显著性变化,卡维地洛组LVEDd缩小、LVEF升高(均P<0.05),血清SOD活性增加、NT-proBNP和MDA浓度降低,室性心律失常发生率明显降低(均P<0.05).结论:与美托洛尔比较,卡维地洛对阿霉素心肌病有保护作用,并能降低室性心律失常的发生,其机制与氧化自由基降低密切相关.%Objective:To investigate the effect of carvedilol on oxidative stress in rabbits with adriamycin cardiomyopathy and the relationship between oxidative stress and adriamycin cardiomyopathy. Method: Forty Japanese white rabbits were randomly divided into four groups (n=10 each): control group, adriamycin group, metoprolol group and carvedilol group. Rabbits in the adriamycjn group, metoprolol group and carvedilol group were intravenously injected through auri-edge with adriamycin.hydrochloride (1 ml · kg

  7. Malignant phyllodes tumor with chondro and osteosarcomatous differentiation and secondaries in lungs

    Directory of Open Access Journals (Sweden)

    Satya Narayan

    2014-01-01

    Full Text Available Phyllodes tumor is a rare breast tumor, with neoplastic epithelial and stromal components for 10 cm in size and firm in consistency. She underwent left mastectomy. The histopathology revealed a malignant phyllodes tumor with sarcomatous stromal overgrowth and heterogeneous chondro and osteosarcomatous differentiation. At 2 months after surgery, she reported to us with secondaries in bilateral lungs. We planned palliative chemotherapy in view of good general condition of the patient and lung metastasis. Chemotherapy included ifosfamide, adriamycin and cisplatin as per standard regimen every 3 weekly. After three cycles, her lung metastasis cleared completely. It was planned to continue same chemotherapy for six cycles.

  8. Primary synovial sarcoma of pericardium:A case report%心包原发性滑膜肉瘤1例报道

    Institute of Scientific and Technical Information of China (English)

    Rangreze Imran; Banday Manzoor Ahmad; Sheikh Aejaz Aziz; Bhat Salma; Mohammad Latif Charoo

    2011-01-01

    Primary pericardial sarcomas are extremely rare. We report a case of 19 year old male who presented with cough,dyspnoea, and orthopnea. Investigations and exploratory thoracotomy revealed a large pericardial mass. Surgical debulking of the tumor was performed and the histopathological examination was compatible with synovial sarcoma. The tumor was unresectable due to its invasion and adhesion to mediastinal structures. Hence patient was started on palliative chemotherapy (adriamycin and ifosfamide based). Patient showed an initial symptomatic response but later on there was a clinical progression and died within six months of his diagnosis.

  9. Effect of compound huangjing oral liquid on myocardial myosin heavy-chain in rats with heart failure%复方黄精口服液对心力衰竭大鼠心肌肌球蛋白重链变化的作用

    Institute of Scientific and Technical Information of China (English)

    陈金水; 吴天敏; 林圣远; 杜建; 吴可贵; 王华军; 陈小明

    2005-01-01

    均有不同程度下降(P<0.01或P<0.05),以上变化以中剂量组作用最佳.结论:复方黄精口服液能减轻阿霉素致心力衰竭的毒性反应,其机制与复方黄精口服液可提高心肌α-肌球蛋白重链的转化有关,且呈剂量依赖性.%BACKGROUND: Adriamycin is anthracycline-based drugs of anti-cancer and inhibits many malignant tumors. But due to the large toxicity, it will induce dose-dependent cardiac toxicity, resulting in heart failure in severe case. Compound huangjing oral lipid is against the injury of free radial and is expected to be applied as an assistant therapy for heart failure.OBJECTIVE: To probe into the therapeutic effect of compound huangjing oral lipid and its mechanism on heart failure.DESIGN: Randomized controlled observation was designed.SETTING: Department of Traditional Chinese Medicine , First Affiliated Hospital of Fujian University of Medical Science, Fujian College of Traditional Chinese Medicine.MATERIALS: The experiment was performed in Fujian Research Institute of Hypertension from August 2000 to May 2001, in which, 66 rats were employed and randomized into 6 groups, 11 rats in each one.METHODS: In normal group, physiological saline of equal volume was injected abdominally. In adriamycin group, adriamycin 1mg/kg was injected abdominally on the 2nd and 4th days after experiment, 2 mg/kg was injected on the 6th and 8th days, 3 mg/kg was on the 10th and 12th days and 4 mg/kg was on the 14th and 16th days. The dose was accumulated up to 20 mg/kg in 16 days. In adriamycin+compound huangjing oral liquid 2 mL (small-dose group), adriamycin +compound huangjing oral liquid 4 mL (moderate-dose group) and adriamycin+compound huangjing oral liquid 6ml (large-dose group), the oral lipid of various doses was applied for gastric perfusion everyday successively from the beginning of experiment, in which, the dose of adriamycin was same as adriamycin group. In adriamycin+tebonin group (tebonin group), tebonin 450 mg/kg was administrated once

  10. Experimental studies of some moderately fast processes initiated by radiation

    Science.gov (United States)

    Butler, J.; Hodgson, B. W.; M. Hoey, Brigid; Land, E. J.; Lea, J. S.; Lindley, Elizabeth J.; Rushton, F. A. P.; Swallow, A. J.

    Numerous improvements have been made to the Paterson Institute linear accelerator since its installation in 1967. New light sources, improved light guidance, smaller cells and a wider range of photo-detecting devices are now in routine use. Data are collected and processed by a computer-based method which has replaced the original oscilloscope-based system. Processes taking place over more than a few seconds can be studied with an arrangement combining pulse radiolysis with an ordinary spectrophotometer and arrangements for "single-shot" studies of faster processes are now being designed. Detection methods are also available which do not rely on transmission of light, and transient changes in conductivity can be measured. Among the systems which have been extensively studied are the Fricke dosimeter, in which measured overall yields can now be quantitatively correlated with the rate constants of 34 individual reactions taking place. Studies have also been conducted with peptides and proteins in which electrochemically-driven charge transfers have been demonstrated between methionine, tryptophan, tyrosine and cysteine/cystine units. Free radical reactions in Mitomycin C have been elucidated which are consistent with pulse radiolysis observations and the formation of radiolytic products as determined by HPLC. Adriamycin reduction has also been studied: the Adriamycin semiquinone is unusually stable with respect to dismutation but its lifetime is limited by a decomposition process in which daunosamine is expelled. The expulsion is followed by a further rearrangement. Many of the reactions investigated require tens or hundreds of seconds to reach essential completion.

  11. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  12. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

    Directory of Open Access Journals (Sweden)

    Candelaria Myrna

    2006-01-01

    Full Text Available Abstract Background Among the epigenetic alterations occurring in cancer, DNA hypermethylation and histone hypoacetylation are the focus of intense research because their pharmacological inhibition has shown to produce antineoplastic activity in a variety of experimental models. The objective of this study was to evaluate the combined antineoplastic effect of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in a panel of cancer cell lines. Results Hydralazine showed no growth inhibitory effect on cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when used alone. On the contrary, valproic acid showed a strong growth inhibitory effect that is potentiated by hydralazine in some cell lines. Individually, hydralazine and valproic acid displayed distinctive effects upon global gene over-expression but the number of genes over-expressed increased when cells were treated with the combination. Treatment of HeLa cells with hydralazine and valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin and adriamycin. A higher antitumor effect of adriamycin was observed in mice xenografted with human fibrosarcoma cells when the animals were co-treated with hydralazine and valproic acid. Conclusion Hydralazine and valproic acid, two widely used drugs for cardiovascular and neurological conditions respectively have promising antineoplastic effects when used concurrently and may increase the antitumor efficacy of current cytotoxic agents.

  13. Levistolide A overcomes P-glycoprotein-mediated drug resistance in human breast carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Fei CHEN; Tao WANG; Jia WANG; Zi-qiang WANG; Ming QIAN

    2008-01-01

    Aim:The aim of the present study was to investigate the reversing effect of levistolide A (LA) on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in human breast carcinoma Bcap37/MDR1 cells. Methods:After chemotherapeu-tic drugs (adriamycin or vincristine) used alone or in combination with LA, cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazo-lium bromide assay and cell cycle distribution by flow cytometry. RT-PCR was used to detect MDR1 gene transcription and the Western blot assay was used to assess P-gp expression and the cleavages of poly(ADP-ribose) polymerase and caspase-3. Apoptosis was detected by terminal transferase-mediated dUTP nick end-labeling assay. Moreover, the P-gp function was evaluated by the intracellu-lar accumulation of the P-gp substrate detected by flow cytometry. Results:We found the subcytotoxic doses of LA significantly enhanced adriamycin- or vinc-ristine-induced G2/M arrest and apoptosis. These effects were consistent with the ability of LA to inhibit P-gp function. Moreover, LA dramatically enhanced the verapamil (VER) ability to reverse drug resistance. Conclusion:LA has the poten-tial to be developed as a novel P-gp modulator. Furthermore, the combination of LA and VER might represent a more sufficient but less toxic anti-MDR regimen.

  14. Sonic Hedgehog, VACTERL, and Fanconi anemia: Pathogenetic connections and therapeutic implications.

    Science.gov (United States)

    Lubinsky, Mark

    2015-11-01

    Three systems with VACTERL association findings- mutations of the Sonic Hedgehog (SHH) signaling pathway in mice, murine adriamycin teratogenicity, and human Fanconi anemia (FA) pathway mutations, may all involve a similar mechanism. SHH is up-regulated in irradiated cells, and DNA breaks common with radiation damage in the adriamycin and FA systems are plausible signals for such effects, which would affect development. Since FA related DNA breakage occurs throughout life, SHH disturbances may account for later FA related findings involving hematopoietic and malignancy issues. In support, androgen, a standard treatment for FA hematologic failure, down-regulates SHH, and common FA malignancies such as squamous cell carcinomas and acute myeloid leukemia have been linked to enhanced SHH function. This suggests that interventions lowering SHH levels may be useful therapeutically. Also supporting a connection between pre- and post- natal findings, the frequency and number of VACTERL anomalies with FA correlate with the severity and onset of hematopoietic and malignancy issues. In FA, radial anomalies are the most common of these defects, followed by renal findings, while vertebral and gastrointestinal anomalies are relatively uncommon, a pattern that differs from observations of the VACTERL association. Genes with more severe effects also show a greatly increased incidence of brain abnormalities, and a paucity of such findings with other FA genes suggests that brain development is relatively refractory to SHH related effects, accounting for the rarity of such findings with the association.

  15. An ultrasensitive electrochemical DNA biosensor based on a copper oxide nanowires/single-walled carbon nanotubes nanocomposite

    Science.gov (United States)

    Chen, Mei; Hou, Changjun; Huo, Danqun; Yang, Mei; Fa, Huanbao

    2016-02-01

    Here, we developed a novel and sensitive electrochemical biosensor to detect specific-sequence target DNA. The biosensor was based on a hybrid nanocomposite consisting of copper oxide nanowires (CuO NWs) and carboxyl-functionalized single-walled carbon nanotubes (SWCNTs-COOH). The resulting CuO NWs/SWCNTs layers exhibited a good differential pulse voltammetry (DPV) current response for the target DNA sequences, which we attributed to the properties of CuO NWs and SWCNTs. CuO NWs and SWCNTs hybrid composites with highly conductive and biocompatible nanostructure were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and cyclic voltammetry (CV). Immobilization of the probe DNA on the electrode surface was largely improved due to the unique synergetic effect of CuO NWs and SWCNTs. DPV was applied to monitor the DNA hybridization event, using adriamycin as an electrochemical indicator. Under optimal conditions, the peak currents of adriamycin were linear with the logarithm of target DNA concentrations (ranging from 1.0 × 10-14 to 1.0 × 10-8 M), with a detection limit of 3.5 × 10-15 M (signal/noise ratio of 3). The biosensor also showed high selectivity to single-base mismatched target DNA. Compared with other electrochemical DNA biosensors, we showed that the proposed biosensor is simple to implement, with good stability and high sensitivity.

  16. AATF/Che-1 acts as a phosphorylation-dependent molecular modulator to repress p53-driven apoptosis.

    Science.gov (United States)

    Höpker, Katja; Hagmann, Henning; Khurshid, Safiya; Chen, Shuhua; Hasskamp, Pia; Seeger-Nukpezah, Tamina; Schilberg, Katharina; Heukamp, Lukas; Lamkemeyer, Tobias; Sos, Martin L; Thomas, Roman K; Lowery, Drew; Roels, Frederik; Fischer, Matthias; Liebau, Max C; Resch, Ulrike; Kisner, Tülay; Röther, Fabian; Bartram, Malte P; Müller, Roman Ulrich; Fabretti, Francesca; Kurschat, Peter; Schumacher, Björn; Gaestel, Matthias; Medema, René H; Yaffe, Michael B; Schermer, Bernhard; Reinhardt, H Christian; Benzing, Thomas

    2012-10-17

    Following genotoxic stress, cells activate a complex signalling network to arrest the cell cycle and initiate DNA repair or apoptosis. The tumour suppressor p53 lies at the heart of this DNA damage response. However, it remains incompletely understood, which signalling molecules dictate the choice between these different cellular outcomes. Here, we identify the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 as a critical regulator of the cellular outcome of the p53 response. Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. Phosphorylation results in the release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation where AATF binds to the PUMA, BAX and BAK promoter regions to repress p53-driven expression of these pro-apoptotic genes. In xenograft experiments, mice exhibit a dramatically enhanced response of AATF-depleted tumours following genotoxic chemotherapy with adriamycin. The exogenous expression of a phospho-mimicking AATF point mutant results in marked adriamycin resistance in vivo. Nuclear AATF enrichment appears to be selected for in p53-proficient endometrial cancers. Furthermore, focal copy number gains at the AATF locus in neuroblastoma, which is known to be almost exclusively p53-proficient, correlate with an adverse prognosis and reduced overall survival. These data identify the p38/MK2/AATF signalling module as a critical repressor of p53-driven apoptosis and commend this pathway as a target for DNA damage-sensitizing therapeutic regimens.

  17. 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.

  18. 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.

  19. 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.

  20. DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

    Science.gov (United States)

    Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

    2016-05-01

    Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

  1. Reversal Effect of Silymarin on Drug Resistant Breast CancerCell MCF-7/ADM%水飞蓟素逆转人乳腺癌耐药细胞株MCF-7/ADM耐药性实验研究

    Institute of Scientific and Technical Information of China (English)

    陆一丹; 徐良额; 裘嘉琪; 毛丹漪; 刘晓谷; 王大维

    2016-01-01

    Objective To investigate the effect of silymarin on drug resistance of breast cancer cell line MCF-7/ADM. Methods The toxicant effect of adriamycin to MCF-7/S(sensitive strain) and MCF-7/ADM(drug-resistant strain) was measured by CCK-8 in vitrofor resistant index. Silymarin was screened in advance and the dose of 10μg/ml was nontoxicant to MCF- 7/ADM, then MCF- 7/ADM was treated with this dose of silymarin (10μg/ml) to observe the reversal effect of silymarin. Results IC50 of adriamycin to MCF-7/S and MCF-7/ADM were 1.773 μg/ml and 43.812μg/ml, respectively. Drug-resistant index of MCF-7/ADM was 24.7. Silymarin increased cell toxic ef-fect of adriamycin. After treated with 10μg/mlsilymarin (inhibition rate was 2.0%) combining with adriamycin for 48h, IC50of adriamycine declined to 7.798μg/ml, and the reversal index was 5.6 (P<0.01). Conclusion Silymarin could partly reverse drug-resistance of MCF- 7/ADMto adriamycinein vitro.%目的 观察水飞蓟素(Silymarin,Sily)对人乳腺癌耐药细胞株MCF-7/ADM的逆转耐药作用.方法 以CCK-8法测定阿霉素(Adm)对人乳腺癌敏感细胞株MCF-7/S和耐药细胞株MCF-7/ADM的毒性作用,计算出耐药倍数.以无细胞毒性的Sily(10μg/mL)作为逆转耐药剂,联合Adm观察其对耐药细胞株MCF-7/ADM的逆转耐药作用,计算得逆转倍数.结果 (1)Adm对MCF-7/S和MCF-7/ADM的半数抑制浓度(IC50)分别为1.773μg/mL和43.812μg/mL,耐药倍数为24.7倍.(2) Sily能够增强ADM对MCF-7/ADM的细胞毒作用.以10μg/mL(抑制率为2.0%)的Sily联合Adm作用于MCF-7/ADM 48h后,耐药细胞株的IC50降至7.798μg/mL,逆转倍数为5.6倍(P<0.01).结论 Sily能够逆转人乳腺癌耐药细胞株MCF-7/ADM的耐药性.

  2. Biological functions of the nude mice subcutaneous tumor established by MDA-MB-468 and SK-BR-3 breast cancer cells%MDA-MB-468和SK-BR-3乳腺癌细胞建立裸鼠皮下种植瘤的生物学功能

    Institute of Scientific and Technical Information of China (English)

    赵期康; 吴颖; 莫雪丽; 熊兵红

    2015-01-01

    characteristics in to the subcutaneous transplantation tumor in nude mice.To judge the impact of biological function of adriamycin on two breast cancer cell subcutaneous implanted tumor in nude mice.Methods 80 nude mice were randomly divided into group MDA-MB-468 and group SK-BR-3,group MDA-MB-468 mice subcutaneous injection of breast cancer cells MDA-MB-468,SK-BR-3 mice by subcutaneous injection of breast cancer cell line SK-BR-3,with 40 rats in each group.Selection of half the number of mice by subcutaneous injection of the cells grown in nude mice right groin area,1 daily injections for 4 weeks after injection,mice were sacrificed and the tumor body.Two groups of nude mice tumor volume measurement,calculation of tumor volume inhibition rate,remove the other half mice in two groups in a mouse model of adriamycin,will slow preparation into two groups of mice subcutaneous tumor model by injection,daily 1 times,continuous injection for 4 weeks.Observation of two nude mice,the growth of the dietandmental status,tumor record,mice were killed after 4 weeks,the tumor volume,the tumor size was measured.The apoptosis index of tumor cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) in two groups of mice tumor tissue,to observe the effect of adriamycin on the two groups of breast cancer cell cycle and apoptosis.Results (1) Tumor growth:at eighth weeks,two groups of mice tumor volume were (3.212 ±0.151) and (2.924 ±0.316) cm3,the difference was statistically significant between the two groups (t =2.758,P < 0.05).Results the tumor volume inhibition rate.(2) After adriamycin injection:two groups of mouse model of breast cancer after injection of adriamycin,subcutaneous tumors stopped growing and gradually narrowing,4 weeks later,the tumor volume was statistically significant difference between the two groups of mice (x2 =2.14,P < 0.05),detection index of tumor cell apoptosis by TUNEL,there was statistical significance the difference between the two groups (x2 =3.59,P

  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. 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

  5. Anaplastic thyroid carcinoma: a new approach.

    Science.gov (United States)

    Simpson, W J

    1980-01-01

    Less than 10% of patients with anaplastic thyroid carcinoma survive 5 years when treated by operation and conventional irradiation, but survivors who are disease-free at 2 years appear to be cured. The administration of a small number of large radiation fractions (350 to 800 rads) failed to eradicate the local disease in 14 patients, all of whom died within 9 months. Hyperfractionation (100 rads qid at 3-hour intervals) caused complete tumour regression of 6 of 14 patients and partial regression in 7 others; the 1 patient whose tumour failed to respond was treated only once daily. However, the cost was high: two patients died of spinal cord necrosis and a third of pneumonitis due to the unexpected increase in radiation toxicity caused by the concurrent administration of Adriamycin. If an effective systemic treatment can be devised for this disease, hyperfractionation may be capable of eradicating the massive local tumour masses so characteristic of anaplastic thyroid carcinoma.

  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. Identification of Semaphorin3B as a Direct Target of p53

    Directory of Open Access Journals (Sweden)

    Kensuke Ochi

    2002-01-01

    Full Text Available A cDNA microarray analysis indicated that Semaphorin3B. (20Sema3B, a gene whose product is involved in axon guidance and axonal repulsion, is inducible by p53. Introduction of exogenous p53 into a glioblastoma cell line lacking wild-type p53. (20U373MG dramatically induced expression of Sema3B mRNA. An electrophoretic mobility shift assay and a reporter assay confirmed that a potential p53 binding site present in the promoter region had p53-dependent transcriptional activity. Expression of endogenous Sema3B was induced in response to genotoxic stresses caused by adriamycin treatment or UV irradiation in a p53-dependent manner. Ectopic expression of Sema3B in p53-defective cells reduced the number of colonies in colony formation assays. These results suggest that Sema3B might play some role in regulating cell growth as a mediator of p53 tumor- suppressor activity.

  8. Lymphocyte Rich Hodgkin's Lymphoma Presented with Warm Hemolytic Anemia: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Jorge M. Hurtado-Cordovi

    2011-01-01

    Full Text Available Hodgkin's lymphoma accounts for ten percent of all lymphomas. In the United States, there are about 8000 new cases every year. This paper describes a case of lymphocyte-rich Hodgkin's lymphoma (LRHL manifested by autoimmune hemolytic anemia (AIHA. A 27-year-old Israeli male presented with dizziness associated with one month of low-grade fevers and night sweats; he also complained of persistent cough, pruritus, and ten-pound weight lost during this time. The CBC revealed hemoglobin of 5.9 gm/dL, and direct Coomb's test detected multiple nonspecific antibodies consistent with the diagnosis of AIHA. Chest, abdomen, and pelvic CT scan showed mediastinal lymphadenopathy and splenomegaly. Lymph node biopsy revealed classic LRHL. AIHA resolved after completion of the first cycle of chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD; after six cycles, he went into complete remission. Although infrequent, AIHA can be responsible for the presenting symptoms of HL.

  9. Lathyrol diterpenes as modulators of P-glycoprotein dependent multidrug resistance: structure-activity relationship studies on Euphorbia factor L3 derivatives.

    Science.gov (United States)

    Jiao, Wei; Wan, Zhongmin; Chen, Shuang; Lu, Runhua; Chen, Xiaozhen; Fang, Dongmei; Wang, Jiufeng; Pu, Shengcai; Huang, Xin; Gao, Haixiang; Shao, Huawu

    2015-05-14

    Five series of 37 new acylate and epoxide derivatives (3-39) of Euphorbia factor L3, a lathyrol diterpene isolated from Euphorbia lathyris, were designed by modifying the hydroxyl moiety of C-3, C-5, or C-15. Chemoreversal effects of the acylates on multidrug resistance (MDR) were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein (P-gp). Eight derivatives exhibited greater chemoreversal ability than verapamil (VRP) against adriamycin (ADR) resistance. Compounds 19 and 25 exhibited 4.8 and 4.0 times, respectively, more effective reversal ability than VRP against ADR resistance. To determine the key characteristics of Euphorbia factor L3 derivatives that contribute to MDR reversal, we conducted a structure-activity relationship study of these compounds. The simulation studies indicated different possible mechanisms and revealed the important influence of hydrophobic interactions and hydrogen bonds in the flexible cavity of P-gp.

  10. Central type primitive neuroectodermal tumor/neuroblastoma of the uterus: a case report.

    Science.gov (United States)

    Shimada, Chisa; Todo, Yukiharu; Okamoto, Kazuhira; Akashi, Daisuke; Yamashiro, Katsushige; Hasegawa, Tadashi

    2014-10-01

    We encountered a 63-year-old woman who had a uterine tumor with peritoneal dissemination and para-aortic lymph node metastasis. Microscopic specimens of the tumor showed a small blue round-cell tumor. Immunohistochemistry showed cells to be negative for cytokeratin AE1/3, desmin, myogenin, CD10, CD34, and CD99, focal positive for vimentin, and positive for muscle-specific actin (HHF-35), neurofilament, synaptophysin and CD56. Fluorescence in situ hybridization revealed no split signal showing Ewing sarcoma breakpoint region 1 gene translocation. Deletion of 1p36 was identified in 30% of the tumor cells. These findings are thought to be equivalent to central type primitive neuroectodermal tumors/neuroblastoma. Cytoreductive debulking surgery followed by chemotherapy, including cyclophosphamide, vincristine and adriamycin, resulted in complete remission. She has no evidence of disease at 24 months after surgery.

  11. 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

  12. 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.

  13. Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata.

    Science.gov (United States)

    Rieser, M J; Gu, Z M; Fang, X P; Zeng, L; Wood, K V; McLaughlin, J L

    1996-02-01

    Bioactivity-directed fractionation of the seeds of Annona muricata L. (Annonaceae) resulted in the isolation of five new compounds: cis-annonacin (1), cis-annonacin-10-one (2), cis-goniothalamicin (3), arianacin (4), and javoricin (5). Three of these (1-3) are among the first cis mono-tetrahydrofuran ring acetogenins to be reported. NMR analyses of published model synthetic compounds, prepared cyclized formal acetals, and prepared Mosher ester derivatives permitted the determinations of absolute stereochemistries. Bioassays of the pure compounds, in the brine shrimp test, for the inhibition of crown gall tumors, and in a panel of human solid tumor cell lines for cytotoxicity, evaluated relative potencies. Compound 1 was selectively cytotoxic to colon adenocarcinoma cells (HT-29) in which it was 10,000 times the potency of adriamycin.

  14. Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata.

    Science.gov (United States)

    Zeng, L; Wu, F E; Oberlies, N H; McLaughlin, J L; Sastrodihadjo, S

    1996-11-01

    Bioactivity-directed fractionation of the leaves of Annona muricata resulted in the isolation of annopentocins A (1), B (2), and C(3), and cis- and trans-annomuricin-D-ones (4, 5). Compounds 1-3 are the first acetogenins reported bearing a mono-tetrahydrofuran (THF) ring with one flanking hydroxyl, on the hydrocarbon side, and another hydroxyl, on the lactone side, that is one carbon away from the THF ring. Compounds 4 and 5 were obtained in a mixture and are new mono-THF ring acetogenins bearing two flanking hydroxyls and an erythro-diol located between the THF and the ketolactone rings. Compound 1 was selectively cytotoxic to pancreatic carcinoma cells (PACA-2), and 2 and 3 were selectively cytotoxic to lung carcinoma cells (A-549); the mixture of 4 and 5 was selectively cytotoxic for the lung (A-549), colon (HT-29), and pancreatic (PACA-2) cell lines with potencies equal to or exceeding those of Adriamycin.

  15. Interaction of ionizing radiation, genetically active chemicals, and radiofrequency radiation in human and rodent cells. Final report 1 Oct 87-30 Sep 89

    Energy Technology Data Exchange (ETDEWEB)

    Meltz, M.L.; Holahan, P.K.; Smith, S.T.; Kerbacher, J.J.; Ciaravino, V.

    1990-12-01

    The purpose of this project was to investigate the possible interaction between radiofrequency radiation (RFR) and agents which are known to damage DNA. Experiments were performed using exposures of CHO cells to 350, 850, 1200, and 2450 MHz RFR at up to 40 W/kg and temperatures ranging from 37 to 40 C. No genotoxic effect was observed by sister chromotid exchange induction, chromosome aberration induction, or gene mutation (at the thymidine kinase locus). At levels at or below 10 mW/cm2 and specific absorption rates (SARs) at or below 4 W/kg, there was no evidence that DNA repair was induced or repair of preexisting DNA damage was inhibited. Adriamycin but not mitomycin c caused a statistically significant increase in the frequency of aberrant cells at 40 C with or without RFR. These observations support thermal mechanisms of RFR interaction.

  16. 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.

  17. 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.

  18. 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......-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) × 4 →classical cyclophosphamide, methotrexate......, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m(2)) × 3 → docetaxel (T) (100 mg/m(2)) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) × 4 →CMF. The primary comparison evaluated docetaxel...

  19. Malignant peripheral nerve sheath tumour of penis.

    Science.gov (United States)

    Kaur, J; Madan, R; Singh, L; Sharma, D N; Julka, P K; Rath, G K; Roy, S

    2015-04-01

    Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin.

  20. Primary hepatic malignant peripheral nerve sheath tumor successfully treated with combination therapy: a case report and literature review

    Science.gov (United States)

    Jung, Hae Il; Lee, Hyoung Uk; Ahn, Tae Sung; Lee, Jong Eun; Lee, Hyun Yong; Cho, Hyon Doek; Lee, Sang Cheol

    2016-01-01

    Primary malignant peripheral nerve sheath tumor (MPNST) in a young female patient, not associated with neurofibromatosis type-I is extremely rare in the liver. A 33-year-old female was admitted with a right flank pain for a weak. The CT scan showed 12.5-cm-sized mass located at the right hepatic lobe. At laparotomy, about 20.0-cm-sized mass was on the right hepatic lobe with attachment to right diaphragmatic pleura. Right hepatic lobe and adherent part of diaphragmatic pleura were resected. On histology and immunohistochemistry, it was diagnosed MPNST. Adjuvant radiotherapy for the right diaphragmatic pleura and adjuvant chemotherapy with adriamycin, ifosfamide and cisplatin were sequentially performed. The prognosis of MPNST is generally poor and it is associated with a highly aggressive course of recurrence, metastases, and death. Our case is probably a first report about combination therapy. PMID:27904856

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

    Energy Technology Data Exchange (ETDEWEB)

    Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

    2000-06-01

    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 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/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)

  2. Total Synthesis of a Highly Potent Anticancer Natural Product OSW-1

    Institute of Scientific and Technical Information of China (English)

    Zhendong; Jin

    2001-01-01

    OSW-1 (1) and its four natural analogs (2-5) are five highly potent anticancer natural products that were recently isolated from the bulbs of Ornithogalum saundersiae, a perennial grown in southern Africa (Figure 1).1 The IC50 values of these compounds against human promyelocytic leukemia HL-60 cells range from between 0.1 to 0.3 nM.2 Their anticancer activities are from 10 to 100 times more potent than other well-known anticancer agents in clinical use, including mitomycin C, adriamycin, cisplatin, camptothecin, and taxol. OSW-1 (1), the main constituent of Ornithogalum saundersiae bulbs, is highly cytostatic in the NCI 60-cell in vitro screen, with a mean IC50 of 0.78 nM. It also looks promising from in vivo tests against mouse P388 leukemia (increased life span 59%) by a one-time administration of 0.01 mg/kg.  ……

  3. 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)

  4. Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization

    Science.gov (United States)

    2007-04-01

    5 hT R2 -.7 5 Cell Line...AdriamycinDosage (μM) C el l C ou nt (x 1 0, 00 0) MC F-0 MC F-. 02 MC F-. 08 MC F-. 25 MC F-. 75 hT R2 -0 hT R2 -.0 2 hT R2 -.0 8 hT R2 -.2 5 hT R2 -.7 5 * 0 10...MC F-. 75 hT R2 -0 hT R2 -.0 2 hT R2 -.0 8 hT R2 -.2 5 hT R2 -.7 5 0 5 10 15 20 25 30 35 Day 2 Day 4 * * D A PI TU N EL * * * * * * Figure

  5. 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.

  6. 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.

  7. Radioimmunoassay for aclacinomycin A.

    Science.gov (United States)

    Matsuzawa, Y; Kiyosaki, T; Oki, T; Takeuchi, T; Umezawa, H

    1982-04-01

    An antibody against aclacinomycin A (ACM) was produced in a rabbit by immunization with ACM-bovine serum albumin conjugate. The radioimmunoassay (RIA) was based on the competition of unlabeled anthracycline with 3H-labeled ACM for binding sites on a specific antibody. Antibody-bound and free antigen were separated by selective adsorption on dextran-coated charcoal. The antibody reacted equally with ACM and its metabolites, MA144 M1, MA144 S1 and aklavin, and could precisely distinguish aklavinone-related aglycones, adriamycin and daunomycin. RIA was sensitive in the range of 1 approximately 10 pmol per assay. The quantities of ACM and its metabolites in human plasma were practically determined without any pretreatment of physiological samples.

  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. Primary retroperitoneal transitional cell carcinoma presenting as a dumb-bell tumour.

    Science.gov (United States)

    Basu, S; Ansari, M; Gupta, S; Kumar, A

    2009-11-01

    We report a retroperitoneal transitional cell carcinoma arising from the primitive urogenital remnants of a 56-year-old married Indian woman. She presented with a huge cystic mass in the hypogastrium and right iliac fossa, which extended into the right thigh as a massive dumb-bell tumour. On exploration, it was found not to be arising from any known retroperitoneal structure. The mass was excised, and the histopathology confirmed transitional cell carcinoma with positive margins. Though she received postoperative chemotherapy with cyclophosphamide, adriamycin and cisplatin, she developed extensive local recurrence and hepatic secondaries, and succumbed to the disease after ten months of follow-up. We highlight the rarity of the disease, its atypical presentation as a cystic dumb-bell lump, its diagnostic challenges and aggressive behaviour, and review the literature on primary retroperitoneal transitional cell carcinomas.

  10. Reversing multidrug resistance by RNA interference through the suppression of MDR1 gene in human hepatoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Chen; Qi wang; Jian Guan; Zhi-Yong Huang; Wan-Guang Zhang; Bi-Xiang Zhang

    2006-01-01

    AIM: To reverse the multidrug resistance (MDR) by RNA interference (RNAi)-mediated MDR1 suppression in hepatoma cells.METHODS: For reversing MDR by RNAi technology, two different short hairpin RNAs (shRNAs) were designed and constructed into pGenSil-1 plasmid, respectively. They were then transfected into a highly adriamycin-resistant HepG2 hepatoma cell line (HepG2/ADM). The RNAi effect on MDR was evaluated by real-time PCR, cell cytotoxicity assay and rhodamine 123 (Rh123) efflux assy.RESULTS: The stably-transfected clones showed various degrees of reversal of MDR phenotype. Surprisingly, the MDR phenotype was completely reversed in two transfected clones.CONCLUSION: MDR can be reversed by the shRNAmediated MDRI suppression in HepG2/ADM cells, which provides a valuable clue to make multidrug-resistant hepatoma cells sensitive to anti-cancer drugs.

  11. Chrysin and its emerging role in cancer drug resistance.

    Science.gov (United States)

    Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandana C; Gogoi, Ranadeep

    2015-07-05

    This letter illustrates the significant chemosensitizing effects of chrysin to resistance cancer cells and refers to the article on "Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53" by Li et al., published in your journal recently. Recent studies have demonstrated that chrysin is able to sensitize or kill cancer cells which are resistant to chemotherapeutic drugs such as cisplatin, doxorubicin and adriamycin. Owing to its potential anti-cancer effects and devoid of toxicity to non-transformed cells, further research is required to completely explore its chemosensitizing effects in other cancers and also assess and evaluate its safety, before going for possible human application.

  12. 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.

  13. [Effects of the expression of mouse metallothionein-I gene in human HeLa cell line on drug resistance].

    Science.gov (United States)

    Li, X; Lü, W; Yin, S; Li, L

    2000-07-01

    Metallothionein-I (MT-I) gene was inserted into EcoRI site by using pSV2-neo plasmid vector. Recombiant plasmid was transfected into HeLa cells by DNA-calcium phosphate precipitation technique. MT-I expression colones were growing in medium including G418. The amount of MT-I expression in transfected cells was found 2.6 times higher than that of non-transfected ones. In order to observe the relationship between the expression of MT-I gene in cells and drug resistance, cells were treated with different concentrations of cisplatin and adriamycin respectively. The results indicated that cisplatin (0.1 mumol/ml) inhibited the growth of both transfected and non-transfected cells. The inhibitory rates were 34% and 82% respectively(P 0.05). The results indicated that MT was related to drug resistance of tumor cells.

  14. Total Synthesis of a Highly Potent Anticancer Natural Product OSW-1

    Institute of Scientific and Technical Information of China (English)

    Zhendong Jin; Wensheng Yu

    2001-01-01

    @@ OSW-1 (1) and its four natural analogs (2-5) are five highly potent anticancer natural products that were recently isolated from the bulbs of Ornithogalum saundersiae, a perennial grown in southern Africa (Figure 1).1 The IC50 values of these compounds against human promyelocytic leukemia HL-60 cells range from between 0.1 to 0.3 nM.2 Their anticancer activities are from 10 to 100 times more potent than other well-known anticancer agents in clinical use, including mitomycin C, adriamycin, cisplatin, camptothecin, and taxol. OSW-1 (1), the main constituent of Ornithogalum saundersiae bulbs, is highly cytostatic in the NCI 60-cell in vitro screen, with a mean IC50 of 0.78 nM. It also looks promising from in vivo tests against mouse P388 leukemia (increased life span 59%) by a one-time administration of 0.01 mg/kg.

  15. Anticancer Drug Resistance of HeLa Cells Transfected With Rat Glutathione S-transferase pi Gene

    Institute of Scientific and Technical Information of China (English)

    WEI CAO; JIN ZUO; YAN MENG; QIANG WEI; ZHAO-HU SHI; LI-MEI JU; FU-DE FANG

    2003-01-01

    Objective To establish a cytologic expressing system of rat glutathione S-transferase pi(GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods Theassessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum andvincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing ratGST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pimRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization usingDigoxin-labelled cDNA probe. Results HeLa/pSV-GT expressed significantly high degree ofGST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicitiesof HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drugconcentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin andcisplatinum were 70.13 μg/mL, 10.95 μg/mL and 16.52 μg/mL, respectively. In contrast, IC50 inHeLa/pSV-neo was 10.34 μg/mL, 7.48 μg/mL and 13.70 μg/mL, respectively. The cytotoxicities ofvincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. ConclusionsOur findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancerdrugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a usefulcytogenetic model for further research.

  16. Nephroprotective effect of heparanase in experimental nephrotic syndrome.

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    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.

  17. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  18. Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts.

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    Jian-Wei Wang

    Full Text Available There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE, area under the curve of wash-in (WiAUC, wash-in rate (WiR and wash-in perfusion index (WiPI were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI were noticed between adriamycin-treated and control groups (P0.05. Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001. Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.

  19. Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

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    Xiaomei Liu

    2016-07-01

    Full Text Available Background/Aims: Patients with esophageal atresia (EA and tracheoesophageal fistula (TEF often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. Methods: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1 were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. Results: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. Conclusions: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA-TEF lungs.

  20. 膀胱腫瘍に対する4'-epi-adriamycinの膀胱腔内注入療法に関する基礎的研究

    OpenAIRE

    津島, 知靖

    1985-01-01

    Adriamycin (ADM)の誘導体である4'-epi-adriamycin (EPI)を膀胱腔内注入療法に導入する目的で基礎的に検討した.1)人膀胱癌培養細胞株T24に対するEPIの殺細胞効果をcolony formation methodにて検討した.EPIはADMと比較してやや低い殺細胞効果を有していたが,mitomycin Cおよびaclacinomycin Aと比較して高い殺細胞効果を示した.2)ビーグル犬を用いて両側尿管皮膚瘻を施行し,空置した膀胱腔内にEPIを注入し血中,尿中および臓器内濃度をHPLC法にて測定した結果,EPIの膀胱壁よりの吸収量は少量であった.3)正常膀胱粘膜に対する影響について検討したが,薬剤を6時間把持した場合,EPI 20 mg/生塩水10 mlでは,まったく変化は認められず,EPI 50 mg/生塩水10 mlでは,粘膜の剥離が散在性に認められたのみであり,EPI 100 mg/生塩水10 mlでは粘膜下層に影響がおよんだ...

  1. Cinnamaldehyde Derivative (CB-PIC Sensitizes Chemo-Resistant Cancer Cells to Drug-Induced Apoptosis via Suppression of MDR1 and its Upstream STAT3 and AKT Signalling

    Directory of Open Access Journals (Sweden)

    Jianzhong Xi

    2015-03-01

    Full Text Available Background/Aims: Our group reported that cinnamaldehyde derivative, (E-4-((2-(3-oxopop-1-enylphenoxymethylpyridinium malonic acid (CB-PIC induced apoptosis in hypoxic SW620 colorectal cancer cells via activation of AMP-activated protein kinase (AMPK and extracellular signal regulated kinase (ERK. Herein, sensitizing effect of CB-PIC was investigated in resistant cancer cells such as paclitaxel (PT resistant lung cancer cells (H460/PT, and Adriamycin (Adr resistant breast cancer (MCF7/Adr and colon cancer (HCT15/cos cells. Methods: Various drug resistant cell lines were treated with CB-PIC, and the signalling pathway and functional assay were explored by Western blot, Rhodamine assay, FACS, RT-PCR and MTT assay. Results: We found that CB-PIC effectively exerted cytotoxicity, increased sub G1 population and the cleaved form of poly (ADP-ribose polymerase (PARP and caspase 9 in drug resistant cancer cells. Furthermore, CB-PIC sensitized resistant cancer cells to adriamycin via downregulation of survival proteins such as survivin, Bcl-xL and Bcl-2, along with MDR1 suppression leading to accumulation of drug in the intracellular region. Of note, CB-PIC transcriptionally decreased MDR1 expression via suppression of STAT3 and AKT signalling in three resistant cancer cells with highly expressed P-glycoprotein. Nonetheless, CB-PIC did not affect transport activity of P-glycoprotein in a short time efflux assay, while epigallocatechin gallate (EGCG accumulated Rhodamine 123 into intracellular region of cell by direct inhibition of MDR1 transport activity. Conclusions: These data demonstrate that CB-PIC suppresses the P-glycoprotein expression through inhibition of STAT3 and AKT signalling to overcome drug resistance in chemo-resistant cancer cells as a potent chemotherapeutic sensitizer.

  2. 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.

  3. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study.

    Directory of Open Access Journals (Sweden)

    Daniela Caronia

    Full Text Available BACKGROUND: Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. METHODOLOGY/PRINCIPAL FINDINGS: In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs and 2 Copy Number Variants (CNVs in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1×10⁻⁵, and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9×10⁻⁵, rs1128503 and rs10276036 (r² = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9×10⁻⁵. Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] ≤ 0.03. CONCLUSIONS: Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy.

  4. Knockdown of nucleophosmin by RNA interference reverses multidrug resistance in resistant leukemic HL-60 cells.

    Science.gov (United States)

    Lin, Minhui; Hu, Jianda; Liu, Tingbo; Li, Jing; Chen, Buyuan; Chen, Xinji

    2013-09-01

    Nucleophosmin, a multifunctional nucleolar phosphoprotein, is involved in many cellular activities. However, the role of NPM in drug-resistance of leukemia has not yet been explored. We designed and selected one shRNA targeting on NPM gene transduction into HL-60 and HL-60/ADR cell lines (an adriamycin resistant cell line) by lentivirus. Cell proliferation, apoptosis and differentiation were assessed. The expressions of the related genes and proteins were detected by real-time quantitative RT-PCR and Western blotting. The results showed obvious down-regulation of NPM mRNA and protein levels after NPM RNAi. NPM-targeted RNAi also resulted in many cellular changes, such as, suppressing cell proliferation and inducing cell differentiation. Down-regulation of NPM gene could arrest the cell cycle progression, an increase in the proportion of G0/G1 phase in knockdown groups. NPM gene silencing could also induce pro-apoptotic genes and proteins expression, and inhibit anti-apoptotic genes/proteins expression. Furthermore, IC50 of two chemotherapeutic agents (adriamycin and ADR; daunorubicin and DNR) to HL-60 and HL-60/ADR cells decreased, especially more remarkable on HL-60/ADR cells. IC50 of ADR on HL-60/ADR cells was reduced from 12.544 ± 0.851 μmol/L (before NPM RNAi) to 6.331 ± 0.522 μmol/L (after NPM RNAi), IC50 of DNR was reduced from 2.152 ± 0.143 μmol/L (before NPM RNAi) to 1.116 ± 0.093 μmol/L (after NPM RNAi). The relative reversal rate of HL-60/ADR cells on ADR was 50.2%, and on DNR was 48.9%. In conclusion, our results demonstrated that shRNA expression vectors could effectively reduce NPM expression and restore the drug sensitivity of resistant leukemic cells to conventional chemotherapeutic agents.

  5. Anticancer efficacy and absorption, distribution, metabolism, and toxicity studies of Aspergiolide A in early drug development

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-10-01

    Full Text Available Yuanyuan Wang, Xin Qi, Dehai Li, Tianjiao Zhu, Xiaomei Mo, Jing LiKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of ChinaAbstract: Since the first anthracycline was discovered, many other related compounds have been studied in order to overcome its defects and improve efficacy. In the present paper, we investigated the anticancer effects of a new anthracycline, aspergiolide A (ASP-A, from a marine-derived fungus in vitro and in vivo, and we evaluated the absorption, distribution, metabolism, and toxicity drug properties in early drug development. We found that ASP-A had activity against topoisomerase II that was comparable to adriamycin. ASP-A decreased the growth of various human cancer cells in vitro and induced apoptosis in BEL-7402 cells via a caspase-dependent pathway. The anticancer efficacy of ASP-A on the growth of hepatocellular carcinoma xenografts was further assessed in vivo. Results showed that, compared with the vehicle group, ASP-A exhibited significant anticancer activity with less loss of body weight. A pharmacokinetics and tissue distribution study revealed that ASP-A was rapidly cleared in a first order reaction kinetics manner, and was enriched in cancer tissue. The maximal tolerable dose (MTD of ASP-A was more than 400 mg/kg, and ASP-A was not considered to be potentially genotoxic or cardiotoxic, as no significant increase of micronucleus rates or inhibition of the hERG channel was seen. Finally, an uptake and transport assay of ASP-A was performed in monolayers of Caco-2 cells, and ASP-A was shown to be absorbed through the active transport pathway. Altogether, these results indicate that ASP-A has anticancer activity targeting topoisomerase II, with a similar structure and mechanism to adriamycin, but with much lower toxicity. Nonetheless, further molecular structure optimization is necessary.Keywords: aspergiolide A, anticancer

  6. 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

  7. 2011~2013年南京市样本医院抗肿瘤抗生素应用现状和趋势分析%Status and Tendency of Anticancer Antibiotics from 2011 to 2013 in Nan-jing Sample Hospitals

    Institute of Scientific and Technical Information of China (English)

    彭苗苗; 方芸; 刘慧

    2014-01-01

    Objective: To comprehend the new therapeutic idea and way of using new drugs by estimating the using situation of anticancer antibiotics from 2011 to 2013 in 27 sample hospitals of Nanjing. Methods: With the method of defined daily dose (DDDs), the use of anticancer antibiotics was analyzed in respect of drug categories, consumption quantity, sales amount, DDDs and defined daily consumption (DDC), etc., from 2011 to 2013 in 27 sample hospitals. Results: The sales amount of anticancer antibiotics increased year by year, and the most commonly used drugs were antharcycline. The top four sales amounts were pharmorubicin, idarubicin, pirarubicin and adriamycin, the top four DDDs were pharmorubicin, pirarubicin, mitomycin and adriamycin. Most of the anticancer antibiotics sales amounts and the DDDs were concordant. Conclusion: The demand of anticancer antibiotics increased year by year. They have broad development prospects, especially antharcycline will become the leading anticancer antibiotics..%目的:评价南京地区27家样本医院2011~2013年抗肿瘤抗生素使用情况及特点,了解抗肿瘤抗生素治疗新理念和应用新药的新途径。方法:用限定日剂量法(DDDs)分析2011~2013年样本医院抗肿瘤抗生素应用的品种、数量、金额、日均用量数(DDDs)及日均费用(DDC)等情况。结果:抗肿瘤抗生素销售金额及销量逐年上升,最常用的是蒽环类抗肿瘤抗生素,已成为抗肿瘤抗生素的主体,销售金额排名前几位的药物主要是表柔比星、伊达比星、吡柔比星和阿霉素;DDDs排名前几位的药物主要是表柔比星、吡柔比星、丝裂霉素和阿霉素。大多数抗肿瘤抗生素的销量与使用同步性良好。结论:抗肿瘤抗生素的需求量逐年增加,尤其是蒽环类药物成为抗肿瘤抗生素的主流药物。

  8. Synthesis, characterization of novel injectable drug carriers and the antitumor efficacy in mice bearing Sarcoma-180 tumor.

    Science.gov (United States)

    Guo, Wen-xun; Huang, Kai-xun; Tang, Rong; Xu, Hui-bi

    2005-10-20

    New unsaturated polyesters of poly(fumaric acid-glycol-dodecanedioic acid) P(FA-GLY-DDDA) copolymers, poly(fumaric acid-glycol-brassylic acid) P(FA-GLY-BA) copolymers, poly(fumaric acid-glycol-tetradecanedioic acid) P(FA-GLY-TA) copolymers and poly(fumaric acid-glycol-pentadecanedioic acid) P(FA-GLY-PA) copolymers were prepared by melt polycondensation of the corresponding mixed monomers: fumaric acid, glycol and one of C(12-15) dibasic acids. The copolymers were characterized by FT-IR, gel permeation chromatography (GPC), and the surface structure of unsaturated polyesters after solidify were studied by atomic force microscopy (AFM). The molecular structure and composition of the unsaturated polyesters were determined by 1H NMR spectroscopy. In vitro studies showed that some of the copolymers are degradable in phosphate buffer at 37 degrees C and have properly drug release rate as drug carriers. The biocompatibility of P(FA-GLY-DDDA) and P(FA-GLY-BA) copolymers under mice skin was also evaluated, macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(FA-GLY-DDDA) copolymers and P(FA-GLY-BA) copolymers containing 5% adriamycin hydrochloride (ADM) in mice bearing Sarcoma-180 tumor exhibited increased volume doubling time (VDT) (22+/-1.5 days and 24+/-2.5 days) compared to plain subcutaneous injection of ADM (7+/-0.9 days). The antitumor efficacy of injecting P(FA-GLY-DDDA)-ADM inside tumor twice intervened in 22 days exhibited an especially increased cytotoxic effect as revealed by increased VDT (33+/-2.5 days), and the antitumor efficacy of injecting P(FA-GLY-BA)-ADM inside tumor twice intervened in 24 days exhibited an especially increased cytotoxic effect as revealed by increased VDT (35+/-1.5 days). The studies suggested that P(FA-GLY-DDDA) copolymers and P(FA-GLY-BA) copolymers as effective and injectable carriers for antineoplastic drug like adriamycin hydrochloride

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

    Science.gov (United States)

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

    2009-08-01

    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 mechanism 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% inhibitory 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 arabinosylcytosine, 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 nucleofected 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 (nucleofected 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 arabinosylcytosine. Down-regulating the SKP2 expression and arresting cells in the G0/G1 phase improve drug sensitivity of leukemia cells with down-regulated MRP expression.

  10. P-糖蛋白抑制剂HZ08对裸鼠体内肿瘤多药耐药逆转以及对大鼠肝P450酶影响%Effects of HZ08,a novel P-glycoprotein inhibitor, on the reversal of P-glyco-protein mediated multidrug resistance in nude mice and cytochrome P-450 ac-tivities in rat liver microsomes

    Institute of Scientific and Technical Information of China (English)

    严方; 李运曼; 王秋娟; 方伟蓉; 康恺; 张陆勇

    2008-01-01

    目的:考察P-糖蛋白抑制剂HZ08 对K562/ADM接种裸鼠体内肿瘤多药耐药的逆转作用及HZ08对大鼠肝P450酶亚型的影响.方法:K562/ADM接种的裸鼠尾静脉注射HZ08和阿霉素4周,与对照组和阳性药组比较瘤重;HZ08与CYP450亚型特异性底物在大鼠肝微粒体中温孵,与对照组比较测定HZ08 对于CYP450亚型的影响.结果:HZ08可显著减小裸鼠体内的瘤重,并对大鼠肝微粒体CYP3A4有较弱的抑制作用,对其他P450酶亚型无显著抑制作用.结论:HZ08在裸鼠体内具有较好的逆转P-糖蛋白介导的肿瘤多药耐药的作用,并且在体外实验中对P450酶具有较小的影响.%Aim: To evaluate the effects of HZ08, a novel P-glycoprotein inhibitor, on reversing tumor resistance of K562/ADM to adriamycin in nude mice and on the activities of cytochromes P-450 (GYP) isoforms. Methods: Nude mice bearing K562/ADM were injected at different doses of HZ08 with adriamycin for 4 weeks. The tumor weights of HZ08 treatment groups were determined and compared to those of the control and positive groups. In addition, the effects of HZ08 were examined on GYP isoforms-mediated metabolism of specific substrates by GYP isoforms in rat liver microsomes in the presence or absence of HZ08. Results: The tumor weights of HZ08 treatment groups were significantly decreased and HZ08 was a relatively potent inhibitor of CYP3A4, with no significant effects on other isoforms tested. Conclusion: HZ08 has potent effects on reversing P-glycoprotein mediated tumor multidrug resistance in rive with little influence on cytoehrome P-450 activities of rat liver.

  11. 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

  12. An ultrasensitive electrochemical DNA biosensor based on a copper oxide nanowires/single-walled carbon nanotubes nanocomposite

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Mei [Key Laboratory of Biorheology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Hou, Changjun, E-mail: houcj@cqu.edu.cn [Key Laboratory of Biorheology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); National Key Laboratory of Fundamental Science of Micro/Nano-Device and System Technology, Chongqing University, Chongqing 400044 (China); Huo, Danqun [Key Laboratory of Biorheology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); National Key Laboratory of Fundamental Science of Micro/Nano-Device and System Technology, Chongqing University, Chongqing 400044 (China); Yang, Mei [Key Laboratory of Biorheology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Fa, Huanbao [College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044 (China)

    2016-02-28

    Graphical abstract: A novel and sensitive electrochemical biosensor based on hybrid nanocomposite consisting of copper oxide nanowires (CuO NWs) and carboxyl-functionalized single-walled carbon nanotubes (SWCNTs-COOH) was first developed for the detection of the specific-sequence target DNA. This schematic represents the fabrication procedure of our DNA biosensor. - Highlights: • An ultrasensitive DNA electrochemical biosensor was developed. • CuO NWs entangled with the SWCNTs formed a mesh structure with good conductivity. • It is the first time use of CuONWs-SWCNTs hybrid nanocomposite for DNA detection. • The biosensor is simple, selective, stable, and sensitive. • The biosensor has great potential for use in analysis of real samples. - Abstract: Here, we developed a novel and sensitive electrochemical biosensor to detect specific-sequence target DNA. The biosensor was based on a hybrid nanocomposite consisting of copper oxide nanowires (CuO NWs) and carboxyl-functionalized single-walled carbon nanotubes (SWCNTs-COOH). The resulting CuO NWs/SWCNTs layers exhibited a good differential pulse voltammetry (DPV) current response for the target DNA sequences, which we attributed to the properties of CuO NWs and SWCNTs. CuO NWs and SWCNTs hybrid composites with highly conductive and biocompatible nanostructure were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and cyclic voltammetry (CV). Immobilization of the probe DNA on the electrode surface was largely improved due to the unique synergetic effect of CuO NWs and SWCNTs. DPV was applied to monitor the DNA hybridization event, using adriamycin as an electrochemical indicator. Under optimal conditions, the peak currents of adriamycin were linear with the logarithm of target DNA concentrations (ranging from 1.0 × 10{sup −14} to 1.0 × 10{sup −8} M), with a detection limit of 3.5 × 10{sup −15} M (signal/noise ratio of 3). The biosensor also showed high

  13. Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: A prospective clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Mah, K.; Van Dyk, J.; Braban, L.E.; Hao, Y.; Keane, T.J. (Univ. of Toronto, Ontario (Canada)); Poon, P.Y. (Univ. of British Columbia (Canada))

    1994-02-01

    The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. DEF were measured by comparing the incidence of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation. 40 refs., 3 figs., 3 tabs.

  14. 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

  15. Effects of c-fos Down-regulation via shRNA on P-gp-mediated Multidrug Resistance in Human Breast Cancer MCF-7/ADR Cells%shRNA抑制c-fos表达对P-gp介导的乳腺癌多药耐药的影响

    Institute of Scientific and Technical Information of China (English)

    师锐赞; 胡晓玲; 范彦英

    2012-01-01

    多药耐药(multidrug resistance,MDR)是导致化疗失败的重要原因,多药耐药基因(multidrug resistance gene,mdr1)产物P-糖蛋白(P-glycoprotein,P-gp)过表达是最主要的耐药机制.原癌基因c-fos在肿瘤MDR中的作用渐受重视.主要选用人乳腺癌敏感株MCF-7和阿霉素(adriamycin,ADR)筛选的、mdr1/P-gp高表达的耐药株MCF-7/ADR,探讨c-fos在P-gp介导的乳腺癌MDR中的作用.相对于MCF-7,c-fos在MCF-7/ADR高表达.采用shRNA法下调c-fos表达后,MCF-7/ADR对ADR的敏感性大大增强,且mdr1/P-gp表达减少、P-gp外排功能降低.c-fos表达下调可逆转对P-gp介导的乳腺癌MDR的实验结果,为c-fos成为逆转肿瘤耐药诊断和治疗的新靶标,对实现耐药乳腺癌的分子靶向治疗提供了理论基础.%Multidrug resistance (MDR) is the main reason of chemotherapy failure. The overexpression of P-glycoprotein (P-gp) , encoded by the multidrug resistance (mdrl) gene, is thought to be the major cause of MDR phenotype. Since much attention has been paid to the role of proto-oncogene c-fos in MDR, adriamycin (ADR)-selected resistant breast cancer cells (MCF-7/ADR) with mdrl/P-gp overexpression and parental drug-sensitive cells ( MCF-7) were chosen to analyze the role of c-fos in P-gp-mediated MDR. Elevated c-fos expression is observed in MCF-7/ADR compared to MCF-7 cells. Down-regulation of c-fos expression via shRNA resulted in sensitization of MCF-7/ADR cells to ADR and decreased the expression of mdrl/P-gp and efflux function of P-gp. Based on these results, c-fos may represent a potential molecular target for resistant cancer therapy, and suppressing c-fos gene expression may therefore be an effective means for targeted molecular therapy.

  16. HDAC inhibitor sodium butyrate sensitizes E1A+Ras-transformed cells to DNA damaging agents by facilitating formation and persistence of γH2AX foci.

    Science.gov (United States)

    Abramova, Maria V; Svetlikova, Svetlana B; Kukushkin, Alexander N; Aksenov, Nikolai D; Pospelova, Tatiana V; Pospelov, Valery A

    2011-12-15

    HDAC inhibitors (HDACi) suppress the growth of tumor cells due to induction of cell cycle arrest, senescence or apoptosis. Recent data demonstrate that HDACi can interfere with DNA Damage Response (DDR) thereby sensitizing the cells to DNA damaging agents. Here, we show that HDACi sodium butyrate (NaBut) potentiates the formation of γH2AX foci predominantly in S-phase E1A+Ras cells. Accumulation of γH2AX foci sensitizes the cells toward such DNA damaging agents as irradiation (IR) and adriamycin. In fact, NaBut potentiates the persistence of γH2AX foci induced by genotoxic agents. The synergizing effects depend on DNA damaging factors and on the order of NaBut treatment. Indeed, NaBut treatment for 24 h leads to an accumulation of G 1-phase cells and a lack of S-phase cells, therefore, adriamycin, a powerful S-phase-specific inhibitor, when added to NaBut-treated cells, is unable to substantially add γH2AX foci. In contrast, IR produces both single- and double-strand DNA breaks at any stage of the cell cycle and was shown to increase γH2AX foci in NaBut-treated cells. Further, a lifetime of IR-induced γH2AX foci depends on the subsequent presence of HDACi. Correspondingly, NaBut withdrawal leads to the extinction of IR-induced γH2AX foci. This necessitates HDACi to hold the IR-induced γH2AX foci unrepaired. However, the IR-induced γH2AX foci persist after long-term NaBut treatment (72 h) even after washing the drug. Thus, although signaling pathways regulating H2AX phosphorylation in NaBut-treated cells remain to be investigated, the obtained results show that NaBut potentiates effects of DNA damaging agents by facilitating formation and persistence of γH2AX foci.

  17. Methylation-regulated miR-149 modulates chemoresistance by targeting GlcNAc N-deacetylase/N-sulfotransferase-1 in human breast cancer.

    Science.gov (United States)

    He, Dong-Xu; Gu, Xiao-Ting; Li, You-Ran; Jiang, Li; Jin, Jian; Ma, Xin

    2014-10-01

    Dysregulation of microRNA is strongly implicated in the chemoresistance of cancer. In this study, we found that miR-149 was downregulated and involved in chemoresistance in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM). Downregulation of miR-149 was related to hypermethylation of its 5'-UTR; this methylation also affected the expression of the glypican 1 gene, which is both the host and the target gene of miR-149. Furthermore, we found that miR-149 modulated chemoresistance through targeting the expression of GlcNAc N-deacetylase/N-sulfotransferase-1 (NDST1). With downregulated miR-149, NDST1 expression was increased in chemoresistant MCF-7/ADM cells versus control MCF-7 wild-type cells. The increased NDST1 then activated a heparan sulfate-related pathway involving activation of heparanase. Finally, expression of miR-149 and NDST1 was confirmed in clinical chemoresistant samples of breast cancers receiving anthracycline/taxane-based chemotherapies. The high expression of NDST1 was also an unfavorable predictor for distant relapse-free survival in Her2 and basal breast cancers. Taken together, our findings demonstrate that miR-149 is regulated by methylation, and is a modulator of cancer chemoresistance by targeting NDST1.

  18. MicroRNA-498 Inhibition Enhances the Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Podocyte-Like Cells.

    Science.gov (United States)

    Zhang, Lina; Li, Kanghua; Yan, Xi; Liang, Xiaolei; Wang, Shihua; Han, Qin; Zhao, Robert Chunhua

    2015-12-15

    Podocyte depletion is a key event in the progression of end-stage kidney disease (ESKD) resulting in nephrotic proteinuria and renal failure, but the treatment options are limited to dialysis and renal transplantation. So there is an urgent need for renal regenerative therapies. Generation of podocytes from human stem cells is regarded as a promising therapeutic strategy to repair or regenerate the damaged kidneys; however, the reliable induction system remains a challenge. In this study, we established a two-stage induction protocol for podocyte generation from human adipose-derived mesenchymal stem cells (hAD-MSCs). We initially established a condition that induces hAD-MSCs toward intermediate mesoderm cells with activin A and high concentration of retinoic acid (RA). Subsequently, by using the combination of activin A and low concentration of RA and BMP7, we generated podocyte-like cells expressing multiple podocyte-specific markers and able to integrate into a developing nephron of embryonic kidney explant culture and ameliorate proteinuria and kidney injure in adriamycin-treated mice. Furthermore, we identified that miRNA-498 inhibitor has potential to improve the differentiation of hAD-MSCs into podocyte-like cells and established a robust induction protocol. Thereby, our study advocated an efficient method for the induction of kidney podocyte-like (iPod) cells from hAD-MSCs and provided an ideal candidate for regenerative therapies of the kidney.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. ADM与5Fu可抑制MDA-MB231乳癌细胞的SNCG表达%ADM and 5Fu inhibit the synuclein-γexpression of MDA-MB231 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    袁光波; 张幸平; 何金花; 唐卫军; 陈睿

    2008-01-01

    目的 研究乳癌临床常用化疗药物顺铂(ciaplalin or DDP),阿霉素(adriamycin,ADM),氟尿嘧啶(fluorouradl,5Fu)对MDA-MB231乳癌细胞SNCG表达的干扰效应.方法 通过RT-PCR及免疫组织化学法检测上述药物处理组和阴性对照组MDA-MB231细胞的SNCG表达状况,用Quantity One软件及北航真彩色医学图像处理系统(CM-20008)分别对各组SNCG mR-NA和蛋白相对表达水平进行分析.结果 ADM和5Fu处理组与阴性对照组比较,MDA-MB231细胞的SNCG mRNA及蛋白表达水平差异均有统计学意义(P值均小于0.05),而DDP处理组表达水平与对照组无差别.结论 ADM和5Fu可抑制MDA-MB231细胞的SNCG表达.

  1. Human C6orf211 Encodes Armt1, a Protein Carboxyl Methyltransferase that Targets PCNA and Is Linked to the DNA Damage Response

    Directory of Open Access Journals (Sweden)

    J. Jefferson P. Perry

    2015-03-01

    Full Text Available Recent evidence supports the presence of an L-glutamyl methyltransferase(s in eukaryotic cells, but this enzyme class has been defined only in certain prokaryotic species. Here, we characterize the human C6orf211 gene product as “acidic residue methyltransferase-1” (Armt1, an enzyme that specifically targets proliferating cell nuclear antigen (PCNA in breast cancer cells, predominately methylating glutamate side chains. Armt1 homologs share structural similarities with the SAM-dependent methyltransferases, and negative regulation of activity by automethylation indicates a means for cellular control. Notably, shRNA-based knockdown of Armt1 expression in two breast cancer cell lines altered survival in response to genotoxic stress. Increased sensitivity to UV, adriamycin, and MMS was observed in SK-Br-3 cells, while in contrast, increased resistance to these agents was observed in MCF7 cells. Together, these results lay the foundation for defining the mechanism by which this post-translational modification operates in the DNA damage response (DDR.

  2. The protective role of curcumin in cardiovascular diseases.

    Science.gov (United States)

    Wongcharoen, Wanwarang; Phrommintikul, Arintaya

    2009-04-01

    Curcumin (diferuloylmethane) is a polyphenol responsible for the yellow color of the curry spice turmeric. It has been used in a variety of diseases in traditional medicine. Modern scientific research has demonstrated its anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-thrombotic, and cardiovascular protective effects. In this review, we focused mainly on the effects of curcumin on the cardiovascular system. The antioxidant effects of curcumin have been shown to attenuate adriamycin-induced cardiotoxicity and may prevent diabetic cardiovascular complications. The anti-thrombotic, anti-proliferative, and anti-inflammatory effects of curcumin and the effect of curcumin in decreasing the serum cholesterol level may protect against the pathological changes occurring with atherosclerosis. The p300-HAT inhibitory effects of curcumin have been demonstrated to ameliorate the development of cardiac hypertrophy and heart failure in animal models. The inflammatory effects of curcumin may have the possibility of preventing atrial arrhythmias and the possible effect of curcumin for correcting the Ca(2+) homeostasis may play a role in the prevention of some ventricular arrhythmias. The preclinical studies from animal to clinical data in human are discussed.

  3. Cyclo-oxygenase 2 inhibitor, nabumetone, inhibits proliferation in chronic myeloid leukemia cell lines.

    Science.gov (United States)

    Vural, Filiz; Ozcan, Mehmet Ali; Ozsan, Güner Hayri; Ateş, Halil; Demirkan, Fatih; Pişkin, Ozden; Undar, Bülent

    2005-05-01

    The anti-tumor effect of cyclo-oxygenase (COX) inhibitors has been documented in several studies. COX2 inhibitors have attracted more attention because of the fewer side-effects and the more prominent anti-tumor effects. However, experience with these drugs in hematological malignancies is limited. In our study, a potent COX2 inhibitor, nabumetone (NBT), was investigated for its anti-proliferative and apoptotic effects in K-562 and Meg-01 chronic myeloid leukemia blastic cell lines as a single agent or in combination with adriamycin (ADR) and interferon alpha (IFN-a). In these cell lines, a dose-dependent inhibition of proliferation was observed with NBT. We observed no significant apoptotic effect of NBT. However, NBT potentiated the apoptotic effect of ADR in the K-562 cell line. Bcl-2 expression was reduced by NBT (11% vs. 2%). The combination of NBT with IFN did not have any significant effect on the K-562 cell line. We suggest that NBT inhibits proliferation and potentiates the apoptotic effect of ADR in chronic myeloid leukemia cell lines.

  4. 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.

  5. 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.

  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.

  7. A Novel Strategy for Inducing the Antitumor Effects of Triterpenoid Compounds: Blocking the Protumoral Functions of Tumor-Associated Macrophages via STAT3 Inhibition

    Directory of Open Access Journals (Sweden)

    Yukio Fujiwara

    2014-01-01

    Full Text Available There are many types of nontumor cells, including leukocytes, fibroblasts, and endothelial cells, in the tumor microenvironment. Among these cells, infiltrating macrophages have recently received attention as novel target cells due to their protumoral functions. Infiltrating macrophages are called tumor-associated macrophages (TAMs. TAMs polarized to the M2 phenotype are involved in tumor development and are associated with a poor clinical prognosis. Therefore, the regulation of TAM activation or M2 polarization is a new strategy for antitumor therapy. We screened natural compounds possessing an inhibitory effect on the M2 polarization of human macrophages. Among 200 purified natural compounds examined, corosolic acid (CA and oleanolic acid (OA, both are categorized in triterpenoid compounds, inhibited macrophage polarization to M2 phenotype by suppressing STAT3 activation. CA and OA also directly inhibited tumor cell proliferation and sensitized tumor cells to anticancer drugs, such as adriamycin and cisplatin. The in vivo experiments showed that CA significantly suppressed subcutaneous tumor development and lung metastasis in a murine sarcoma model. The application of triterpenoid compounds, such as CA and OA, is a potential new anticancer therapy targeting macrophage activation, with synergistic effects with anticancer agents.

  8. Ewing’s sarcoma of the maxillary sinus

    Directory of Open Access Journals (Sweden)

    Firas Nasser

    2015-07-01

    Full Text Available Ewing’s sarcoma is typically an aggressive, poorly differentiated tumor affecting children and young adults, it accounts for 4–6% of all primary bone tumors and facial primary localizations occur in only 1–4% of all cases, mostly in the mandible and calvaria. Paranasal sinus involvement is rare. A 22-year-old female was reviewed in Oral & Cranio Maxillofacial Surgery Department. She complained of swelling of the right paranasal area, of one-month duration, progressively increasing in size and associated with pain. The medical history was unremarkable, Contrast Enhanced Computed Tomography scan showed a destructive lesion of the anterior wall of the right maxillary sinus reaching up to the medial wall of the maxillary sinus, other paranasal sinus appearance was normal. Incisional biopsy proved it to be Ewing’s Sarcoma. She was treated by chemotherapy using Vincristine, Adriamycin, and Cyclophosphamide alternating with Etoposide & Ifosfamide and Radiotherapy, and this resulted in complete regression of the tumor. Repeated PET scans every 6 months did not suggest any recurrence of the right maxillary sinus tumor. We concluded that treatment by induction chemotherapy followed by radiation therapy leads to a favorable outcome in the above described case, avoiding the morbidity that can result from surgical options.

  9. 三氧化二砷逆转人胃癌细胞SGC7901/ADR耐药性的作用机制%Reversal mechanism of arsenic trioxide in the drug resistance of human gastric cancer cell line SGC7901/ADR

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the reversal effect of arsenic trioxide (As2O3) on the multidrug resistance of human gastric tumor SGC7901/ADR cell line to adriamycin (ADM) and its reversal mechanisms. Methods: The non-cytotoxic concentration of As2O3 and the sensitivity of SGC7901/ADR cells to ADM were detected by MTT assay. The drug concentration and P-gp function of SGC7901/ADR cells were measured with flow cytometry (FCM), and the impacts of As2O3 on the GST-π and TopoⅡ expressions of SGC7901/ADR cells were analyzed by immunohistochemical method. Results: As2O3 at 0.4 to 0.8 μmol/Lconcentrations were not significantly cytotoxic to SGC7901/ADR cells. As2O3 at 0.8 μmol/L could improve the sensitivity of SGC7901/ADR cells to ADM via inhibiting P-gp function, down-regulating GST-π expression and increasing the intracellular accumulation of ADM in SGC7901/ADR cells. Conclusion: As2O3 can reverse partly the drug-resistance of SGC7901/ADR cells to ADM, which may be related with inhibiting the P-gp function and down-regulating GST-π expression.

  10. Primitive neuroectodermal tumor of the liver: a case report.

    Science.gov (United States)

    Mani, Siddhartha; Dutta, Deep; De, Binay K

    2010-03-01

    Ewing sarcoma/primitive neuroectodermal tumor is a rare tumor of soft tissues of thoraco-pulmonary regions, pelvis and lower extremities. Involvement of visceral organs by primitive neuroectodermal tumor is even rarer, with the kidney being the most commonly involved organ. Involvement of the liver has been reported in the form of metastasis from other primary sources presenting as liver abscess. We report a 20-year-old lady presenting with massive hepatomegaly, with computed tomography scan evidence of diffuse hepatomegaly and a normal porta and intrahepatic biliary radicles. She subsequently underwent ultrasonography-guided true-cut needle biopsy of the liver. Histopathology of the liver revealed nests of small round blue tumor cells in the background of hepatocytes infiltrating the liver, which expressed Mic-2 and Fli-1, and were negative for cytokeratin, desmin, hepatocyte-specific antigen (OCHIE5), synaptophysin, chromogranin A and CD-20. Immunohistochemistry revealed CD-99-positive. Extensive search regarding any possible different site of involvement by the tumor was negative. The patient responded to a combination therapy of vincristine, adriamycin and cyclophosphamide alternating with ifosfamide and etoposide 3 weekly over 43 weeks and has been doing well even after 1 year of diagnosis. The clinical presentation, the macroscopic aspect, together with the histological pattern, the cytological characteristic and the cellular immunophenotype lead to the diagnosis of primary primitive neuroectodermal tumor of the liver which responded well to combination chemotherapy.

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

    Science.gov (United States)

    Dutta, Deep; Shivaprasad, K S; Das, Ram Narayan; Ghosh, Sujoy; Chowdhury, Subhankar

    2013-01-01

    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. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Byhardt, R.W.; Cox, J.D.; Holoye, P.Y.; Libnoch, J.A.

    1982-08-01

    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.

  14. Synthesis, spectroscopic, anticancer, antibacterial and antifungal studies of Ni(II) and Cu(II) complexes with hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene

    Science.gov (United States)

    Chandra, Sulekh; Vandana; Kumar, Suresh

    2015-01-01

    Schiff's base ligand(L) hydrazine carboxamide, 2-[3-methyl-2-thienyl methylene] and its metal complexes have been synthesized and characterized by elemental analysis, molar conductance, various spectroscopic techniques such as electronic, IR, 1H NMR, mass, EPR. Molar conductance of complexes in DMF solution corresponds to non-electrolyte. Complexes have general composition [M(L)2X2], where M = Ni(II) and Cu(II), X = Cl-, NO3-, CH3COO- and ½SO42-. On the basis of above spectral studies, an octahedral geometry has been assigned for Ni(II) complexes and tetragonal geometry for Cu(II) complexes except [Cu(L)2SO4] which possesses five coordinated trigonal bipyramidal geometry. These metal complexes were also tested for their anticancer, antibacterial and antifungal activities to assess their inhibition potential. Anticancer activity of ligand and its metal complexes were evaluated using SRB fluorometric assay and Adriamycin (ADR) was applied as positive control. Schiff's base ligand and its metal complexes were screened for their antibacterial and antifungal activity against Escherichia coli, Bacillus cereus and Aspergillus niger, Aspergillus flavus, respectively. Kirby-Bauer single disk susceptibility test was used for antibacterial activity and well diffusion method for antifungal activity of the compounds on the used fungi.

  15. 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.

  16. 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.

  17. 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.

  18. Sequential-release of anticancer drugs microcapsulated with ethylcellulose

    Institute of Scientific and Technical Information of China (English)

    顾耕华; 黄剑奇; 何虹

    2002-01-01

    Objective To approach the sequential release of antitumor drugs and promote the effect of chemotherapy.Methods Adriamycin (ADM) and carboplatin (CBP) were respectively microcapsulated with ethylcellulose by organic phase separation. The morphology and sizes of the microcapsules were observed and measured with light microscope and scanning electromicroscope. The contents and the release rates of ADM and CBP in microcapsules were measured with fluorescence spectrophotometer and high-efficiency phantom chromatic (HPC) spectrum respectively. The antitumor sensitivity test in vitro was devised with MTT assay.Results The microcapsules of ADM and CBP were spherical in shape with diameters of 196?4 μm and 214?8 μm respectively. The contents of one-layer and two-layer CBP and ADM microcapsules were 51.4%, 35.7% and 39.8% respectively, with the release rates in vitro of 62.4%/day, 54.8%/day and 48.2% /8h. The results of drug sensitivity test in vitro demonstrated that the current preparation has never affected the stability and antitumor activity of CBP and ADM.Conclusion Microcapsules with different drugs and different thickness of material have different release rate. Combined arterial chemoembolization with different microcapsules could approach the sequential release and promote the effect of chemotherapy.

  19. Effect of gemcitabine chemotherapy on immune function and VEGF in patients with middle and advanced liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ling Zuo; Yan Meng

    2016-01-01

    Objective:To observe the effect of gemcitabine chemotherapy on the immune function and VEGF in patients with middle and advanced liver cancer.Methods: A total of 90 patients with middle and advanced liver cancer who were admitted in our hospital from June, 2014 to July, 2015 were included in the study and randomized into the observation group and the control group with 45 cases in each group. The patients in the control group were given adriamycin, and the patients in the observation group were given gemcitabine chemotherapy. The efficacy, immunological function indicators, VEGF level, and the occurrence of adverse reactions in the two groups were compared.Results: IL-6 and TNF-α levels after treatment in the two groups were significantly elevated, and the increased degree in the observation group was significantly greater than that in the control group (P0.05). VEGF level after treatment in the two groups was significantly reduced, and the reduced degree in the observation group was significantly greater than that in the control group (P<0.05). The improvement of T cell subsets after treatment in the observation group was significantly superior to that in the control group (P<0.05). The occurrence rate of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05).Conclusions:Gemcitabine chemotherapy on patients with middle and advanced liver cancer can effectively improve the immunological function, and enhance the efficacy, with a higher safety.

  20. 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.

  1. Effect of mitomycin C on the activation of adenylate cyclase in rat ascites hepatoma AH130 cells.

    Science.gov (United States)

    Miyamoto, K; Matsunaga, T; Sanae, F; Koshiura, R

    1986-09-01

    Isoproterenol (IPN)-stimulated activity of adenylate cyclase was enhanced in a dose-dependent manner by exposure of AH130 cells to mitomycin C (MMC). The enhancement was also observed in prostaglandin E1-, guanine nucleotide analog-, NaF-, cholera toxin- and forskolin-stimulated activities of the enzyme but not in manganese-stimulated activity. In addition, even when the cells pretreated with islet-activating protein were exposed to MMC, IPN-stimulated activity of adenylate cyclase was enhanced. Anaerobic exposure of AH130 cells to MMC somewhat inhibited IPN-stimulated activity of adenylate cyclase in contrast with aerobic exposure. Exposure of cells to adriamycin also caused enhancement of IPN-stimulated activity of adenylate cyclase but exposure to nitrogen mustard inhibited the enzyme stimulation by IPN. The enhancing effect of MMC was lost by the combined treatment with alpha-tocopherol. From these results, it was shown that MMC modulated the activity of adenylate cyclase, probably through alterations in membrane structure.

  2. Temozolomide competes for P-glycoprotein and contributes to chemoresistance in glioblastoma cells.

    Science.gov (United States)

    Munoz, Jessian L; Walker, Nykia D; Scotto, Kathleen W; Rameshwar, Pranela

    2015-10-10

    Chemotherapeutic resistance can occur by P-glycoprotein (P-gp), a 12-transmembrane ATP-dependent drug efflux pump. Glioblastoma (GBM) has poor survival rate and uniformly acquired chemoresistance to its frontline agent, Temozolomide (TMZ). Despite much effort, overcoming TMZ resistance remains a challenge. We reported on autonomous induction of TMZ resistance by increased transcription MDR1, the gene for P-gp. This study investigated how P-gp and TMZ interact to gain resistance. Using an experimental model of Adriamycin-resistant DC3F cells (DC3F/Adx), we showed that increased P-gp caused TMZ resistance. Increasing concentrations of TMZ competed with Calcein for P-gp, resulting in reduced efflux in the DC3F/Adx cells. Three different inhibitors of P-gp reversed the resistance to TMZ in two different GBM cell lines, by increasing active Caspase 3. Molecular modeling predicted the binding sites to be the intracellular region of P-gp and also identified specific amino acids and kinetics of energy for the efflux of TMZ. Taken together, we confirmed P-gp targeting of TMZ, a crucial regulator of TMZ resistance in GBM. This study provides insights on the effectiveness by which TMZ competes with other P-gp substrates, thereby opening the door for combined targeted therapies.

  3. Management and prognosis of multiple myeloma.

    Science.gov (United States)

    Kyle, R A; Elveback, L R

    1976-12-01

    Patients with asymptomatic or smoldering multiple myeloma should not be treated but should be observed closely for progression. For symptomatic myeloma, chemotherapy is indicated. Melphalan, the agent of choice, should be given with prednisone for 1 week of every 6 weeks, If melphalan brings no response, or response and then relapse, cyclophosphamide (Cytoxan) should be give intravenously every 4 weeks or orally every day. BCNU, CCNU, and doxorubicin (Adriamycin) have also shown activity in myeloma. Hypercalcemia occurs in one-third of patients and should be countered with hydration, corticosteroids, Neutra-Phos, or mithramycin. Long-term hemodialysis has achieved some success. The combination of sodium flouride and calcium carbonate produces new bone formation; it seems a useful adjunct in treatment for myelomatous bone disease. Radiation should be utilized only for severe, localized pain or for solitary lesions. Survival with multiple myeloma varies, mean durations being 2 to 3 years. Multivariate analysis indicates that serum creatinine and calcium levels are the most significant indicators regarding 2-year survival. We have found monoclonal proteinuria not significantly more frequent with renal insufficiency than with normal renal function, renal insufficiency not significantly more frequent with lambda than with kappa chains, and survival not significantly greater with IgG myeloma than with IgA.

  4. Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin.

    Science.gov (United States)

    Kuhlmann, J; Zilly, W; Wilke, J

    1981-10-01

    Mucosal defects decrease digoxin absorption in patients with malabsorption syndromes. Since the intestinal mucosa can be damaged by cytostatic drugs, we investigated their effects on digoxin plasma levels and urinary digoxin excretion. In six patients with malignant lymphoma who received 0.8 mg beta-acetyldigoxin before and 24 hr after treatment with a combination of cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, oncovin, and prednisone (COP), plasma digoxin concentrations were measured 0 to 8 hr after the dose and areas under the plasma concentration-time curves were calculated. In 15 patients on 0.3 mg of beta-acetyldigoxin daily, plasma glycoside concentrations and renal excretion were measured daily before and after COPP, COP, cyclophosphamide, oncovin, cytosine-arabinosine, and prednisone (COAP), or adriamycin, bleomycin, and prednisone (ABP) treatment schemes. The diminished steady-state glycoside plasma concentrations and daily renal glycoside excretion during the 24 to 168 hr after the cytostatic drug established reversible impairment of digoxin absorption. The delayed time to peak after a single dose of digoxin during cytostatic drug therapy shows that extent and rate of digoxin absorption are reduced. To maintain adequate control of digoxin therapy in patients treated with cytostatic drugs, plasma levels should be monitored.

  5. Aggressive lymphoma in the elderly.

    Science.gov (United States)

    Lichtman, S M

    2000-02-01

    Persons 65 years of age and older are the fastest growing segment of the United States population. Over the next 30 years they will comprise approximately 20% of the population. There will be a parallel rise in the number of patients with non-Hodgkin's lymphoma. Age has long been known to be an adverse prognostic factor. Clinical trials of older patients are complicated by the effect of comorbid illness, particularly its effect on overall survival. CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) remains the standard therapy for all patients with aggressive non-Hodgkin's lymphoma. There are a number of regimens which may be beneficial for older patients with significant comorbidity and poor performance status. The randomized trials in the elderly has reaffirmed CHOP and emphasize the need for adequate dosing, maintaining schedule and anthracyclines. Relapsed patients have a poor prognosis but selected fit older patients may benefit from aggressive reinduction regimens and possibly bone marrow transplantation. Future research should include defining the role of comorbidity, measurement of organ dysfunction and assessment of performance status with geriatric functional scales. New drug treatments should also be explored.

  6. Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

    Science.gov (United States)

    Situ, Jun-Qing; Wang, Xiao-Juan; Zhu, Xiu-Liang; Xu, Xiao-Ling; Kang, Xu-Qi; Hu, Jing-Bo; Lu, Chen-Ying; Ying, Xiao-Ying; Yu, Ri-Sheng; You, Jian; Du, Yong-Zhong

    2016-10-01

    Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL-1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.

  7. 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.

  8. Noxa induces apoptosis in oncogene-expressing cells through catch-and-release mechanism operating between Puma and Mcl-1.

    Science.gov (United States)

    Nakajima, Wataru; Tanaka, Nobuyuki

    2011-10-07

    Tumor suppressor p53 induces apoptosis by transcriptional induction of Noxa and Puma, which encode the proapoptotic BH3-only member of the Bcl-2 family proteins. In the p53-mediated tumor surveillance system, p53 induces apoptosis or replicative senescence in oncogene-expressing cells, resulting in elimination of such cells. In this context, we previously found that Noxa and Puma synergistically induce apoptosis. Here, we found the adenovirus oncogene E1A to induce p53-dependently expression of Puma, but not Noxa. The induced Puma associates with antiapoptotic Bcl-2 protein Mcl-1, accompanied by accumulated Mcl-1 protein on mitochondria. Moreover, E1A also reduces expression of the antiapoptotic Bcl-2 protein Bcl-X(L). In contrast, the DNA-damaging agent adriamycin induces Noxa expression in E1A-expressing cells. Interestingly, Mcl-1 knockdown itself induced apoptosis in E1A-expressing MEFs. Furthermore, Noxa displaced Puma's association with Mcl-1, accompanied by Mcl-1 degradation and apoptosis induction by activating mitochondrial apoptotic executers Bax and Bak. These results suggest that p53-induced apoptosis in oncogene-expressing cells is regulated by differential induction and sequential activation of Noxa and Puma. Accumulated Puma by oncogene enhances susceptibility to apoptosis through "catch" in mitochondria by Mcl-1. Subsequently, in response to DNA-damage, Noxa efficiently induces apoptosis by "release" of Puma from Mcl-1.

  9. Establishment of multi-drug resistance human B-cell lymphoma cell line BJAB/ADR and preliminary research of its drug-resistance mechanism%人类B细胞淋巴瘤耐药细胞株BJAB/ADR的建立及其耐药机制的初步研究

    Institute of Scientific and Technical Information of China (English)

    鲍世琦; 姜琳琳; 张晓龙; 李真真; 邵晓枫; 齐怀丰; 杨雨琪; 熊冬生

    2014-01-01

    目的 建立人类淋巴瘤B JAB多药耐药细胞株BJAB/ADR,并初步研究其耐药机制.方法 采用多柔比星浓度梯度递增法建立人类B细胞淋巴瘤耐药细胞模型BJAB/ADR,观察其生长规律并绘制细胞生长曲线;用四甲基偶氮唑蓝(MTT)法鉴定耐药细胞株对多种化疗药物的耐药性并计算耐药指数;提取耐药细胞株RNA,实时定量聚合酶链反应(PCR)法检测相关耐药基因MDR1 mRNA的表达;流式细胞术检测细胞表面P糖蛋白(Pgp)的表达;通过罗丹明外排实验,检测Pgp功能.结果 成功建立B细胞淋巴瘤耐药细胞模型BJAB/ADR,并在160 ng/ml多柔比星溶液中稳定生长,耐药细胞较敏感细胞生长缓慢,细胞形态无明显变化.MTT检测结果表明BJAB/ADR细胞对多柔比星的耐药指数为43倍,同时对柔红霉素、依托泊苷、高三尖杉酯碱(HHT)及米托蒽醌(MX)也具有一定的耐药性.实时定量PCR结果表明,耐药细胞BJAB/ADR MDRl mRNA明显高于药物敏感细胞BJAB(P< 0.01).流式细胞术检测结果显示,耐药细胞表面Pgp高表达;罗丹明外排实验表明Pgp对多柔比星具有外排功能,使B JAB/ADR细胞获得耐药特性.结论 建立了人类B细胞淋巴瘤的耐药细胞株BJAB/ADR,其对多柔比星耐药性稳定,并呈现多药耐药细胞的基本生物学特性,为进一步研究肿瘤多药耐药发生的机制及逆转耐药提供有利的模型.%Objective To establish human multi-drug resistance (MDR) B-cell lymphoma cell line BJAB/ADR and investigate its biological characteristics.Methods Human B-cell lymphoma MDR cell line BJAB/ADR was induced by exposure to increasing dose of adriamycin.The growing features of BJAB/ADR were observed and cell growth was measured,IC50 of antitumor agents was evaluated by MTT assay.The expression of MDR1 mRNA was determined with real-time PCR,FACS was applied to study the expression of MDR protein P-glycoprotein (Pgp) and Rhodamine 123R efflux assay was used to

  10. CARP-1 / CCAR1: A biphasic regulator of cancer cell growth and apoptosis

    Science.gov (United States)

    Muthu, Magesh; Cheriyan, Vino T.; Rishi, Arun K.

    2015-01-01

    Targeted cancer therapy using small molecule inhibitors (SMIs) has been useful in targeting the tumor cells while sparing the normal cells. Despite clinical success of many targeted therapies, their off-target effects and development of resistance are emerging as significant and challenging problems. Thus, there is an urgent need to identify targets to devise new means to treat cancers and their drug-resistant phenotypes. CARP-1/CCAR1 (Cell division cycle and apoptosis regulator 1), a peri-nuclear phospho-protein, plays a dynamic role in regulating cell growth and apoptosis by serving as a co-activator of steroid/thyroid nuclear receptors, β-catenin, Anaphase Promoting Complex/Cyclosome (APC/C) E3 ligase, and tumor suppressor p53. CARP-1/CCAR1 also regulates chemotherapy-dependent apoptosis. CARP-1/CCAR1 functional mimetics (CFMs) are a novel SMIs of CARP-1/CCAR1 interaction with APC/C. CFMs promote apoptosis in a manner independent of p53. CFMs are potent inhibitors of a variety of cancer cells including the drug (Adriamycin or Tamoxifen)-resistant breast cancer cells but not the immortalized breast epithelial cells, while a nano-lipid formulation of the lead compound CFM-4 improves its bioavailability and efficacy in vivo when administered orally. This review focuses on the background and pleiotropic roles of CARP-1/CCAR1 as well as its apoptosis signaling mechanisms in response to chemotherapy in cancer cells. PMID:25894788

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Regulation of cell survival by Na+/H+ exchanger-1.

    Science.gov (United States)

    Schelling, Jeffrey R; Abu Jawdeh, Bassam G

    2008-09-01

    Na(+)/H(+) exchanger-1 (NHE1) is a ubiquitous plasma membrane Na(+)/H(+) exchanger typically associated with maintenance of intracellular volume and pH. In addition to the NHE1 role in electroneutral Na(+)/H(+) transport, in renal tubular epithelial cells in vitro the polybasic, juxtamembrane NHE1 cytosolic tail domain acts as a scaffold, by binding with ezrin/radixin/moesin (ERM) proteins and phosphatidylinositol 4,5-bisphosphate, which initiates formation of a signaling complex that culminates in Akt activation and opposition to initial apoptotic stress. With robust apoptotic stimuli renal tubular epithelial cell NHE1 is a caspase substrate, and proteolytic cleavage may permit progression to apoptotic cell death. In vivo, genetic or pharmacological NHE1 loss of function causes renal tubule epithelial cell apoptosis and renal dysfunction following streptozotocin-induced diabetes, ureteral obstruction, and adriamycin-induced podocyte toxicity. Taken together, substantial in vivo and in vitro data demonstrate that NHE1 regulates tubular epithelial cell survival. In contrast to connotations of NHE1 as an unimportant "housekeeping" protein, this review highlights that NHE1 activity is critical for countering tubular atrophy and chronic renal disease progression.

  14. 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.

  15. A case of Langerhans' cell histiocytosis following Hodgkin's disease

    Science.gov (United States)

    LI, XIN; DENG, QI; LI, YU-MING

    2016-01-01

    Langerhans' cell histiocytosis (LCH) is a group of disorders in various tissues characterized by the proliferation of Langerhans cells. It is rarely observed in adults. Langerhans cells are dendritic cells that express cluster of differentiation 1a (CD1a) and S100 protein, and contain Birbeck granules. Its etiopathogenesis remains to be elucidated. One possible etiological cause is a reactive proliferation of Langerhans cells following chemotherapy or radiotherapy for Hodgkin's disease (HD). A number of cases of LCH associated with malignant lymphoma have been reported previously. It may follow after the malignant lymphoma, or occur with it. However, fewer cases have been reported where the LCH followed after HD. In the present case report, a patient was diagnosed with HD following chemotherapy for LCH. As LCH was diagnosed, the patient was treated with a combination of various chemotherapeutic agents in two cycles of cyclophosphamide, vincristine, and prednisolone (COP), and eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The patient went into a successful clinical remission. One year later, computed tomographic (CT) scans of the thorax and abdomen revealed augmentation of the tumor mass in the mediastinum. An excisional biopsy of the right inguinal lymph node was performed. The patient was diagnosed with nodular sclerosing Hodgkin's disease. Following four cycles of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, a whole-body positron emission tomographic CT scan revealed a decrease in tumor mass in the mediastinum. At present, the patient remains in treatment, and the prognosis has yet to be fully determined. PMID:27330759

  16. Absolute neutrophil values in malignant patients on cytotoxic chemotherapy.

    Science.gov (United States)

    Madu, A J; Ibegbulam, O G; Ocheni, S; Madu, K A; Aguwa, E N

    2011-01-01

    A total of eighty patients with various malignancies seen between September 2008 and April 2009 at the University of Nigeria Teaching Hospital (UNTH) Ituku Ozalla, Enugu, Nigeria, had their absolute neutrophil counts, done at Days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed of various malignancies, consisting of Breast cancer 36 (45%), Non-Hodgkin's lymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%), Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1 (1.25%) and other malignancies 9 (11.25%), Manual counting of absolute neutrophil count was done using Turks solution and improved Neubauer counting chamber and Galen 2000 Olympus microscope. The socio demographic data of the patients were assessed from a questionnaire. There were 27 males (33.75%) and 53 females (66.25%). Their ages ranged from 18 - 80 years with a median of 45 years. The mean absolute neutrophil count of the respondents pre-and post chemotherapy was 3.7 +/- 2.1 x 10(9)/L and 2.5 +/- 1.6 x 10(9)/L respectively. There were significant differences in both the absolute neutrophil count (p=0.00) compared to the pre-chemotherapy values. Chemotherapeutic combinations containing cyclophosphamide and Adriamycin were observed to cause significant reduction in absolute neutrophil.

  17. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

    Science.gov (United States)

    Rotta, Marcello; Patriarca, Francesca; Mattei, Daniele; Allione, Bernardino; Carnevale-Schianca, Fabrizio; Sorasio, Roberto; Rambaldi, Alessandro; Casini, Marco; Parma, Matteo; Bavaro, Pasqua; Onida, Francesco; Busca, Alessandro; Castagna, Luca; Benedetti, Edoardo; Iori, Anna Paola; Giaccone, Luisa; Palumbo, Antonio; Corradini, Paolo; Fanin, Renato; Maloney, David; Storb, Rainer; Baldi, Ileana; Ricardi, Umberto; Boccadoro, Mario

    2009-01-01

    Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)–based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m2) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)–identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of “new drugs” in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.) PMID:19064724

  18. 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.

  19. Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

    Science.gov (United States)

    Huang, Ning; Zhong, Yueling; Zeng, Ting; Wei, Rong; Wu, Zhongjun; Xiao, Cui; Cao, Xiaohua; Li, Minhui; Li, Limei; Han, Bin; Yu, Xiaoping; Li, Hua; Zou, Qiang

    2017-01-01

    Cucurbitacin B (CuB), a triterpenoid compound isolated from the stems of Cucumis melo, has long been used to treat hepatitis and hepatoma in China. Although its remarkable anti-cancer activities have been reported, the mechanism by which it achieves this therapeutic activity remains unclear. This study was designed to investigate the molecular mechanisms by which CuB inhibits cancer cell proliferation. Our results indicate that CuB is a novel inhibitor of Aurora A in multiple myeloma (MM) cells, arresting cells in the G2/M phase. CuB also inhibited IL-10-induced STAT3 phosphorylation, synergistically increasing the anti-tumor activity of Adriamycin in vitro. CuB induced dephosphorylation of cofilin, resulting in the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-8. CuB inhibited MM tumor growth in a murine MM model, without host toxicity. In conclusion, these results indicate that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. PMID:27418139

  20. 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

    2016-07-20

    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.

  1. Rack1 Mediates the Interaction of P-Glycoprotein with Anxa2 and Regulates Migration and Invasion of Multidrug-Resistant Breast Cancer Cells

    Science.gov (United States)

    Yang, Yi; Wu, Na; Wang, Zhiyong; Zhang, Fei; Tian, Ran; Ji, Wei; Ren, Xiubao; Niu, Ruifang

    2016-01-01

    The emergence of multidrug resistance is always associated with more rapid tumor recurrence and metastasis. P-glycoprotein (P-gp), which is a well-known multidrug-efflux transporter, confers enhanced invasion ability in drug-resistant cells. Previous studies have shown that P-gp probably exerts its tumor-promoting function via protein-protein interaction. These interactions were implicated in the activation of intracellular signal transduction. We previously showed that P-gp binds to Anxa2 and promotes the invasiveness of multidrug-resistant (MDR) breast cancer cells through regulation of Anxa2 phosphorylation. However, the accurate mechanism remains unclear. In the present study, a co-immunoprecipitation coupled with liquid chromatography tandem mass spectrometry-based interactomic approach was performed to screen P-gp binding proteins. We identified Rack1 as a novel P-gp binding protein. Knockdown of Rack1 significantly inhibited proliferation and invasion of MDR cancer cells. Mechanistic studies demonstrated that Rack1 functioned as a scaffold protein that mediated the binding of P-gp to Anxa2 and Src. We showed that Rack1 regulated P-gp activity, which was necessary for adriamycin-induced P-gp-mediated phosphorylation of Anxa2 and Erk1/2. Overall, the findings in this study augment novel insights to the understanding of the mechanism employed by P-gp for promoting migration and invasion of MDR cancer cells. PMID:27754360

  2. Effects of antineoplastic agents and ionizing irradiation on a human testicular cancer xenograft

    Energy Technology Data Exchange (ETDEWEB)

    Osieka, R.; Pfeiffer, R.; Glatte, P.; Schmidt, C.G.; Bamberg, M.; Scherer, E.

    1985-01-01

    Chemotherapy has afforded a high percentage of definitive cures in advanced testicular cancer. Nevertheless some patients with large tumor burden still succumb to chemorefractory disease. Therefore preclinical and clinical evaluation of new drugs and agents not primarily used against this type of disease are still mandatory. For preclinical drug screening purposes heterotransplantation of specific human tumors yields a model with high validity for tumor markers and drug response. Heterotransplantation of a human embryonal testicular cancer was used for simultaneous testing of established agents such as cisplatin, melphalan, bleomycin, vinblastine, etoposide and adriamycin and some newer derivatives such as PHM or mafosfamide. Furthermore agents such as procarbazine, dacarbazine and methyl-CCNU that cross the blood-brain-barrier displayed some interesting activity. The results hint at a unique chemosensitivity pattern of the xenograft line, with some accordance between clinical response to vinblastine and bleomycin and good response of the xenografts to bleomycin but not to vinblastine. Radiotherapy was also effective against this tumor line, but there was not much difference in response when the schedule of fractionation was changed. It is concluded that a combined modality approach might salvage patients with residual, chemorefractory disease.

  3. 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.)

  4. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bajetta, E.; Valagussa, P.; Bonadonna, G.; Lattuada, A.; Buzzoni, R.; Rilke, F.; Banfi, A.

    1988-07-01

    This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.

  5. 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.

  6. Radiation therapy for unresected gastric lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kataoka, Masaaki; Kawamura, Masashi; Kimura, Yoshiko; Itoh, Hisao; Tsuda, Takaharu; Komatsu, Akira; Hamamoto, Ken (Ehime Univ., Ehime (Japan). School of Medicine)

    1990-05-01

    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).

  7. Chemotherapy combined with involved-field radiotherapy for 177 children with Hodgkin's disease treated in 1983-1987

    Energy Technology Data Exchange (ETDEWEB)

    Balwierz, W.; Armata, J.; Moryl-Bujakowska, A. (Nicolaus Copernicus Univ., Cracow (Poland). School of Medicine) (and others)

    1991-12-01

    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.).

  8. 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.

  9. MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway

    Science.gov (United States)

    Miao, Yuan; Zheng, Wei; Li, Nana; Su, Zhen; Zhao, Lifen; Zhou, Huimin; Jia, Li

    2017-01-01

    Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among breast cancer patients. This study was aimed to investigate the possible mechanism by which microRNA-130b-3p (miR-130b) mediates the chemoresistance and proliferation of breast cancer. MiR-130b was found to be up-regulated in tumor tissues versus adjacent tissues of breast cancer, as well as in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) versus its parental line (MCF-7) and the non-malignant breast epithelial cell line (MCF-10A), demonstrating its crucial relevance for breast cancer biology. We identified that PTEN was a direct target of miR-130b and inversely correlated with miR-130b expression in breast cancer. Moreover, over-expression of miR-130b promoted drug resistance, proliferation and decreased apoptosis of MCF-7 cells, while suppression of miR-130b enhanced drug cytotoxicity and apoptosis, as well as reduced proliferation of MCF-7/ADR cells in vitro and in vivo. Particularly, miR-130b mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway as well as the chemoresistance and proliferation of breast cancer cell lines, which was partially blocked following knockdown of PTEN. Altogether, miR-130b targets PTEN to induce MDR, proliferation, and apoptosis via PI3K/Akt signaling pathway. This provides a novel promising candidate for breast cancer therapy. PMID:28165066

  10. Splenic irradiation-induced gastric variceal bleeding in a primary splenic diffuse large B-cell lymphoma patient: a rare complication successfully treated by splenectomy with short gastric vein ligation

    Directory of Open Access Journals (Sweden)

    Lin Ying-Chu

    2012-07-01

    Full Text Available Abstract Primary splenic diffuse large B-cell lymphoma (DLBCL is a rare clinical condition, which is generally treated by six to eight cycles of chemotherapy involving a combination of rituximab and the cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP regimen. However, the treatment for chemorefractory primary splenic DLBCL remains controversial. Therapeutic splenic irradiation (SI might be a reasonable and possibly the only treatment option with curative intention for patients with chemorefractory primary splenic DLBCL. However, the efficacy and safety of therapeutic SI are unclear. Herein, we present the case of a primary splenic DLBCL patient who was refractory to multiple chemotherapy regimens but achieved complete remission after administration of therapeutic SI. However, his condition was complicated with severe gastric variceal bleeding due to splenic venous thrombosis, which was successfully treated via splenectomy and short gastric vein ligation. On the basis of our findings, we concluded that the splenic venous thrombosis-induced gastric variceal bleeding was a rare but life-threatening adverse effect of the therapeutic SI administered for primary splenic DLBCL. Surgical intervention involving splenectomy and short gastric vein ligation is mandatory and should be performed as soon as possible for such patients.

  11. 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.

  12. 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.

  13. Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase {pi} gene

    Energy Technology Data Exchange (ETDEWEB)

    Miyara, Hajime; Nishida, Keiko; Takahashi, Toshitada; Takahashi, Takashi; Ueda, Ryuzo [Aichi Cancer Center, Nagoya (Japan). Research Inst.; Hida, Toyoaki; Sugiura, Takahiko; Ariyoshi, Yutaka; Morishita, Munehiko

    1996-02-01

    Recent studies have suggested that glutathione S-transferase {pi} (GST-{pi}) 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-{pi} 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-{pi} 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-{pi} 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. Demodex spp. Infestation in a breast-cancer patient: A case report.

    Science.gov (United States)

    Olt, Serdar; Yalçın, Gülter Gülter; Uysal, Ozlem Sönmez; Karakeçe, Engin; Ciftci, Ihsan Hakkı

    2013-09-01

    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/cm(2) on her right and left cheeks, and 15 mites/cm(2) 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/cm(2) on her right and left cheeks and 30 mites/cm(2) on her forehead, which were nearly 2.5-times higher than the previous examination. This increase probably was associated with immune suppression of chemotherapy.

  15. 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.

  16. 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

    Energy Technology Data Exchange (ETDEWEB)

    Fromm, M.; Littman, P.; Raney, R.B.; Nelson, L.; Handler, S.; Diamond, G.; Stanley, C.

    1986-05-15

    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.

  17. Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance.

    Science.gov (United States)

    Yhee, Ji Young; Song, Seungyong; Lee, So Jin; Park, Sung-Gurl; Kim, Ki-Suk; Kim, Myung Goo; Son, Sejin; Koo, Heebeom; Kwon, Ick Chan; Jeong, Ji Hoon; Jeong, Seo Young; Kim, Sun Hwa; Kim, Kwangmeyung

    2015-01-28

    P-glycoprotein (Pgp) mediated multi-drug resistance (MDR) is a major cause of failure in chemotherapy. In this study, small interfering RNA (siRNA) for Pgp down-regulation was delivered to tumors to overcome MDR in cancer. To achieve an efficient siRNA delivery in vivo, self-polymerized 5'-end thiol-modified siRNA (poly-siRNA) was incorporated in tumor targeting glycol chitosan nanoparticles. Pgp-targeted poly-siRNA (psi-Pgp) and thiolated glycol chitosan polymers (tGC) formed stable nanoparticles (psi-Pgp-tGC NPs), and the resulting nanoparticles protected siRNA molecules from enzymatic degradation. The psi-Pgp-tGC NPs could release functional siRNA molecules after cellular delivery, and they were able to facilitate siRNA delivery to Adriamycin-resistant breast cancer cells (MCF-7/ADR). After intravenous administration, the psi-Pgp-tGC NPs accumulated in MCF-7/ADR tumors and down-regulated P-gp expression to sensitize cancer cells. Consequently, chemo-siRNA combination therapy significantly inhibited tumor growth without systemic toxicity. These psi-Pgp-tGC NPs showed great potential as a supplementary therapeutic agent for drug-resistant cancer.

  18. Glycogen synthase kinase 3β dictates podocyte motility and focal adhesion turnover by modulating paxillin activity: implications for the protective effect of low-dose lithium in podocytopathy.

    Science.gov (United States)

    Xu, Weiwei; Ge, Yan; Liu, Zhihong; Gong, Rujun

    2014-10-01

    Aberrant focal adhesion turnover is centrally involved in podocyte actin cytoskeleton disorganization and foot process effacement. The structural and dynamic integrity of focal adhesions is orchestrated by multiple cell signaling molecules, including glycogen synthase kinase 3β (GSK3β), a multitasking kinase lately identified as a mediator of kidney injury. However, the role of GSK3β in podocytopathy remains obscure. In doxorubicin (Adriamycin)-injured podocytes, lithium, a GSK3β inhibitor and neuroprotective mood stabilizer, obliterated the accelerated focal adhesion turnover, rectified podocyte hypermotility, and restored actin cytoskeleton integrity. Mechanistically, lithium counteracted the doxorubicin-elicited GSK3β overactivity and the hyperphosphorylation and overactivation of paxillin, a focal adhesion-associated adaptor protein. Moreover, forced expression of a dominant negative kinase dead mutant of GSK3β highly mimicked, whereas ectopic expression of a constitutively active GSK3β mutant abolished, the effect of lithium in doxorubicin-injured podocytes, suggesting that the effect of lithium is mediated, at least in part, through inhibition of GSK3β. Furthermore, paxillin interacted with GSK3β and served as its substrate. In mice with doxorubicin nephropathy, a single low dose of lithium ameliorated proteinuria and glomerulosclerosis. Consistently, lithium therapy abrogated GSK3β overactivity, blunted paxillin hyperphosphorylation, and reinstated actin cytoskeleton integrity in glomeruli associated with an early attenuation of podocyte foot process effacement. Thus, GSK3β-modulated focal adhesion dynamics might serve as a novel therapeutic target for podocytopathy.

  19. Recombinant human thrombopoietin in myelosuppressive chemotherapy.

    Science.gov (United States)

    Vadhan-Raj, S

    2001-07-01

    Recombinant human thrombopoietin (rhTPO) is a full-length glycosylated molecule that has been under evaluation in the setting of chemotherapy-induced myelosuppression. It has been shown to be a potent stimulator of platelet production in cancer patients when administered prior to chemotherapy. The peak platelet response to a single dose of rhTPO is observed around day 12, and is accompanied by a significant increase in the number of mature megakaryocytes in bone marrow. Consistent with this biologic effect, rhTPO administered postchemotherapy has been shown to be effective in attenuating severe thrombocytopenia induced by carboplatin, which produces a late platelet nadir. Early clinical experience with a regimen that produces an early nadir, however, such as AI (doxorubicin [Adriamycin] and ifosfamide [Ifex]), suggests that administration of rhTPO both prior to and following chemotherapy might be important to reduce thrombocytopenia severity. Treatment with rhTPO in these clinical trials has been well tolerated with a favorable safety profile. Randomized clinical trials have been initiated to determine further the importance of schedule in the prevention and treatment of severe thrombocytopenia in cancer patients.

  20. In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity

    Directory of Open Access Journals (Sweden)

    A. G. Nerkar

    2009-01-01

    Full Text Available Dihydrofolate reductase (DHFR is the important target for anticancer drugs belonging to the class of antimetabolites as the enzyme plays important role in the de novo purine synthesis. We here report the in silico screening to obtain best fit molecules as DHFR inhibitors, synthesis of some ʻbest fitʼ quinazolinone from 2-phenyl-3-(substituted-benzilidine-amino quinazolinones (Quinazolinone Shiff's bases QSB1-5 and pyridine-4-carbohydrazide Shiff's bases (ISB1-5 derivatives and their in vitro anticancer assay. Synthesis of the molecules was performed using microwave assisted synthesis. The structures of these molecules were elucidated by IR and 1H-NMR. These compounds were then subjected for in vitro anticancer evaluation against five human cancer cell-lines for anticancer cyto-toxicity assay. Methotrexate (MTX was used as standard for this evaluation to give a comparable inhibition of the cell proliferation by DHFR inhibition. Placlitaxel, adriamycin and 5-fluoro-uracil were also used as standard to give a comparable activity of these compounds with other mechanism of anticancer activity. ISB3 (4-(N, N-dimethyl-amino-phenyl Schiff''s base derivative of pyridine carbohydrazide showed equipotent activity with the standards used in in vitro anticancer assay as per the NCI (National Cancer Institute guidelines.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Five year retrospective survival analysis of triple negative breast cancer in North-West India

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    B Sharma

    2013-01-01

    Full Text Available Background: In our institute, about 10% of total cancer is female breast cancer. This analysis was performed to check triple negativity among these patients with their survival strength up to 5 years in relation to different age groups, stage and chemotherapy protocols. Materials and Methods: 208 immunohistochemistry proved triple negative breast cancer patients registered and treated until 2008 were retrospectively selected for the study. Overall survival up to 5 years was observed on the basis of stage, different age groups and chemotherapy regimens. All patients had undergone surgery, conventional external beam radiation therapy and adjuvant chemotherapy. The survival analyses were performed using the Kaplan-Meier method. Results: The majority of patients (41% were in the age group 21-30 years. Stage IV was seen in 18% of the patients at diagnosis and mainly in 21-40 years age group. Only 3% of females were >70 years age and were of Stage I and II. Overall 5 year survival in Stage I in Cyclophosphamide, Adriamycin/Epirubicin, 5-Flurouracil group was 37.5% as compared with Docetaxel/Paclitaxel, Epirubicin group 93% (P < 0.0001. Conclusion: Triple negativity in North-West India is about 11.8%. We observed it in younger patients mainly with highly aggressive behaviors. Taxane based chemotherapy gives better result as compared with anthracycline based regimens in all stages.

  3. 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

  4. Mecobalamin promotes mouse sperm maturation.

    Science.gov (United States)

    Oshio, S; Ozaki, S; Ohkawa, I; Tajima, T; Kaneko, S; Mohri, H

    1989-01-01

    The effect of Mecobalamin (alpha-(5,6-dimethyl benzimidazolyl)-Co-methyl-cobamide: Me-B 12) on sperm production in the oligozoospermic mice experimentally induced by the treatment with adriamycin (0.3 mg/kg, three times a week for 5 weeks) was evaluated quantitatively by means of equilibrium sedimentation in Percoll. After centrifugation, the distribution profile of the sperm showed two peaks, i.e. the first peak near the bottom consisting of mature sperm with good motility and the second peak containing immature and/or immotile sperm. By oral administration of Me B 12 (1.0 mg/kg/day) to the oligozoospermic mice for 10 weeks, the sperm count, sperm motility, motile sperm count, diameter of seminiferous tubules and the percentage of good motile sperm with higher apparent density were increased as compared with those of the control. These results suggest that Me-B 12 enhanced the testicular function, resulting in an increased output of mature sperm.

  5. Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

    Science.gov (United States)

    Situ, Jun-Qing; Wang, Xiao-Juan; Zhu, Xiu-Liang; Xu, Xiao-Ling; Kang, Xu-Qi; Hu, Jing-Bo; Lu, Chen-Ying; Ying, Xiao-Ying; Yu, Ri-Sheng; You, Jian; Du, Yong-Zhong

    2016-01-01

    Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL−1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection. PMID:27775017

  6. Angiopoietin-like protein 3 modulates barrier properties of human glomerular endothelial cells through a possible signaling pathway involving phosphatidylinositol-3 kinase/protein kinase B and integrin α V β 3

    Institute of Scientific and Technical Information of China (English)

    Yunling Li; Li Sun; Hong Xu; Zhengyu Fang; Wantong Yao; Wei Guo; Jia Rao; Xiliang Zha

    2008-01-01

    Podocytes can influence glomerular endothelial cell (GEnC) barrier properties and take part in the development of proteinuria by some molecules. Angiopoietin-like protein 3 (Angptl3), secreted by podocytes, is a member of the angiopoietin-like protein family that has important biological functions in endothelial cells. In our previous studies, we showed that mRNA expression of Angptl3 increased significantly in kidneys of children with minimal change nephrotic syndrome. And the mRNA level of Angptl3 was increased in the glomerulus of adriamycin rats with the development of proteinuria. It was also found that Angptl3 was expressed in the cytoplasm of cultured podocytes. Thus, Angptl3 might influence the biological functions of GEnCs in a paracrine manner. In this study, we found that Angptl3 could increase the permeability of GEnCs and increase the level of protein kinase B phosphorylation in cultured GEnCs in vitro. LY294002, a phosphatidylinositol-3 kinase inhibitor, could prevent the increase of permeability of GEnCs induced by Angptl3. Our results also indicated that the integrin α V β 3 antibody (LM609) could block the Angptl3-induced protein kinase B phosphorylation.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

  9. Malignant histiocytosis: a clinicopathologic study of 18 consecutive cases.

    Science.gov (United States)

    Rilke, F; Carbone, A; Musumeci, R; Pilotti, S; De Lena, M; Bonadonna, G

    1978-04-30

    The clinical records and histologic material of 18 consecutive patients with malignant histiocytosis were reviewed. The age of the patients ranged from 20 months to 72 years (median 35 years). There were 14 males and 4 females (3.5:1). Lymph node and liver enlargement, fever, and skin nodules were the most common physical findings; and leukocytosis was frequently the most abnormal laboratory test. Seven of 18 patients died, and their survival ranged from 1 to 15 months (median 8 months) after histopathologic diagnosis. The histologic findings on lymph nodes, spleen, liver, bone marrow, and skin were investigated with special reference to both the cellular composition and the pattern of lymph node involvement. Vascular invasion of small perinodal vessels was observed in 4 fatal cases. The absence of capsular invasion and the lack of cohesiveness among atypical proliferating histiocytes of malignant histiocytosis appeared to be inconstant. Sequential lymph node biopsies revealed in later stages the extension of the histiocytic proliferation from the sinuses into the cords and the complete obliteration of the nodal structures. The radiologic investigations yielded numerous pathologic findings that were consistent with the dissemination of the disease. Complete response to initial treatment was achieved in patients that were treated with radiotherapy and/or chemotherapy. Complete response with chemotherapy was achieved only when the treatment included adriamycin. The histologic and clinical features of the present series provide future evidence for the recognition of malignant histiocytosis as a distinct clinical and pathologic entity.

  10. Axillary Metaplastic Breast Carcinoma with Ipsilateral Pectoral Invasive Ductal Carcinoma: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2014-01-01

    Full Text Available We report a case of axillary metaplastic breast carcinoma (MBC with triple negative (ER−/PR−/Her2− phenotype, concurrent with multifocal invasive ductal carcinoma (IDC of ipsilateral pectoral breast (ER+/PR+/Her2− in a 60-year-old woman. The two tumors demonstrate different morphology, immunophenotype, and opposite response to neoadjuvant chemotherapy of paclitaxol, adriamycin, and cyclophosphamide. Methylation analysis of human androgen receptor (HUMARA on X-chromosome identified monoclonal pattern of X-chromosome inactivation in MBC and mosaic pattern in the IDC. Stem cell origin of MBC is suggested in this case. Clinicopathological features, imaging findings, biological markers, chemoradiation management, and prognosis of MBC are reviewed in comparison to invasive ductal carcinoma. Our case and literature review suggest that traditional chemotherapy applicable to IDC is less effective towards MBC. However, new chemotherapy protocols targeting stem cell and multimodality management of MBC are promising. Recognition of unusual presentation of MBC will help tailor therapy towards tumor with worse prognosis.

  11. 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.

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

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    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.

  13. Biochemical and genetic analysis of toxic effect of HOE 15030 in mammalian cells.

    Science.gov (United States)

    Ishida, R; Nishizawa, M; Kohtani, F; Takahashi, T

    1989-07-01

    HOE 15030 inhibited the growth of BHK cells at concentrations that did not inhibit their nuclear DNA and RNA syntheses. When BHK cells were cultured in the presence of 30 micrograms/ml of HOE 15030, cells were arrested in the G1 phase after one or two cell divisions. After removal of the drug, cells progressed through the G1 to the S phase. HOE 15030 inhibited the activities of both topoisomerases I and II in vitro. To determine the target molecule of HOE 15030 in cells, we isolated a HOE 15030-resistant (HOEr) mutant of BHK cells. The HOEr cells exhibited cross-resistance to ethidium bromide, acriflavine, and rhodamine 123, and slight cross-resistance to 4'-dimethylepipodophyllotoxin-4-(4,6-O-ethylidine-beta-D-glu copyranoside) (VP-16) and adriamycin, but not to chloramphenicol, oligomycin, novobiocin, colchicine, or vinblastine. The uptake and retention of rhodamine 123 by HOEr cells were lower than those by BHK cells. Mitochondrial DNA synthesis of HOEr cells was more resistant to HOE 15030 and ethidium bromide than that of wild-type cells. These results indicate that the resistance of HOEr cells to drugs is due to reduced uptake or accumulation of the drugs by mitochondria and suggest that the mitochondria are the main target of HOE 15030 in cells.

  14. In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model

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    Sun, Zhongchan; Song, Xinxing; Li, Xiujuan; Su, Tao; Qi, Shun; Qiao, Ruirui; Wang, Fu; Huan, Yi; Yang, Weidong; Wang, Jing; Nie, Yongzhan; Wu, Kaichun; Gao, Mingyuan; Cao, Feng

    2014-11-01

    miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADRfluc tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment.miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug

  15. Study on the Flavonoid of Huanglian Jiedu Decoction in Reversing MDR of K562/ADM%黄连解毒汤中黄酮成分逆转K562/ADM多药耐药的实验观察

    Institute of Scientific and Technical Information of China (English)

    盛国良; 林潇; 孙付军; 李贵海

    2012-01-01

    目的:观察黄连解毒汤中黄酮成分逆转肿瘤多药耐药的作用,探讨本方逆转肿瘤多药耐药的物质基础.方法:以人慢性粒细胞白血病红白血病细胞株K562的耐阿霉素(adriamycin,ADM)细胞株(K562/ADM)为细胞系,通过MTT实验观察黄芩苷、京尼平苷对K562/ADM细胞ADM的敏感性的影响,计算细胞增殖抑制率、半数抑制浓度(IC50)及耐药逆转倍数,并对细胞内ADM浓度变化进行测定.结果:黄芩苷、京尼平苷均能部分逆转K562/ADM细胞.黄芩苷、京尼平苷的IC50值分别为5.06,6.74 mg·L-1.黄芩苷、京尼平苷的耐药逆转倍数分别为1.95,1.46倍.与相应的对照组相比,K562/ADM细胞经黄芩苷(50 mg·L-1)、京尼平苷(100 mg·L-1)作用后,细胞内ADM的荧光强度高于对照组,其中黄芩苷组提高到3.6%,京尼平苷组提高到1.7%.结论:黄连解毒汤逆转肿瘤多药耐药的物质基础可能与其含有的黄芩苷、京尼平苷有关.%Objective; To observe the effect on the flavoniod of Huanglian Jiedu decoction, and discuss its material base in reversing multiple-drug resistance (MDR) of cancer so as to provide the theory basis for Huanglian Jiedu decoction in clinical practices. Method: MTT assay was adopted to test the sensitivity of baicalin and geniposide to adriamycin ( ADM ) of K562/ADM, the inhibitory rate was calculated, the value of 50% inhibition concentration (IC50) and the multiple of the reversal of drug resistance as well as the change of the concentration of the intracellular ADM were assayed by using ADM K562/ADM of human chronic myelogenous leukemia (CML) erythroleukemia K562 as cell line. Result; Both baicalin and geniposide could partly reverse K562/ADM cell. The value of IC50of baicalin and geniposide was 5. 06 mg - L~ and 6. 74 mg - L-1respectively. The multiple of the reversal of drug resistance of baicalin and geniposide was 1.95 times and 1.46 times. The fluorescence intensity of the intracellular K562/ADM was

  16. Median effective effect-site concentration of intravenous anesthetics for loss of consciousness in neoadjuvant chemotherapy patients

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    HE Zi-jing; HU Yong-hua; FAN Zhi-yi

    2011-01-01

    Background In recent years, increasing numbers of patients are accepting neoadjuvant chemotherapy before their operation in order to get a better prognosis. But chemotherapy has many side-effects. We have observed that patients who accepted neoadjuvant chemotherapy are more sensitive to anesthetics. The aim of this study was to determine the median effective dose (EC50) of intravenous anesthetics for neoadjuvant chemotherapy patients to lose consciousness during target-controlled infusion.Methods Two hundred and forty breast cancer patients undergoing elective operations were assigned to six groups according to treatment received before their operation and the use of intravenous anesthetics during anesthesia;non-adjuvant chemotherapy+propofol group (group NP, n=40), Taxol+propofol group (group TP, n=40),adriamycine+cyclophosphamide+5-Fu+propofol group (group CP, n=40), non-adjuvant chemotherapy+etomidate group (group NE, n=40), taxol+etomidate group (group TE, n=40), adriamycine+cyclophosphamide+5-Fu+etomidate group (group CE, n=40). We set the beginning effect-site concentration (Ce) of propofol as 3.0 μg/ml and etomidate as 0.2μg/ml. The concentration was increased by steps until the patient was asleep, (OAAS class Ⅰ-Ⅱ), then gave fentanyl 3μg/kg and rocuronium 0.6 mg/kg and intubated three minutes later. The patients' age, height, and weight were recorded.BIS was recorded before induction, at the initial effect-site concentration and at loss of consciousness. The effect-site concentration was recorded when patient lost consciousness.Results There were no significant differences between groups in general conditions before treatment; such as BIS of consciousness, age, sex and body mass index. The EC50 of propofol in the NP, TP and CP groups was 4.11 μg/ml (95%CI: 3.96-4.26), 2.94 μg/ml (95% CI: 3.36-3.47) and 2.91 μg/ml (95% CI: 3.35-3.86), respectively. The EC50 of etomidate in the NE, TE and CE groups was 0.61 μg/ml (95% CI: 0.55-0.67), 0.38

  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. Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Jiang-hua ZHONG; Xiao-pan CHEN; Mei-ling YUN; Wei-jing LI; Yan-fang CHEN; Zhen YAO

    2007-01-01

    Aim: To study the effects of carvedilol on the transmural heterogeneity of ven-tricular repolarization in rabbits with congestive heart failure (CHF). Methods:Rabbits were randomly divided into 3 groups: control, CHF and carvedilol treated CHF group. Monophasic action potential duration (MAPD) in the 3 myocardial layers was simultaneously recorded. Results: All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resis-tance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold (VFT) was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization (TDR) was significantly increased in CHF.Low-dose carvedilol (0.25 mg/kg, twice daily) had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Al-though the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF. Conclusion: In the present study, the trans-mural heterogeneity of ventricular repolarization increased in the rabbits with CHF. Low-dose carvedilol decreased the transmural heterogeneity of ventricular repolarization in CHF, which may be related to its direct electrophysiological pro-perty rather than its effect on ventricular remodeling.

  19. SCREENING OF DRUG RESISTANCE-RELATED GENES FROM HUMAN OVARIAN CANCER CELL LINE OC3/ADR BY DD-PCR

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    田方; 程国均; 周海胜; 王宏; 肖凤君

    2001-01-01

    Objective: To screen novel genes related to adriamycin (Adr) resistance from human ovarian cancer resistance cell line OC3/Adr. Methods: Multidrug resistant ovarian cancer cell line OC3/Adr was induced by intermittent treatment of the human parent cell line OC3 with high concentration Adr. The difference of gene expression was screened by using different display analysis to the acquired Adr-resistance subline OC3/Adr and its parent cell line OC3. Results: OC3/Adr cell line was obtained which was more resistance to Adr than the parent cell line OC3 with the resistance index (RI) of 15.4. The OC3/Adr cell line also showed cross-resistance to other anti-cancer drugs (VP16, CDDP,5FU ). It grew slowly and exhibited changes of cell cycle. A number of differentially expressed ESTs (Expressed Sequence Tags, ESTs) were identified at mRNA level between the OC3/Adr and OC3. Four of 18 different ESTs were sequenced. The 431/432 base pair S1 was homologous to human sperm zona pellucida binding protein, while the other two ESTs, S3 and S4, were new gene segments, which were registered to GenBank with the number of AF 117656 and AF 126507 respectively. Particularly, the expression of S2 sequence increased in all the drug-resistance cell lines and S3 sequence overexpressed in human ovarian cancer tissues as compared with benign ovarian tumors. Adr in ovarian cancer OC3/Adr is involved with changes of multiple gene expressions.

  20. 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.

  1. Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay

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    Fehm Tanja

    2012-07-01

    Full Text Available Abstract Background The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA. Methods Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50, for IC90 and for the sensitivity index (IndexSUM. Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls. Results The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8% and TAC (12.9%, respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p  Conclusion Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer.

  2. 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

  3. Correlation of Baseline BCL-2 mRNA Expression and Clinical Response to Neoadjuvant Chemotherapy in Breast Cancer

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    Prihantono Prihantono

    2017-01-01

    Full Text Available Impairment of apoptosis is a hallmark of cancer. Tumor resistance to apoptosis usually caused by deregulation of the expression of BCL-2 family protein or mutation of the tumor suppressor gene p53. Over expression of Bcl-2 is commonly found in various types of cancer including breast cancer. Studies mentioned that analysis of Bcl-2 might predict response to selected endocrine and chemotherapies. This study is conducted to evaluate the correlation of BCL-2 mRNA expression and clinical response to neoadjuvant chemotherapy in breast cancer patients. Longitudinal study is used in this research, 30 subjects of breast cancer tissue samples prechemotherapy using cyclophosphamide-adriamycin-5FU regiment. Detection of mRNA expression of BCL-2 using qRT-PCR techniques. Evaluation of clinical response to chemotherapy is using RECIST criteria. Mean value of BCL-2 mRNA expression in breast cancer patients was 9.917± 2.568. Mean value of BCL-2 mRNA expression of responsive group was 9.887± 2.731. Mean value of BCL-2 mRNA expression of nonresponsive group was 10.017±2.122. Mean value of responsive group were lower than nonresponsive group, but there was no significant correlation between baseline mRNA expression of BCL-2 with clinical response to chemotherapy, value of r=0.378, p=0.223 (p>0.05. this study shows that there was no significant correlation between baseline expression of mRNA BCL-2 with clinical response to chemotherapy.

  4. 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.

  5. Proliferative Inhibition of Rabbit Lens Epithelial Cell—Preliminary Investigation for Prevention of After Cataract

    Institute of Scientific and Technical Information of China (English)

    XiaoboSu; ShaozhenLi

    1995-01-01

    Purpose:To study the ability of Homoharringtonine(Hh),5-Fluorouracil(5-Fu).and Adriamycin(ADM)on inhibiting the proliferation of rabbit lens epitthelium,Methods.Whole rabbit lenses were removed from freshly enucleated eyes under sterile condition.The rabbit lens eptithlia(RLE)were isolated and culatured:(1)The passage RLE were placed in 24-well tissue culture plates and incubated for 48hours.then exposed to different concentrations of Hh,5-Fu,and ADMfor 24and 72hours;(2)The passage RLEandHh(0.084μg/ml).5-Fu(0.058μg/ml),ADM(0.45ng/ml)were placed and cultured for 24hours;(3)The morphological changes of RLE exposed to different concentrations of Hh,5-Fu and ADM were studied under light microscope.Results:The ID50 of Hh,5-Fu and ADMexposed to RLEfor 24hours were 0.84μg/ml, 0.58μg/ml and4.50ng/ml,respectively,and those for 72hous were0.49μg/ml,0.33μg/ml and3.85ng/ml.The attachment rate of RLE after being cu-latured for 24hours with Hh,5-Fu and ADM were respectinely83.6%,89.1%and 87.3%,The morphological changes of RLE demonstrated that obvious changes in the cell membran e and cytoplasm were found even in lower concentra-tion ,but changes in the nuclei could only be found in higher concentation of these drugs.Conclusion:Hh can not only inhibit the proliferation of RLE but also reduce the number of attached cells.It is suggested that Hh may be more useful for the pre-vention of after cataract than 5-Fu and ADM.

  6. Association between DNA methylation and multidrug resistance in human glioma SHG-44 cells.

    Science.gov (United States)

    Chen, Jin; Xu, Zhong-Ye; Wang, Feng

    2015-01-01

    The aim of the present study was to evaluate the association between DNA methylation and multidrug resistance (MDR) in glioma and identify novel effectors responsible for MDR in human gliomas. An MDR glioma cell line, SGH-44/ADM, was developed using adriamycin (ADM) impulse treatment. Cryopreservation, recovery and withdrawal were performed to evaluate the stability of SGH-44/ADM cells. The adherence rate and cellular morphology were observed by microscopy, and the cell growth curve and doubling time were determined. DNA methylation was analyzed using a methylated DNA immunoprecipitation microarray chip (MeDIP-Chip). The cell cycle, Rh123 ingestion and exudation, and SGH-44/ADM apoptosis were analyzed by flow cytometry. SGH-44/ADM cells showed little difference as compared with parental cells, except that SGH-44/ADM cells were bigger in size with a wizened nucleus. Compared to SGH-44 cells, a larger proportion of SGH-44/ADM cells remained in G1 and S phase, as measured by flow cytometry. The MDR of SGH-44/ADM was associated with the upregulation of multi-drug resistance 1, prostaglandin-endoperoxide synthase 2 (COX-2); protein kinase C α (PKCα); however, the expression of these genes was not associated with DNA methylation. In the MeDIP-Chip analysis, 74 functions were markedly enhanced, and seven significant pathways were observed. Genes including SNAP47, ARRB2, PARD6B, TGFB1, VPS4B and CBLB were identified by gene ontology analysis. The predominant molecular mechanism of MDR in SGH-44/ADM cells was identified as exocytosis and efflux. The expression of COX-2, PKCα and P-glycoprotein (Pgp) was not found to be associated with DNA methylation. Genes including SNAP47, VAMP4 and VAMP3 may serve as the downstream effectors of Pgp, COX-2 or PKCα; however, further experiments are required to verify these observations.

  7. Reversal effect and mechanism of Ginkgo biloba exocarp extracts in multidrug resistance of mice S180 tumor cells

    Science.gov (United States)

    Hu, Bi-Yuan; Gu, Yun-Hao; Cao, Chen-Jie; Wang, Jun; Han, Dong-Dong; Tang, Ying-Chao; Chen, Hua-Sheng; Xu, Aihua

    2016-01-01

    The aim of the present study was to investigate the reversal effect and its related mechanism of Ginkgo biloba exocarp extracts (GBEEs) in obtained multidrug resistance (MDR) of mice S180 tumor cells in vitro and in vivo. In order to simulate the clinical PFC [cis-dichlorodiamineplatinum, cisplatin (DDP) + fluorouracil (FU), FU+cyclophosphamide and cyclophosphamide] scheme, a gradually increasing dose was administered in a phased induction in order to induce S180 cells in vivo and to make them obtain multidrug resistance. The results in vitro demonstrated that GBEE could significantly increase the IC50 of DDP on S180 MDR cells, increase the accumulation of Adriamycin (ADR) and rhodamine 123 (Rho 123), and reduce the efflux of Rho 123 of S180 MDR cells. The results from the in vivo treatment with a combination of GBEE and DDP to S180 MDR ascites tumor in mice demonstrated that each dose of GBEE could effectively reverse the drug-resistance of S180 MDR cells to DDP in order to extend the survival time of mice with ascite tumors and inhibit tumor growth in solid tumor mice. In addition, GBEE effectively inhibited the expression of MDR-1 mRNA and multidrug resistance-associated protein-1 mRNA in S180 MDR cells of ascites tumor in mice and improved the expression levels of cytokines, including interleukin (IL)-3, IL-18 and interferon-γ in the blood serum of S180 MDR tumor-bearing mice. The present study showed that the mechanism of GBEE reversal of MDR may be associated with the inhibition of the functional activity of P-glycoprotein, the downregulation of drug resistance related gene expression of S180 MDR cells and the improvement of the production of related serum cytokines of S180 MDR tumor mice. PMID:27698692

  8. Long Non-Coding RNA (LncRNA) Urothelial Carcinoma Associated 1 (UCA1) Increases Multi-Drug Resistance of Gastric Cancer via Downregulating miR-27b

    Science.gov (United States)

    Fang, Qun; Chen, XiaoYan; Zhi, XuTing

    2016-01-01

    Background In this study, we aimed to investigate the association between UCA1 and miR-27b in gastric cancer and further study their involvement in multi-drug resistance (MDR) of gastric cancer. Material/Methods The microarray data of dysregulated lncRNAs in gastric cancer tissues was retrieved in the GEO dataset. QRT-PCR analysis was performed to assess UCA1 expression based on 28 paired cancerous and peritumoral normal tissues. The human gastric cancer cell line SGC-7901, and SGC-7901 derived Adriamycin (doxorubicin) resistant SGC-7901/ADR, cisplatin resistant SGC-7901/DDP, and 5-FU resistant SGC-7901/FU cells were used as in vitro cell models to assess the effect of UCA1 and miR-27b on MDR. Results UCA1 was significantly upregulated in the cancerous tissues and its expression was negatively correlated with miR-27b expression level. Inhibition of UCA1 significantly restored miR-27b expression in MDR gastric cancer cells. UCA1 knockdown and miR-27b overexpression reduced IC50 of ADR, DDP, and 5-FU in SGC-7901/ADR cells and increased ADR induced cell apoptosis. UCA1 overexpression and miR-27b inhibition increased the IC50 of ADR, DDP, and 5-FU in SGC-7901 cells and reduced ADR induced cell apoptosis. Western blot analysis showed that UCA1 knockdown and miR-27b overexpression also decreased anti-apoptotic protein BCL-2 and increased apoptotic protein cleaved caspase-3. Conclusions UCA1 is negatively correlated with miR-27b expression in gastric cancer tissue. Knockdown of UCA1 restored miR-27b expression in gastric cancer cells. The UCA1-miR-27b axis was involved in regulation of chemosensitivity of gastric cancer cells. PMID:27694794

  9. Enhanced DNA repair and tolerance of DNA damage associated with resistance to cis-diammine-dichloroplatinum (II) after in vitro exposure of a human teratoma cell line to fractionated X-irradiation

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    Hill, B.T.; Shellard, S.A.; Hosking, L.K.; Fichtinger-Schepman, A.M.; Bedford, P. (Imperial Cancer Research Fund, Lincoln' s Inn Fields, London (England))

    1990-07-01

    In vitro exposure of a human testicular teratoma continuous cell line to fractionated X-irradiation resulted in the expression of resistance to cisplatin. In two independently-derived sublines, designated SUSA-DXR13 and SUSA-DXR10 resulting from treatment with either 13 fractions of 1.5 Gy (dose required to reduce survival by 1 log) or 10 fractions of 3 Gy (dose required to reduce survival by 2 logs) respectively, the IC50 values for cisplatin were 2- and 3.1-fold higher than that of the parental cell line. These sublines were cross-resistant to carboplatin (approximately 2-fold) but not to adriamycin and they showed unaltered radiosensitivities. The SUSA-DXR10 subline expressed some cross-resistance to mitomycin C and melphalan but none to Carmustine (BCNU). Total glutathione content was significantly reduced in both SUSA-DXR10 and SUSA-DXR13 cells, but the activities of associated enzymes, including the glutathione S-transferases, peroxidase and reductase were not modified significantly in the resistant sublines. Resistance in the SUSA-DXR10 subline was associated with significantly decreased 195mcisplatin uptake (p less than 0.01), but this was not reflected in a reduced level of drug bound to the DNA. The formation and removal of four platinum-DNA adducts were immunochemically quantitated. Immediately following drug treatment there was a higher level of total platination of the DNA in the resistant subline indicative of increased tolerance to DNA damage. After an 18 hr post treatment incubation, there was an indication of some repair capacity in this SUSA-DXR10 cell line, which was not apparent in the parental cells. Neither the parental nor the SUSA-DXR10 cell line was proficient in the repair of the major adduct Pt-GG, whereas both lines repaired the monofunctional adduct and the adduct Pt(GMP)2.

  10. Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors.

    Science.gov (United States)

    Waks, Adrienne G; Tolaney, Sara M; Galar, Alicia; Arnaout, Amal; Porter, Julie B; Marty, Francisco M; Winer, Eric P; Hammond, Sarah P; Baden, Lindsey R

    2015-11-01

    Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been recognized as a significant complication of early-stage breast cancer treatment. However, we have observed an increase in PCP incidence among patients receiving chemotherapy for early-stage breast cancer. Herein we identify risk factors for and calculate incidence of PCP in this population. We identified all cases of PCP at Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH) from 1/1/2000 to 12/31/2013 in patients with stage I-III breast cancer treated with an adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non-metastatic breast cancer patients were identified. All patients with PCP were diagnosed after receipt of either three or four cycles of AC chemotherapy on a dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg prednisone equivalents/day as nausea prophylaxis for a median 64 days. The overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3-1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC. There was one death from PCP. Women receiving dose-dense AC chemotherapy for early-stage breast cancer are at risk for PCP. Administering the same chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense schedule appears to have created a novel infectious vulnerability. Replacing dexamethasone with alternative anti-emetics may mitigate this risk.

  11. Augmented Berlin-Frankfurt-Münster Therapy in Adolescents and Young Adults (AYA) with Acute Lymphoblastic Leukemia (ALL)

    Science.gov (United States)

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

    2014-01-01

    Background Various trials report improved outcomes for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric- based regimens. This prompted the investigation of the pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen in AYA patients. Results were compared with the hyper–fractionated cyclophosphamide, vincristine, Adriamycin and dexamethasone (hyper-CVAD) regimen in a similar population. Methods Eighty-five patients age 12 to 40 years with Philadelphia chromosome- (Ph) negative ALL were treated with ABFM from 10/2006 through 4/2012. Their outcome was compared to 71 historical AYA patients treated with hyper-CVAD from our institution. Patient and disease characteristics, as well as status of minimal residual disease (MRD), were analyzed for their impact on outcomes. Results The complete remission (CR) rate with ABFM was 94%. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 70% and 74%, respectively. The 3-year CRD and OS were 72% and 85%, respectively, with age ≤ 21 years, and 69% and 60%, respectively, with age 21-40 years. Initial white blood cell count was an independent predictive factor of OS and CRD. The MRD status on Day 29 and Day 84 of therapy were also predictive of long-term outcomes. Severe regimen toxicities included transient hepatotoxicity in 35-39%, pancreatitis in 11%, osteonecrosis in 11%, and thrombosis in 22%. The 3-year OS rate was 74% with ABFM versus 71% with hyper-CVAD; the 3-year CRD rate was 70% with ABFM versus 66% with hyper-CVAD. Conclusion ABFM was tolerable in AYA patients with ALL but was not associated with significant improvements in CRD and OS compared with hyper-CVAD. PMID:25042398

  12. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

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    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.

  13. 不同序贯的吉非替尼与化疗药物联合对人肝癌细胞Bel-7402增殖的抑制作用%Sequence-Dependent Antiproliferative Effects of Gefitinib and Cytotoxic Drugs on Bel- 7402 Cells

    Institute of Scientific and Technical Information of China (English)

    魏超; 周乃珍; 郭慧; 朱联九; 张盛周

    2011-01-01

    The inhibitory effects of gefitinib combining with different concentrations of adriamycin, fluorouracil, cisplatin and paclitaxel in different sequences on the proliferation of Bel - 7402 cells were evaluated by MTT assay. The results showed that the inhibitory effect of cytotoxic drug combining with gefitinib was better than that of cytotoxic drug treatment alone, the IC50 decreased significantly. The antiproliferative effects of drug combination were affected by different drug sequences, gefitinib used after cytotoxic drugs created better curative effects than that before cytotoxic drugs. These results provided helpful information for hepatocellular carcinoma clinical therapy, they could conduce to less doses and toxic effects in clinical application.%应用MTT法检测了靶向性药物吉非替尼(gefitinib)分别与阿霉素(ADM)、氟尿嘧啶(5-FU)、顺铂(DDP)和紫杉醇(PTX)等4种化疗药物按照不同给药序贯联合作用对肝癌细胞Bel-7402增殖的影响.结果表明,吉非替尼与4种化疗药物联用对Bel-7402细胞增殖的抑制作用效果均要好于单药治疗,其对细胞的IC50较单独用药时明显较低.联合用药效果受到给药序贯的影响,用靶向性药物前先用化疗药物的效果要好于先用靶向性药物后用化疗药物.研究结果可供肝癌临床治疗参考,有助于临床降低用药剂量,减轻药物毒副作用.

  14. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

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    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.

  15. Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

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    Singh Tej B

    2007-08-01

    Full Text Available Abstract Background Doppler ultrasonography (US is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. Methods Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1–4 for 50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. Results The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7% had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. Conclusion Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological

  16. Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

    Science.gov (United States)

    Kumar, Anand; Singh, Seema; Pradhan, Satyajit; Shukla, Ram C; Ansari, Mumtaz A; Singh, Tej B; Shyam, Rohit; Gupta, Saroj

    2007-01-01

    Background Doppler ultrasonography (US) is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. Methods Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil) chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1–4 for 50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. Results The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7%) had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. Conclusion Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological response. PMID:17725837

  17. (Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis.

    Science.gov (United States)

    Li, Zhen; Zhou, Lili; Wang, Yongping; Miao, Jinhua; Hong, Xue; Hou, Fan Fan; Liu, Youhua

    2017-03-07

    The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/β-catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β-catenin induced PRR mRNA and protein expression in vitro Notably, forced expression of PRR potentiated Wnt1-mediated β-catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α-smooth muscle actin (α-SMA). Conversely, knockdown of PRR by siRNA abolished β-catenin activation. PRR potentiation of Wnt/β-catenin signaling did not require renin, but required vacuolar H(+) ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β-catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/β-catenin signaling.

  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. 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

  20. Vascular endothelial growth factor induces multidrug resistance-associated protein 1 overexpression through phosphatidylinositol-3-kinase/protein kinase B signaling pathway and transcription factor specificity protein 1 in BGC823 cell line

    Institute of Scientific and Technical Information of China (English)

    Juan Li; Xiaojun Wu; Jinling Gong; Jing Yang; Jiayan Leng; Qiaoyun Chen; Wenlin Xu

    2013-01-01

    Multidrug resistance (MDR) is one of the most important causes of chemotherapy failure and carcinoma recurrence.But the roles of the MDR-associated protein MRP1 in MDR remain poorly understood.Vascular endothelial growth factor (VEGF),one of the most active and specific vascular growth factors,plays a significant role in proliferation,differentiation,and metastasis of cancers.To explore the effect of VEGF on the expression of MRP1,we used recombinant human VEGF to stimulate K562 and BGC-823 cell lines.Quantitative real-time polymerase chain reaction and western blot analysis showed that the expression of MRP1 at both mRNA and protein levels was increased.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide results also showed that VEGF significantly enhanced the ICs0 of the cells treated with adriamycin.To explore the underlying regulatory mechanisms,we constructed MRP1 promoter and the luciferase reporter gene recombinant vector.The luciferase reporter gene assay showed that the activity of the MRP1 promoter was markedly increased by VEGF stimulation,while LY294002,an inhibitor of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway,reduced this effect.Transcription factor specificity protein 1 (SP1) binding site mutation partially blocked the up-regulation of MRP1 promoter activity by VEGF.In summary,our results demonstrated that VEGF enhanced the expression of MRP1,and the PI3K/Akt signaling pathway and SP1 may be involved in this modulation.

  1. Analysis of Efficacy of DICE (Dexamethasone, Ifosfamide,Cisplatin and Etoposide) Regimen on Recurrent and Refractory Intermediate and High Grade Non-Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Zhucheng Song; Xiaohong Xu; Jinzhi Wei; Qinghe Tan; Zhirong Cong; Chunlei Peng

    2009-01-01

    OBJECTIVE Thus far there is no standard salvage regimen for patients with recurrent and refractory intermediate and high grade non-Hodgkin's lymphoma (NHL). This study intends to investigate the therapeutic efficacy of the DICE (dexamethasone, isofosfamide, cisplatin and etoposide) regimen on the recurrent and refractory NHL, and to observe the related adverse effects. METHODS Clinical records of 22 patients with recurrent and refractory NHL, who failed to achieve a remission from the CHOP [cyclophosphamide, hydroxydaunomycin/doxorubicin (adriamycin), oncovin, prednisone] regimen within 2 to 6 cycles of treatment, were reviewed. DICE, as a salvage regimen with a median course of treatment of 4 cycles (ranging from 2 to 7 cycles), was now used, and evaluation of the therapeutic efficacy and adverse effect of DICE was conducted in all the patients. Of the 22 NHL cases, 8 were of T-cell origin and the other 14 B-cell origin. Salvage treatment was performed in the patients, with appraisal, prevention and treatment of the toxic reactions. RESULTS Following DICE treatment in the 22 patients, the total effective rate of the regimen was 63.6%, and the complete remission (CR) rate was 40.9%. The effective rates of DICE on the T and B-cell sourced NHL were 75.0% and 57.1%, and the CR rate were 37.5%, 42.9%, respectively (P > 0.05). An increase of the lactate dehydrogenase (LDH) level accompanied by a giant lump was the short-term effect on patients with recurrence (mean P < 0.05) who were drug resistant. Myelosuppression, digestive system reaction and alopecia were the commonly-seen complications in the patients who Received DICE regimen. All patients recovered after treatment, and no chemotherapy-related death occurred. CONCLUSION DICE regimen is effective in treating refractory and recurrent NHL.

  2. Adenovirus replication as an in vitro probe for drug sensitivity in human tumors.

    Science.gov (United States)

    Parsons, P G; Maynard, K R; Little, J H; McLeod, G R

    1986-04-01

    The feasibility of using adenovirus 5 as an in vitro probe for chemosensitivity in short-term cultures of human tumors was evaluated using human melanoma cell lines and primary cultures of melanoma biopsies. A convenient immunoperoxidase method was developed for quantitating viral replication 2 days after infection. Two different approaches were explored: the host cell reactivation assay (HCR) using drug-treated virus; and the viral capacity assay using drug-treated cells. The HCR assay detected sensitivity to 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC) in Mer- (methyl excision repair deficient) cell lines as decreased ability of the cells to replicate MTIC-treated virus. This test should be applicable to DNA-damaging agents and repair-deficient tumors. Adenovirus replicated readily in nonproliferating primary cultures of melanoma biopsies; application of the HCR assays to this material identified one Mer- sample of 11 tested. Herpes viruses were not suitable for use in HCR because herpes simplex virus type 1 failed to distinguish Mer- from Mer+ melanoma cells; and nonproductive infection of MTIC-sensitive lymphoid cells with Epstein-Barr virus yielded an MTIC-resistant cell line. The second assay (viral capacity) involved determination of the inhibition of replication of untreated virus in treated cells. This approach correctly predicted sensitivity to hydroxyurea and deoxyadenosine in melanoma cell lines when compared with clonogenic survival assay. Viral capacity was also inhibited by cytosine arabinoside, fluorouracil, vincristine, adriamycin, 6-mercaptopurine and ionising radiation, and may therefore be useful for detecting sensitivity to a wide range of antitumor agents.

  3. Preoperative balloon occluded arterial infusion chemotherapy for locally invasive bladder cancer. Accurate staging for bladder preservation

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    Hayashi, Norio; Arima, Kiminobu; Kawamura, Juichi [Mie Univ., Tsu (Japan). School of Medicine; Tochigi, Hiromi

    1999-02-01

    The possibility of bladder preservation by preoperative balloon occluded arterial infusion (BOAI) chemotherapy was studied in 111 patients with locally invasive bladder cancer. BOAI was performed by blocking the blood flow of the internal iliac artery and by performing intra-arterial infusion of adriamycin (50 mg/body) and cisplatin (100 mg/body). Before BOAI the clinical diagnosis was T2 in 36, T3a in 29, T3b in 27, T4 in 11 and after BOAI it was T0 in 1, T1 in 27, T2 in 25, T3a in 20, T3b in 20, and T4 in 10. Down staging was observed on diagnostic images in 46.6%. Thirty patients (27.0%) received transurethral resection of bladder tumor (TUR-Bt) and their bladder could be preserved. The 5-year cancer-specific survival rate was 100% in pT0 (n=9), 97.5% in pT1 (n=47), 79.9% in pT2 (n=21), 80.0% in pT3a (n=6), 39.9% in pT3b (n=18) and 51.9% in pT4 cases (n=9). For the bladder preservation, accurate staging diagnosis is required. Since 1992, endorectal magnetic resonance imaging (MRI) has been used in addition to imaging diagnosis for improving the accuracy of staging diagnosis. The accuracies of staging diagnosis with and without endorectal MRI were 62.5% and 44.0%, respectively. BOAI as a neoadjuvant chemotherapy has the possibility of bladder-preserving therapy in locally invasive bladder cancer. Also, the endorectal MRI can improve the accuracy of staging diagnosis, which is important for the bladder preservation. (author)

  4. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

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    Xiaoying Li

    Full Text Available Our previous in vitro studies suggested that cyclic AMP (cAMP signaling prevents adriamycin (ADR and puromycin aminonucleoside (PAN-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA or exchange protein directly activated by cAMP (Epac pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator, PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  5. Long term (five-year survival following radical surgical treatment plus adjuvant chemotherapy (FAM in advanced gastric cancer: a controlled study

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    Bresciani Cláudio

    2000-01-01

    Full Text Available Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment. The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification. A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM (5-fluorouracil, Adriamycin, and mitomycin C. In this latter group, chemotherapy toxicity in relation to hepatic, renal, cardiologic, neurological, hematologic, gastrointestinal, and dermatological functions was also studied. There was no significant difference on admission between both groups in relation to gender, race, macroscopic tumoral type of tumor according to the Borrmann classification, location of the tumor in the stomach, length of the gastric resection, or response to cutaneous tests on delayed sensitivity. Chemotherapy was started on average, 2.3 months following surgical treatment. Clinical and laboratory follow-up of all patients continued for 5 years. The following conclusions were reached: 1 The nutritional status and incidence of gastrointestinal manifestation were similar in both groups; 2 There was no occurrence of cardiac, renal, neurological, or hepatic toxicity or death due to the chemotherapeutic method per se; 3 Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy; 4 There was no significant difference between the rate and site of tumoral recurrence, the disease-free interval, or the survival rate of both study groups; 5 Therefore, we concluded, after a 5-year follow-up, chemotherapy with the FAM regimen did not increase the survival rate.

  6. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    Science.gov (United States)

    Carrara, Guilherme Freire Angotti; Scapulatempo-Neto, Cristovam; Abrahão-Machado, Lucas Faria; Brentani, Maria Mitzi; Nunes, João Soares; Folgueira, Maria Aparecida Azevedo Koike; da Costa Vieira, René Aloisio

    2017-01-01

    OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors. PMID:28355358

  7. Reversal effect and mechanism of Ginkgo biloba exocarp extracts in multidrug resistance of mice S180 tumor cells.

    Science.gov (United States)

    Hu, Bi-Yuan; Gu, Yun-Hao; Cao, Chen-Jie; Wang, Jun; Han, Dong-Dong; Tang, Ying-Chao; Chen, Hua-Sheng; Xu, Aihua

    2016-10-01

    The aim of the present study was to investigate the reversal effect and its related mechanism of Ginkgo biloba exocarp extracts (GBEEs) in obtained multidrug resistance (MDR) of mice S180 tumor cells in vitro and in vivo. In order to simulate the clinical PFC [cis-dichlorodiamineplatinum, cisplatin (DDP) + fluorouracil (FU), FU+cyclophosphamide and cyclophosphamide] scheme, a gradually increasing dose was administered in a phased induction in order to induce S180 cells in vivo and to make them obtain multidrug resistance. The results in vitro demonstrated that GBEE could significantly increase the IC50 of DDP on S180 MDR cells, increase the accumulation of Adriamycin (ADR) and rhodamine 123 (Rho 123), and reduce the efflux of Rho 123 of S180 MDR cells. The results from the in vivo treatment with a combination of GBEE and DDP to S180 MDR ascites tumor in mice demonstrated that each dose of GBEE could effectively reverse the drug-resistance of S180 MDR cells to DDP in order to extend the survival time of mice with ascite tumors and inhibit tumor growth in solid tumor mice. In addition, GBEE effectively inhibited the expression of MDR-1 mRNA and multidrug resistance-associated protein-1 mRNA in S180 MDR cells of ascites tumor in mice and improved the expression levels of cytokines, including interleukin (IL)-3, IL-18 and interferon-γ in the blood serum of S180 MDR tumor-bearing mice. The present study showed that the mechanism of GBEE reversal of MDR may be associated with the inhibition of the functional activity of P-glycoprotein, the downregulation of drug resistance related gene expression of S180 MDR cells and the improvement of the production of related serum cytokines of S180 MDR tumor mice.

  8. Treatment of advanced breast cancer with chinese medicinal herbs of Fei decoction: a case report.

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    Lv, G M; Hu, M; Chen, R Z; Zhu, L L; Tao, Ch J; Xia, X D; Gong, Y L; Li, P; Wan, H J

    2014-01-01

    A 46-year-old female underwent surgery for cancer of the right breast mammary (T3N2M0) in Sep 2010. Following post surgery, adjuvant chemotherapy of CAF regimens (cyclophosphamide+adriamycin+fluorouracil) was administered. Two years later, multiple pulmonary and skeletal metastatic lesions had been found by CT (computerized tomography) and ECT (emission computed tomograph) imaging. She received the treatment of second-line chemotherapy regimens of GP (cisplatin + gemcitabine). In the meantime, we administered Chinese traditional herb drugs (Fei Decoction, mixed a variety of effective herbal components) to help her recover from the poor condition. After taking the Chinese herbs for 2 months, the tumour marker (CEA, CA15-3) dramatically decreased, resulting in the normal range. Both lung and bone metastatic sites reduced according to CT and ECT imaging, and the patient felt free from the complaint of pulmonary and cardiac discomfort. Over time, the quality of life has been greatly improved, we have managed to prolong the PFS (progression-free-survival) and TTP (time-to-progression) from the onset to date. CTM (Chinese traditional medicine) considers human body as a dynamic platform in which all organs are correlative and bind each other. Relationship between heart, liver, spleen, lung and kidney is like an interlink between mother and son, and runs in cycle as a circle. In the course of this combined treatment, we showed that Chinese herbal medicine played an important role in the therapy of breast cancer. Chinese herbs might be an additional choice with their better benefits and tolerability in the treatment of recurrent breast cancer.

  9. Effects of multidrug resistance, antisense RNA on the chemosensitivity of hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Bo Li; Jian-Ping Gong; Tian Ye; Lei Zhao; De-Hua Li; Xing-Hua Gou; Lan-Ying Zhao; Lei Han; Lin Chen; Lu-Nan Yan

    2006-01-01

    BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM. METHODS: The recombinant adenoviruses pAdEasy-GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene. Following that, the recombinant adenovirus was transfected into the P-glycoprotein-producing multidrug resistance cell line, SMMC7721/ADM human HCC cells resistant to adriamycin (ADM) and daunorubicin (DNR). In order to investigate the reversal of multidrug resistance phenotype, we measured the expression of mdr1 mRNA by RT-PCR and the production of P-glycoprotein by lfow cytometry. The sensitivities for ADM and DNR SMMC7721/ADM cells were examined by [3-(4, 5-dimethylthi-azol-2-yl)-2,5 diphenyl-terazolium bromide] (MTT) analysis. RESULTS: The low-level expression of mdr1 mRNA and P-glycoprotein production were observed in parental sensitive cells SMMC/7721 in addition to the overexpression of mdr1 mRNA and P-glycoprotein in SMMC7721/ADM cells. The transfection of antisense-RNA into SMMC7721/ADM cells resulted in decreases of mdr1 mRNA and P-glycoprotein, but increase of drug sensitivities. The sensitivities of transfected SMMC7721/ADM cells to ADM and DNR in IC50 reduced by 31.25% and 62.96%respectively. CONCLUSIONS: Mdr1 antisense RNA can increase the sensitivities of SMMC7721/ADM cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression. This strategy may be applicable to cancer patients with P-glycoportein mediated multidrug resistance.

  10. Non-Hodgkin′s lymphoma: Is India ready to incorporate recent advances in day to day practice?

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    Vallabhajosyula Saraschandra

    2010-01-01

    Full Text Available Background : Non Hodgkin′s Lymphoma (NHL cure rates are increasing and morbidities are decreasing, with more active pharmacological agents and technological advancements. In spite of this, India is still battling with the prejudices of an economically and educationally impoverished patient base. Methods and Results : We analyzed NHL cases from 2000 to 2006 using data from case sheets. Of 303 cases, only 100 patients had complete workup and received some form of treatment. For 203 patients, reasons for non-compliance were: financial constraint (119, distance from center (38, inability of physician to provide guarantees of cure (13, poor prognosis/fear of recurrence (28, preferences for alternate medicine (5. Most common investigations that could not be afforded for staging were whole body CT scans and bone marrow aspiration and biopsy. Thirteen patients were in stage III and 53 in Stage IV. The most common regimen was CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisolone. Forty-five patients did not complete six courses of CHOP and 35 patients had significant delay. Reasons for delay were intermittent availability of cash (35, intolerable toxicities (30, absence of supportive care (21, given-up attitudes (17. Eighty-three patients suffered Grade III/IV debilitating toxicities. Overall survival at five years was 50%. Conclusions : NHL in India is no different from the developed world. However, there are disparities in survivorship and outcomes, due to un-affordability and attitudes of the patients. Therefore, we suggest the development of Community Health Insurance Schemes (CHIs, with the hospital as the nodal center to address the above mentioned issues.

  11. Clinical application of l-123 MlBG cardiac imaging

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    Kang, Do Young [College of Medicine, Donga Univ., Busan (Korea, Republic of)

    2004-10-01

    Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MlBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with l-123 MlBG imaging may be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy.

  12. 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.

  13. Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production.

    Science.gov (United States)

    Vistica, D T; Skehan, P; Scudiero, D; Monks, A; Pittman, A; Boyd, M R

    1991-05-15

    The hydrogen acceptor 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) is commonly utilized to estimate cellular viability in drug screening protocols. The present investigation was prompted, in part, by observations that reduction of MTT to its colored reaction product, MTT formazan, varied between cell lines and with culture age. A correlation was established between the D-glucose concentration of the culture medium at the time of assay and the production of MTT formazan for cell lines representing seven tumor histologies. A decrease in the concentration of D-glucose from culture medium was accompanied by a decrease in MTT specific activity (MTT formazan/microgram cell protein) for a number of cell lines. Cells which extensively metabolized D-glucose exhibited the greatest reduction in MTT specific activity. Further evidence that the D-glucose concentration of the culture medium played an important role in MTT reduction was provided by experiments which demonstrated that transfer of cells to a glucose-free medium (L-15) was accompanied by an immediate decrease in MTT reduction which was pH independent. These studies suggested that cellular transport and constant metabolism of glucose were required for maximum MTT reduction. Decreases in the cellular concentration of the reduced pyridine nucleotides NADH and NADPH were accompanied by concomitant decreases in MTT formazan production. MTT formazan varied significantly among cell lines in both the kinetics of its formation and the degree of saturability exhibited. Apparent IC50 values for Adriamycin varied, in a cell line-specific manner, with MTT exposure time. These results indicate that MTT specific activity is significantly influenced by a number of parameters and suggest that assay conditions should be established which minimize their effects.

  14. 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.

  15. Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

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    Chim Chor

    2012-06-01

    Full Text Available Abstract Background We have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone before autologous stem cell transplantation (ASCT. Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone or VTD (bortezomib/thalidomide/dexamethasone induction, and analysed prognostic factors for outcome. Patients and methods Ninety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25, PAD (N = 31, VTD (N = 35]. and received thalidomide maintenance for 2 years post-ASCT. Results 43 (47.3% patients had International Staging System (ISS III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS and event-free (EFS survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS. Conclusions These three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

  16. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

    Science.gov (United States)

    Li, Xiaoying; Tao, Hua; Xie, Kewei; Ni, Zhaohui; Yan, Yucheng; Wei, Kai; Chuang, Peter Y; He, John Cijiang; Gu, Leyi

    2014-01-01

    Our previous in vitro studies suggested that cyclic AMP (cAMP) signaling prevents adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA) or exchange protein directly activated by cAMP (Epac) pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator), PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  17. Angiopoietin-Like-4, a Potential Target of Tacrolimus, Predicts Earlier Podocyte Injury in Minimal Change Disease.

    Science.gov (United States)

    Li, Jian-Si; Chen, Xiao; Peng, Lei; Wei, Shi-Yao; Zhao, Shi-Lei; Diao, Tian-Tian; He, Yi-Xin; Liu, Fang; Wei, Qiu-Ju; Zhang, Qing-Fang; Li, Bing

    2015-01-01

    Podocyte injury plays central roles in proteinuria and kidney dysfunction, therefore, identifying specific biomarker to evaluate earlier podocyte injury is highly desirable. Podocyte-secreted angiopoietin-like-4 (Angptl4) mediates proteinuria in different types of podocytopathy. In the present study, we established an experimental minimal change disease (MCD) rat model, induced by adriamycin (ADR) and resulted in definite podocyte injury, to identify the dynamic changes in Angptl4 expression. We also investigated the direct effects of tacrolimus on Angptl4 and podocyte repair. We determined that the glomerular Angptl4 expression was rapidly upregulated and reached a peak earlier than desmin, an injured podocyte marker, in the ADR rats. Furthermore, this upregulation occurred prior to heavy proteinuria and was accompanied by increased urinary Angptl4. We observed that the Angptl4 upregulation occurred only when podocyte was mainly damaged since we didn't observe little Angptl4 upregulation in MsPGN patients. In addition, we observed the glomerular Angptl4 mainly located in injured podocytes rather than normal podocytes. Moreover, we found that tacrolimus treatment significantly promoted podocyte repair and reduced glomerular and urinary Angptl4 expression at an earlier stage with a significant serum Angptl4 upregulation. And similar results were confirmed in MCD patients. In conclusion, this study represents the first investigation to demonstrate that Angptl4 can predict podocyte injury at earlier stages in MCD and the identification of earlier podocyte injury biomarkers could facilitate the prompt diagnosis and treatment of patients with podocytopathy, as well as determination of the prognosis and treatment efficacy in these diseases.

  18. Reversion of Multi-drug Resistance by Nitidine Chloride on A2780 Taxol Cell%氯化两面针碱对人卵巢癌紫杉醇耐药细胞株A2780 Taxol细胞耐药性的逆转作用

    Institute of Scientific and Technical Information of China (English)

    冯燕英; 刘华钢; 梁燕; 张华君; 梁乔芳; 李俊威

    2015-01-01

    目的:研究氯化两而针碱(nitidine chloride,NC)对人卵巢癌紫杉醇耐药细胞株A2780 Taxol细胞耐药性的逆转作用及机制.方法:氯化两面针碱干预A2780 Taxol后,应用MTT比色法检测多柔比星(adriamycin,ADM),依托泊苷(etoposide,VP-16),羟基喜树碱(hydroxycamptothecin,HCPT)对A2780Taxol细胞的抑制率;实时荧光定量PCR检测不同给药组对多药耐药基因(MDR1 mRNA)表达的影响;HE染色法观察肿瘤细胞结构的改变;TUNEL法分析其对细胞凋亡的影响.结果:耐药细胞A2780 Taxol对ADM,VP-16,HCPT的耐药倍数分别为1.87,1.07,3.25;经氯化两面针碱干预后,降低了A2780Taxol细胞对抗肿瘤药ADM,VP-16,HCPT的IC50值,可下降A2780 Taxol细胞的多药耐药(MlDR1)基因的表达,HE染色可见NC给药组改变了A2780 Taxol细胞的形态结构,TUNEL染色凋亡细胞明显增多,凋亡指数为(58.03±1.46)%.结论:氯化两面针碱能有效逆转A2780 Taxol多药耐药性,具有良好的抗肿瘤药物多药耐药逆转作用.

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Development of multiple myeloma in a patient with chronic hepatitis C: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos; Sandor Fekete; Margit Horanyi; Simon Fischer; Margit E Abonyi

    2006-01-01

    An association between chronic hepatitis C virus (HCV)infection and essential mixed cryoglobulinaemia and nonHodgkin lymphoma (NHL) has been suggested. However,a causative role of HCV in these conditions has not been established. The authors report a case of a 50 year-old woman with chronic hepatitis C (CHC) who has been followed up since 1998 due to a high viral load, genotype 1b and moderately elevated liver function tests (LFTs).Laboratory data and liver biopsy revealed moderate activity (grade: 5/18, stage: 1/6). In April 1999, one-year interferon therapy was started. HCV-RNA became negative with normalization of LFTs. However, the patient relapsed during treatment. In September 2002, the patient was admitted for chronic back pain. A CT examination demonstrated degenerative changes. In March 2003,multiple myeloma was diagnosed (IgG-kappa, bone marrow biopsy: 50% plasma cell infiltration). MRI revealed a compression fracture of the 5th lumbar vertebral body and an abdominal mass in the right lower quadrant, infiltrating the canalis spinalis. Treatment with vincristine,adriamycin and dexamethasone (VAD) was started and bisphosphonate was administered regularly. In January 2004, after six cycles of VAD therapy, the multiple myeloma regressed. Thalidomide, as a second line treatment of refractory multiple myeloma (MM) was initiated,and followed by peginterferon-α2b and ribavirin against the HCV infection in June. In June 2005, LFTs returned to normal, while HCV-RNA was negative, demonstrating an end of treatment response. Although a pathogenic role of HCV infection in malignant lymphoproliferative disorders has not been established, NHL and possibly MM may develop in CHC patients, supporting a role of a complex follow-up in these patients.

  2. Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer

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    Ono M

    2013-10-01

    Full Text Available Mayu Ono, Tokiko Ito, Toshiharu Kanai, Koichi Murayama, Hiroshi Koyama, Kazuma Maeno, Yasuhiro Mochizuki, Asumi Iesato, Toru Hanamura, Toshihiro Okada, Takayuki Watanabe, Ken-ichi ItoDivision of Breast and Endocrine Surgery, Department of Surgery (II, Shinshu University School of Medicine, Matsumoto, JapanAbstract: Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient's entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual

  3. RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells

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    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.

  4. The value of radionuclide bone imaging on monitoring chemotherapeutic effects of multiple myeloma%核素骨显像在多发性骨髓瘤疗效评价中的应用

    Institute of Scientific and Technical Information of China (English)

    Yongli Bai; Shuyao Zuo; Chao Ma; Xiaoting Su

    2008-01-01

    Objective: To investigate the value of radionuclide whole-body bone imaging on monitoring chemotherapeutic effects for multiple myeloma (MM). Methods: Sixty patients were included. Twenty nine cases received CTD (thalidomide 100-200 mg/d; cyclophosphamide 200-300 mg/m2·d, 1-4 days, every 4 weeks; and dexamethasone 20-40 rag/d, 1-4 days, every 4 weeks); Thirty cases received VAD (vincristine 0.4 mg/d, 1-4 days, every 4 weeks; adriamycin 10 rag/d, 1-4 days, ev-ery 4 weeks; dexamethasone 40 mg/d, 1-4 days, every 4 weeks). Radionuclide bone imagings were performed in all patients before chemotherapy, six months, twelve months and eighteen months after chemotherapy. The correlation of chemotherapeutic effects between CTD and VAD were analyzed. Results: One hundred and seventy nine bone lesions were visualized by bone scintigraphy before CTD treatment. Eighteen months after CTD chemotherapy, it was observed by bone scintigraphy that 39/179 (21.78%) lesions disappeared, 112/179 (62.57%)improved, and 28/179 (15.64%) had no change. One hundred and ninety one bone lesions were showed by bone imaging before VAD treatment, 36/191 (18.84%) lesions disappeared, eighteen months after chemotherapy, 103/191 (53.92%) improved, and 52/191 (27.22%) had no change. The significant difference was observed in locations of MM induced bone lesions treated with CTD (H = 8.23, P < 0.05) and VAD (H = 11.18, P < 0.05). A significant chemotherapeutic sensitivity in detecting MM induced lesions in ribs was found compared with other bone lesions. The chemotherapeutic effect of CTD was statistically significant than that of VAD (U = 2.17, P < 0.05). Conclusion: Radionuclide whole-body bone imaging has great value in monitoring chemotherapeutic effects for MM.

  5. Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG).

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    Boku, Narikazu

    2011-12-01

    Initially, Gastrointestinal Study Group in Japan Clinical Oncology Group (GIOSG/JCOG) focused on gastric cancer. In 1980s, fluoropyrimidine, cisplatin and mitomycin C were key drugs. A randomized Phase II trial (JCOG8501) comparing futrafur plus mitomycin C and uracil plus futrafur and mitomycin C showed a higher response rate of uracil plus futrafur and mitomycin C than futrafur plus mitomycin C. From the results of two Phase II trials of etoposide, adriamycin and cisplatin, and cisplatin plus 5-fluorouracil, uracil plus futrafur and mitomycin C and cisplatin plus 5-fluorouracil were adopted for the test arms of the Phase III trial (JCOG9205) comparing with continuous infusion of 5-fluorouracil as a control arm. Neither cisplatin plus 5-fluorouracil nor uracil plus futrafur and mitomycin C showed a survival benefit over continuous infusion of 5-fluorouracil. In late 1990s, new agents, irinotecan and S-1, were developed for gastric cancer in Japan. GIOSG conducted a Phase III trial (JCOG9912) investigating superiority of irinotecan plus cisplatin and non-inferiority of monotherapy with S-1 compared with continuous infusion of 5-fluorouracil, and S-1 succeeded in showing non-inferiority. Then, SPIRITS trial showed a survival benefit of S-1 plus cisplatin over S-1, resulting in the establishment of a standard care for advanced gastric cancer in Japan. GIOSG have merged with Gastric Cancer Study Group as the Stomach Cancer Study Group (SCSG) from 2011. Recent progress in the development of new drugs has been remarkable. From the point of the roles shared with many other study groups for clinical trials, including registration trials of new drugs conducted by pharmaceutical companies, SCSG should recognize its role and conduct clinical trials with high quality for establishing new standard treatment.

  6. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

    Science.gov (United States)

    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. PMID:27347147

  7. 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.

  8. LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity.

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    Roberta Bertelli

    Full Text Available Immunosuppressive regulatory T cells (Tregs have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna and/or drug induced (Adriamycin nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg was given as single shot in C57BL/6, p2rx7⁻/⁻ and Foxp3EGFP; free IL-2 (18.000 U or, in alternative, IL-2 coupled with JES6-1 mAb (IL-2/anti-IL-2 were injected before LPS. Peripheral and tissue Tregs/total CD4+ cell ratio, urinary parameters and renal histology were evaluated for 15 days. IL-2 administration to wild type mice had no effect on peripheral Tregs number, whereas a significant increase was induced by the IL-2/anti-IL-2 immunocomplex after 5 days. Spleen and lymph nodes Tregs were comparably increased. In p2rx7⁻/⁻ mice, IL-2/anti-IL-2 treatment resulted in increase of peripheral Tregs but did not modify the spleen and lymph nodes quota. LPS induced comparable and transient proteinuria in both wild type and p2rx7⁻/⁻ mice. Proteinuria was inhibited by co-infusion of human IL-2, with reduction at each phase of the disease (24 -48 and 72 hours whereas IL-2/anti-IL-2 produced weaker effects. In all mice (wild type and p2rx7⁻/⁻ and irrespective of treatment (IL-2, IL-2/anti-IL-2, LPS was associated with progressive signs of renal pathologic involvement resulting in glomerulosclerosis. In conclusion, IL-2 plays a transient protective effect on proteinuria induced by LPS independent of circulating or tissue Tregs but does not modify the outcome of renal degenerative renal lesions.

  9. 带蒂大网膜包肾防治肾小球硬化的实验研究%The Effects of Pedicled Omental Transposition on Rats with Glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    董兴刚; 安增梅; 杨海春; 周江华; 殷祥雷; 顾建新

    2001-01-01

    To investigate the protective effects of pedicled omental transposition on the kidney with glomerulosclerosis.Uninephrectomized rats were divided into two groups.Normal rats were put in the blank control group,glomerulosclerosis rats by adriamycin were divided into glomerulosclerosis group and pedicled omental transposition group.Serum lipids,urea and urinary protein were assayed. Renal histological examination was also performed. Results showed that pedicled omental transposition could not only reduced the serum levels of total cholesterol and triglyceride, but also decrease the accumulation of extracellular matrix (P<0.05).Conclusions pedicled omental transposition has the effect of attenuating renal damage in rats with glomerulosclerosis.%为探讨带蒂大网膜包肾术防治肾小球硬化的作用。采用单侧肾切除加二次注射阿霉素制备的肾小球硬化动物模型,观察带蒂大网膜包肾对肾脏的作用。结果表明,带蒂大网膜包肾可降低血胆固醇、甘油三脂,尿蛋白排泄,肾小球球囊粘连减轻。血尿素氮有下降趋势。说明带蒂大网膜包肾术对肾小球硬化大鼠的肾脏损伤有保护作用。

  10. Antitumor activities of a new indolocarbazole substance, NB-506, and establishment of NB-506-resistant cell lines, SBC-3/NB.

    Science.gov (United States)

    Kanzawa, F; Nishio, K; Kubota, N; Saijo, N

    1995-07-01

    The novel anticancer glucosyl derivative of indolo-carbazole (NB-506), an inhibitor of DNA topoisomerase I, exhibited strong in vitro cytotoxicity against various human cancer cell lines. In order to elucidate its cytotoxic mechanisms, we established nine NB-506-resistant sublines with different resistance ratios from human small cell lung cancer cells (SBC-3/P) by stepwise and brief exposure (24 h) to NB-506. Among them, SBC-3/NB#9 was 454 times more resistant to NB-506 than the parent cell line. The SBC-3/NB#9 cells showed cross-resistance only to topoisomerase I inhibitors, such as 11,7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecia and 7-ethyl-10-hydroxy-camptothecin, and not to other anticancer drugs, such as vincristine, vinblastine, Adriamycin, etoposide, and teniposide. These results indicate that the difference on the effect of topoisomerase I was considered to be related to a resistance mechanism. The topoisomerase I activities of nuclear extracts eluted from SBC-3/NB#9 cells was only one-tenth of the parent cell activity. A Western blotting study indicated that this lower activity was due to a lower amount of DNA topoisomerase I. Furthermore, we found correlations between topoisomerase I activity and sensitivity to NB-506 in sublines with different degrees of resistance. Accumulation of 3H-labeled NB-506 by SBC-3/NB#9 cells was only one-fifth of that by the parent cells, whereas intracellular accumulation of 3H-labeled camptothecin by both cell lines did not differ. The reduction of accumulation was specific to NB-506, and this result may explain why the resistance ratio for NB-506 was higher than those for 11,7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-hydroxy-camptothecin.

  11. CCL21/CCR7 enhances the proliferation, migration, and invasion of human bladder cancer T24 cells.

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    Miao Mo

    Full Text Available To investigate the effects of CCL21/CCR7 on the proliferation, migration, and invasion of T24 cells and the possible associated mechanisms: expression of MMP-2 and MMP-9, and regulation of BCL-2 and BAX proteins.T24 cells received corresponding treatments including vehicle control, antibody (20 ng/mL CCR7 antibody and 50 ng/ml CCL21, and 50, 100, and 200 ng/ml CCL21. Proliferation was evaluated by MTT assay; cell migration and invasion were assayed using a transwell chamber. Cell apoptosis was induced by Adriamycin (ADM. The rate of cell apoptosis was examined by flow cytometry using annexin V-FITC/PI staining. Western-blot was used to analyze MMP-2 and MMP-9 and BCL-2 and BAX proteins.CCL21 promoted T24 cell proliferation in concentration-dependent manner with that 200 ng/mL induced the largest amount of proliferation. Significant differences of cell migration were found between CCL21treatment groups and the control group in both the migration and invasion studies (P < 0.001 for all. The expressions of MMP-2 and MMP-9 proteins were significantly increased after CCL21 treatment (p < 0.05 for all. Protein expression of Bcl-21 follows an ascending trend while the expression of Bax follows a descending trend as the concentration of CCL21 increases. No difference was found between the control group and antibody group for all assessments.CCL21/CCR7 promoted T24 cell proliferation and enhanced its migration and invasion via the increased expression of MMP-2 and MMP-9. CCL21/CCR7 had antiapoptotic activities on T24 cells via regulation of Bcl-2 and Bax proteins. CCL21/CCR7 may promote bladder cancer development and metastasis.

  12. Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines.

    Science.gov (United States)

    Yamamoto, Kimiyo N; Hirota, Kouji; Kono, Koichi; Takeda, Shunichi; Sakamuru, Srilatha; Xia, Menghang; Huang, Ruili; Austin, Christopher P; Witt, Kristine L; Tice, Raymond R

    2011-08-01

    Included among the quantitative high throughput screens (qHTS) conducted in support of the US Tox21 program are those being evaluated for the detection of genotoxic compounds. One such screen is based on the induction of increased cytotoxicity in seven isogenic chicken DT40 cell lines deficient in DNA repair pathways compared to the parental DNA repair-proficient cell line. To characterize the utility of this approach for detecting genotoxic compounds and identifying the type(s) of DNA damage induced, we evaluated nine of 42 compounds identified as positive for differential cytotoxicity in qHTS (actinomycin D, adriamycin, alachlor, benzotrichloride, diglycidyl resorcinol ether, lovastatin, melphalan, trans-1,4-dichloro-2-butene, tris(2,3-epoxypropyl)isocyanurate) and one non-cytotoxic genotoxic compound (2-aminothiamine) for (1) clastogenicity in mutant and wild-type cells; (2) the comparative induction of γH2AX positive foci by melphalan; (3) the extent to which a 72-hr exposure duration increased assay sensitivity or specificity; (4) the use of 10 additional DT40 DNA repair-deficient cell lines to better analyze the type(s) of DNA damage induced; and (5) the involvement of reactive oxygen species in the induction of DNA damage. All compounds but lovastatin and 2-aminothiamine were more clastogenic in at least one DNA repair-deficient cell line than the wild-type cells. The differential responses across the various DNA repair-deficient cell lines provided information on the type(s) of DNA damage induced. The results demonstrate the utility of this DT40 screen for detecting genotoxic compounds, for characterizing the nature of the DNA damage, and potentially for analyzing mechanisms of mutagenesis.

  13. Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

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    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.

  14. 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.

  15. Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine

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    Louie, K.G.; Behrens, B.C.; Kinsella, T.J.; Hamilton, T.C.; Grotzinger, K.R.; McKoy, W.M.; Winker, M.A.; Ozols, R.F.

    1985-05-01

    The optimum integration of chemotherapy and irradiation is of potential clinical significance in the treatment of ovarian cancer. A series of human ovarian cancer cell lines have been developed in which dose-response relationships to standard anticancer drugs have been determined, and the patterns of cross-resistance between these drugs and irradiation have been established. By stepwise incubation with drugs, sublines of A2780, a drug-sensitive cell line, have been made 100-fold, 10-fold, and 10-fold more resistant to Adriamycin (2780AD), melphalan (2780ME), and cisplatin (2780CP). Two additional cell lines, NIH:OVCAR-3nu(Ag+) and NIH:OVCAR-4(Ag+), were established from drug-refractory patients. 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) are all cross-resistant to irradiation, with DOS of 146, 187, 143, and 203, respectively. However, 2780AD remains sensitive to radiation, with a DO of 111, which is similar to that of A2780 (101). Glutathione (GSH) levels are elevated in 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) to 4.58, 6.13, 12.10, and 15.14 nmol/10(6) cells as compared to A2780, with 1.89 nmol/10(6) cells. However, the GSH level in 2780AD is only minimally higher than that in A2780 (2.94 nmol/10(6) cells). Buthionine sulfoximine, a specific inhibitor of GSH synthesis, significantly increases the radiation sensitivity of 2780ME (changing the DO from 143 to 95) and 2780CP to a lesser extent, suggesting that intracellular GSH levels may play an important role in the radiation response of certain neoplastic cells.

  16. 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.

  17. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Relationship between RFC gene expression and intracellular drug concentration in methotrexate-resistant osteosarcoma cells.

    Science.gov (United States)

    Wang, J J; Li, G J

    2014-07-24

    Osteosarcoma is a primary malignant tumor in adolescents, associated with high mortality and morbidity. The high-dose methotrexate (MTX) chemotherapy used to treat this disease may induce primary or secondary drug resistance, resulting in a reduced effect of comprehensive treatment. In this study, the relationship between reduced folate carrier (RFC) gene expression and intracellular drug concentration in MTX-resistant osteosarcoma cells (Saos-2) was investigated. MTX-resistant human osteosarcoma cells (Saos-2/MTX2.2, Saos-2/MTX4.4) were prepared. The sensitivities of Saos-2 (primary cells), Saos-2/MTX2.2, and Saos-2/MTX4.4 cells to MTX, diamminedichloroplatinum (DDP), ifosfamide (IFO), epirubicine (EPI), adriamycin (ADM), theprubicin (THP), and paclitaxel (PTX) were detected by MTT. The median inhibitory concentration (IC50) and resistance index were measured. Semi-quantitative RT-PCR was used to evaluate the expression of RFC gene in cells. The intracellular (3)H-MTX concentration was determined. Results showed that IC50 of Saos-2/MTX2.2 and Saos-2/MTX4.4 was 4.87 and 12.73 times that of Saos-2, respectively. Both Saos-2/MTX2.2 and Saos-2/MTX4.4 had resistance to IFO, ADM, EPI, THP, and PTX, but not DDP. Compared to Saos-2/MTX2.2 and Saos-2/MTX4.4, the expression of RFC mRNA in Saos-2 was significantly higher. The intracellular (3)H-MTX concentration reached a peak at 50 min. After 70 min, the concentration was maintained at a plateau. During this phase, the (3)H-MTX concentration in Saos-2 cells was 2.15 times higher than the concentration in Saos-2/MTX4.4 cells. The reduced RFC mRNA expression in PTX-resistant osteosarcoma cells may be related to the decrease in intracellular (3)H-MTX concentration.

  19. 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.

  20. 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.

  1. 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.

  2. Clinical evaluation of reduced MIBG uptake in the infero-posterior segments

    Energy Technology Data Exchange (ETDEWEB)

    Terada, Kouji [Kyoto Prefectural Univ. of Medicine (Japan)

    1999-07-01

    The quantitative assessment of the reduced uptake of {sup 123}I-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.)

  3. Phytochemical screening and antioxidant, antimitotic, and antiproliferative activities of Trichodesma indicum shoot

    Directory of Open Access Journals (Sweden)

    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.

  4. Genistein and cancer: current status, challenges, and future directions.

    Science.gov (United States)

    Spagnuolo, Carmela; Russo, Gian Luigi; Orhan, Ilkay Erdogan; Habtemariam, Solomon; Daglia, Maria; Sureda, Antoni; Nabavi, Seyed Fazel; Devi, Kasi Pandima; Loizzo, Monica Rosa; Tundis, Rosa; Nabavi, Seyed Mohammad

    2015-07-01

    Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.

  5. 异鼠李素抗癌活性研究%Research on the Antitumor Activity of Isorhamnetin

    Institute of Scientific and Technical Information of China (English)

    谭琪明; 胡丹

    2016-01-01

    The antitumor activity of isorhamnetin was studied. The human breast cancer cell line MCF7 treated with different concentrations of isorhamnetin were examined for cell inhibitory activity by using SRB assay and the human leukemia cell lines K562 and HL60 treated with different concentrations of isorhamnetin were examined for cell inhibitory activity by using MTT assay. The results showed that under the condition of different concentrations of isorhamnetin, the highest human breast cancer cell line MCF7 inhibition rate was (69.55±3.17)%, the lowest was (59.42±4.40)%. The human breast cancer cell line MCF7 inhibition rate of 0.3 μmol/mL adriamycin reached (76.08±3.32)%, there was no significant difference between it and 0.063μmol/mL isorhamnetin. And under the condition of different concentrations of isorhamnetin, the highest human leukemia cell line K562 inhibition rate was (100±4.12)%, the lowest was(9.84±1.14)%. The human leukemia cell line K562 inhibition rate of 10μmol/mL adriamycin reached (87.59±1.38)%, there was no significant difference between it and 0.633μmol/mL isorhamnetin. And under the condition of different concentrations of isorhamnetin, the highest human leukemia cell line HL60 inhibition rate was (100±6.89)%, the lowest was (12.50±1.41)%. The human leukemia cell line HL60 inhibition rate of 10μmol/mL adriamycin reached (94.20 ± 2.17)%, there was no significant difference between it and 0.633μmol/mL isorhamnetin. Isorhamnetin had a certain activity of antitumor.%为了研究沙棘中异鼠李素的抗癌活性,分别采用了 SRB 法测试不同浓度异鼠李素对人乳腺癌细胞株MCF-7细胞的抑制率以及MTT法测试不同浓度异鼠李素对人白血病细胞株K562和HL60的抑制率。结果为不同浓度异鼠李素对人乳腺癌细胞株MCF-7细胞的抑制率达(59.42±4.40)%~(69.55±3.17)%,其中0.063μmol/mL异鼠李素对人乳腺癌细胞株MCF-7细胞抑制率为(69.55±3.17)%,与0.3μmol/mL

  6. Atrial Function in Patients with Breast Cancer After Treatment with Anthracyclines

    Directory of Open Access Journals (Sweden)

    Yalin Tolga Yaylali

    Full Text Available Abstract Background: Atrial electromechanical delay (EMD is used to predict atrial fibrillation, measured by echocardiography. Objectives: The aim of this study was to assess atrial EMD and mechanical function after anthracycline-containing chemotherapy. Methods: Fifty-three patients with breast cancer (48 ± 8 years old who received 240 mg/m2of Adriamycin, 2400 mg/m2 of cyclophosphamide, and 960 mg/m2 of paclitaxel were included in this retrospective study, as were 42 healthy subjects (47 ± 9 years old. Echocardiographic measurements were performed 11 ± 7 months (median 9 months after treatment with anthracyclines. Results: Left intra-atrial EMD (11.4 ± 6.0 vs. 8.1 ± 4.9, p=0.008 and inter-atrial EMD (19.7 ± 7.4 vs. 14.7 ± 6.5, p=0.001 were prolonged; LA passive emptying volume and fraction were decreased (p=0.0001 and p=0.0001; LA active emptying volume and fraction were increased (p=0.0001 and p=0.0001; Mitral A velocity (0.8 ± 0.2 vs. 0.6 ± 0.2, p=0.0001 and mitral E-wave deceleration time (201.2 ± 35.6 vs. 163.7 ± 21.8, p=0.0001 were increased; Mitral E/A ratio (1.0 ± 0.3 vs. 1.3 ± 0.3, p=0.0001 and mitral Em (0.09 ± 0.03 vs. 0.11 ± 0.03, p=0.001 were decreased; Mitral Am (0.11 ± 0.02 vs. 0.09 ± 0.02, p=0.0001 and mitral E/Em ratio (8.8 ± 3.2 vs. 7.6 ± 2.6, p=0.017 were increased in the patients. Conclusions: In patients with breast cancer after anthracycline therapy: Left intra-atrial, inter-atrial electromechanical intervals were prolonged. Diastolic function was impaired. Impaired left ventricular relaxation and left atrial electrical conduction could be contributing to the development of atrial arrhythmias.

  7. The study on the suppression effect of nicardipine on the proliferation of drug-resistant liver cancer cells%尼卡地平抑制肝癌耐药细胞增殖的研究

    Institute of Scientific and Technical Information of China (English)

    陈贤鸿; 王炳芳; 陈锡美

    2001-01-01

    目的探讨尼卡地平抑制肝癌耐药细胞增殖的机制。方法采用同位素掺入法研究细胞的增殖,荧光分光光度法测定细胞内抗癌药物浓度。结果单独应用尼卡地平(NIC)对耐药肝癌细胞BEL-7402/ADR有不同程度的抑制作用;而对细胞增殖基本无影响的2.5μg*ml-1浓度的NIC与阿霉素(ADR)合用时,半数抑制量(IC50)较单独用ADR时明显降低(P<0.05);与5.0μg*ml-1的NIC合用时,其IC50较单独用ADR降低更显著(P<0.01)。NIC可显著增加细胞内的抗癌药浓度(P<0.05~0.01)。结论 NIC降低ADR的IC50,增加抗癌药的细胞毒性,可能与其拮抗P170糖蛋白有关。%Objective To investigate the mechanism through which nicardipine (NIC) suppress the proliferation of drug-resistant liver cancer cells.Method Cellular proliferation were studied by isotope labeling technique,and the concentrations of intracellular anticancer drugs were measured by fluorospectrophotometry.Results Nicardipine alone exhibited different degree of suppressive effects on drug-resistant liver cancer cells,BEL-7402/ADR.While adriamycin(ADR) in combination with NIC at the concentration of 2.5μg*ml-1,IC50 were significantly reduced(P<0.05) when compared with ADR alone.When the concentration of rosed to NIC 5.0μg*ml-1,IC50 were more significantly reduced(P<0.01).The results also showed that NIC evidently increased the concentration of intracellular anticancer drugs.Conclusion NIC can both reduce the IC50 of ADR and increase the cytotoxicitry of anticancer drugs.This action may be related to its antagonizing P170 glocoprotein.

  8. 滋肾活血方在抗肾纤维化中对HA、LN、TGF-β1干预作用的实验研究%An experimental study of intervention effect of the Zishen Huoxue recipe against HA, LN, TGF-β1 in anti-renal fibrosis

    Institute of Scientific and Technical Information of China (English)

    曹秋彩

    2013-01-01

      目的:探讨滋肾活血方对慢性肾病肾纤维化的防治作用及机制。方法:采用右侧肾切除加重复尾静脉注射阿霉素制备肾纤维化大鼠模型[1]。设滋肾活血方治疗组、卡托普利对照组、模型组、空白组。8周后观察各组大鼠24h蛋白定量、血清尿素氮(Bun)、肌肝(Scr)、透明质酸(HA)、层粘蛋白(LN)和肾组织中转化生长因子β1(TGF-β1)表达的变化。结果:滋肾活血方能够减少阿霉素肾纤维化大鼠尿蛋白的排泄,降低血清Bun、Scr、HA、LN的含量,抑制肾组织中TGF-β1的过度表达。结论:滋肾活血方能够延缓肾纤维化的进程,具有保护肾功能的作用。%  Objective:To investigate the effect of Zishen Huoxue recipe anti-chronicity nephropathy renal fibrosis preventive and therapeutic effect and mechanism. Methods:According to reference documents[1], we reproduced the rat model of adriamycin nephrosis by having right nephrectomy adding to injecting repeatedly ADR through the vein of tail. The rats were divided into four groups for the bland contral group, the Zishen Huoxue recipe group, the captopril group and the model group. We observe quantity of 24h urinary protein excretion, blood urea nitrogen and creatinine, HA , laminin and tranforming growth factorβ1 in kidney tissues after 8 weeks. Results:The Zishen Huoxue recipe can decrease quantity of 24h urinary protein excretion, degrade blood serum hyaluronic acid and laminin contents, depress tranforming growth factorβ1 over expression in kidney tissues. Conclusion:Zishen Huoxue recipe can prevent process of the renal fibrosis, to have preserve effect of the renal function.

  9. Perspectives on research in gynecologic oncology.

    Science.gov (United States)

    DeVita, V T; Wasserman, T H; Young, R C; Carter, S K

    1976-07-01

    role as postoperative adjuncts in patients who have resectable tumor but a definite high risk of recurrence. Systemic chemotherapy has been rarely used with any consistency against this tumor but, even so, some chemotherapeutic leads, such as the use of adriamycin, are worthy of exploration. The absence of useful information on systemic treatment of gynecologic malignancies can be traced to the excessive rigid compartmentalization of medical practice. Only recently have investigators of all persuasions begun to explore and exploit some of the therapeutic opportunities, which have been available for some time.

  10. 补骨脂素对MCF-7/ADR耐药细胞内ADR及Ca2+浓度的影响%Effects of Psoralen on ADR Multidrug Resistance and Ca2+ Concentration in MCF-7/ADR Cells

    Institute of Scientific and Technical Information of China (English)

    蔡天革; 蔡宇; 余绍蕾; 冯笑珍

    2007-01-01

    Objective To research the reversal effects of psoralen on multidrug resistant action and its influence on intracellular Ca2+ concentration in MCF-7/ADR cells and to explore its possible mechanisms of reversing multidrug resistance (MDR). Methods The inhibitory effects of psoralen on the viability of MCF-7/ADR cells were determined with MTT assay, intracellular adriamycin (ADR) concentration was assayed with HPLC and the intracellular Ca2+ concentrations in different incubative duration were detected with confocal microscope. Results Psoralen from 1 to 20 μmol/L reduced the value of IC50 of ADR in MCF-7/ADR cells, enhanced accumulation of ADR and influenced Ca2+ concentration with a negative correlation in different duration (24 h, 48 h and 96 h). Conclusion Psoralen can reverse MDR in MCF-7/ADR cells and its mechanism may be related to the increase of the intracellular accumulation of ADR by enhancing the intracellular Ca2+ concentration.%目的 研究补骨脂素对MCF-7/ADR耐药细胞逆转作用及对耐药细胞内Ca2+浓度影响,探讨其可能作用机制.方法 采用MTT法测定补骨脂素对细胞增殖抑制作用,高效液相色谱法检测细胞内ADR的浓度,激光共聚焦显微镜测定细胞内不同时段的Ca2+浓度.结果 补骨脂素在1~20 μmol/L浓度下能不同程度降低ADR对MCF-7/ADR细胞的IC50,并不同程度提高细胞内ADR浓度;1~20 μmol/L补骨脂素在不同作用时段(24、48、96 h)对MCF-7/ADR细胞内Ca2+浓度与作用时间呈负相关.结论 补骨脂素能逆转MCF-7/ADR细胞的MDR,其作用机制与影响耐药细胞内Ca2+浓度,故而增加细胞内ADR浓度有关.

  11. Calcium Phosphate Cement for Drug Deliver Applications%磷酸钙骨水泥载药研究

    Institute of Scientific and Technical Information of China (English)

    张海燕; 邬伟魁; 宋伟; 李芳; 芦乾; 贺娅; 杨明

    2012-01-01

    This study investigated the applications of calcium phosphate cement ( CPC ) as drug deliver system. There is strong evidence that calcium phosphate cement is a nice drug deliver vector. Due to its unique properties, much attention has paied to CPC for drug deliver applications in both areas of research and application. In recent decades, different drugs have been loaded in CPC, including antibiotic ( tobramycin, gentamicin and clindamycin) , anti-tumor drugs (adriamycin, mitomycin, vincristine) and cell factors (bone morphogenetic protein and fibrin glue). Particularly, traditional Chinese medicines ( astraglycan, Xiangdan injection, Danhong injection, Danshen injection) used in the drug delivery system were summarized to provide the reference for the further improvement of herbal remedies loaded in CPC as a drug delivery system to treat bone disease.%对磷酸钙骨水泥(calcium phosphate cement,CPC)载药的国内外研究进行文献整理与分析.研究表明,CPC是一种优良的骨科药物载体,是近年国内外生物医学、材料学和药学领域共同的研究焦点.介绍了CPC载药系统所负载的不同药物,包括抗生素(如妥布霉素、庆大霉素和克林霉素等)、抗肿瘤药物(如阿霉素、丝裂霉素、长春新碱和5F-尿嘧啶等)和细胞因子(如骨形态发生蛋白和纤维蛋白胶等);讨论了中药(如黄芪多糖、香丹注射液、丹红注射液和复方丹参注射液等)在骨水泥载药中的应用研究现状,认为中药有望应用于CPC局部给药的临床研究,但目前相关安全性研究较少,有待加强.

  12. Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM-PLGA microspheres for bone cancer treatment.

    Science.gov (United States)

    Rong, Zi-Jie; Yang, Lian-Jun; Cai, Bao-Ta; Zhu, Li-Xin; Cao, Yan-Lin; Wu, Guo-Feng; Zhang, Zan-Jie

    2016-05-01

    To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic

  13. 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

  14. Protective Effects of Blocking Renin-Angiotensin System on the Progression of Renal Injury in Glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    Zequan Ji; Cuiwen Huang; Chengjie Liang; Bo Chen; Shengqiang Chen; Weiwen Sun

    2005-01-01

    To investigate the protective effects of blocking rennin-angiotensin system (RAS) on the progression of renal injury in glomerulosclerosis, a glomerulosclerosis model was made for SD rats by unilateral nephrectomy and being injected with Adriamycin into caudal vein. The rats with glomerulosclerosis were randomly divided as ten pergroup into those without further treatment (group D) and those treated with Benazepril (group DB), Losartan (group DL), or sham-operation (group C), respectively. After 6 weeks of administration of Benazepril or Losartan,the mRNA expressions of TGF-β1, Col Ⅳ, Fn, ET-1 and iNOS in renal cortex were measured by RT-PCR. Besides,the expressions of TGF-β1, ET-1 and iNOS at protein level were detected by Western blotting and the concentrations of Col Ⅳ and Fn were analyzed with immunohistochemistry respectively. Results showed that the rats in group D appeared as obvious proteinuria, hypoalbuminemia and hypercholesterolemia, which had a significant difference compared with group C (p<0.05), and most of their mesangiums were detected with cellular proliferation and significant increasing for extracellular matrix. Renal cortex TGF-β1, Col Ⅳ, Fn, ET-1 and iNOS in rats of group D were increased by 3.59, 2.57, 2.21, 2.58 and 3.28 times at mRNA level, and by 2.60, 1.40, 0.75, 1.83 and 2.15 times at protein level, respectively, compared with group C. When the animals were treated with Benazepril (group DB) or Losartan (group DL), however, the biochemical and pathological damages were significantly recovered, and protein expressions of TGF-β, Col Ⅳ, Fn, ET-1 and iNOS were also significantly diminished (p<0.05). This study suggested that blocking RAS using Benazepril or Losartan can have protective effects on the renal injury in glomerulosclerosis by down-regulating the expressions of TGF-β1, Col Ⅳ, Fn, ET-1 and iNOS. Cellular & Molecular Immunology. 2005;2(2):150-154.

  15. Protective Effects of Blocking Renin-Angiotensin System on the Progression of Renal Injury in Glomerulosclerosis

    Institute of Scientific and Technical Information of China (English)

    ZequanJi; CuiwenHuang; ChengjieLiang; BoChen; ShengqiangChen; WeiwenSun

    2005-01-01

    To investigate the protective effects of blocking rennin-angiotensin system (RAS) on the progression of renal injury in glomerulosclerosis, a glomerulosclerosis model was made for SD rats by unilateral nephrectomy and being injected with Adriamycin into caudal vein. The rats with glomerulosclerosis were randomly divided as ten per group into those without further treatment (group D) and those treated with Benazepril (group DB), Losartan (group DL), or sham-operation (group C), respectively. After 6 weeks of administration of Benazepril or Losartan, the mRNA expressions of TGF-β1, Col IV, Fn, ET-1 and iNOS in renal cortex were measured by RT-PCR. Besides, the expressions of TGF-β1, ET-1 and iNOS at protein level were detected by Western blotting and the concentrations of Col IV and Fn were analyzed with immunohistochemistry respectively. Results showed that the rats in group D appeared as obvious proteinuria, hypoalbuminemia and hypercholesterolemia, which had a significant difference compared with group C (p < 0.05), and most of their mesangiums were detected with cellular proliferation and significant increasing for extracellular matrix. Renal cortex TGF-β1, Col IV, Fn, ET-1 and iNOS in rats of group D were increased by 3.59, 2.57, 2.21, 2.58 and 3.28 times at mRNA level, and by 2.60, 1.40, 0.75, 1.83 and 2.15 times at protein level, respectively, compared with group C. When the animals were treated with Benazepril (group DB) or Losartan (group DL), however, the biochemical and pathological damages were significantly recovered, and protein expressions of TGF-β1, Col IV, Fn, ET-1 and iNOS were also significantly diminished (p < 0.05). This study suggested that blocking RAS using Benazepril or Losartan can have protective effects on the renal injury in glomerulosclerosis by down-regulating the expressions of TGF-β1, Col IV, Fn, ET-1 and iNOS. Cellular & Molecular Immunology. 2005;2(2):150-154.

  16. EFFECT OF HIGH—LIPID DIET ON GLOMERULAR MESANGIAL MATRIX IN ADRIAMYCIN—INDUCED NEPHROTIC RATS

    Institute of Scientific and Technical Information of China (English)

    宋红梅; 李学旺; 等

    2002-01-01

    Objective:To determine the effect of hypercholesterolemia induced by a high-lipid diet on glomerulosclerosis.Methods:Twenty nephrotic syndrome (NS) Wistar rats administrated adriamycin(ADR) with a single intravenous dose of 5mg/kg body weight,were divided into the standard and high-lipid chow groups.Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as control.Urinary protein excretion and serum cholesterol were assayed;image analysis and techniques of pathology,immunohistochemistry,and molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrices in different groups.Results:The total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS[(2.2±0.3)g/L vs.(0.9±0.1)g/L,P<0.01] and NS[(9.5±0.2)g/L vs.(2.3±0.3)g/L,p<0.01].The urinary protein excretion was significantly higher in the high-lipid diet rats than in standard chow rats[(76.2±24.2)mg/24h vs.(44.8±13.6)mg/24h,P<0.05]in NS rats.Although increases in the mesangial matrix and mesangial cells were observed in rats with high-lipid diet in both NS and non-NS group,more obvious pathological changes were found in NS group,such as lipid deposits and foam cell formation in mesangial areas,and progressing to focal and segmental glomerulosclerosis in someglomeruli.Theimmunohistochemical assay showed that the production of 3 major components (collagen IV,fibronectin,and laminin)was increased in NS group,especially in the rats with high-lipid chow.The increased expression of laminin mRNA was also detected with slot blotting in bloth NS and non-NS rats with high-lipid chow,and it was more obvious in the rats with NS.Conclusion:Our findings indicated that diet-induced hyperlipidemia can lead to over-production of mesangial matrix components,and further aggravate glomerulosclerosis in ADR-induced nephrosis.

  17. A unique carrier for delivery of therapeutic compounds beyond the blood-brain barrier.

    Directory of Open Access Journals (Sweden)

    Delara Karkan

    Full Text Available BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin, across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX or adriamycin (ADR and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders

  18. Therapeutic efifcacy and bone marrow protection of the mdr1 gene and over-dose chemotherapy with doxorubicin for rabbits with VX2 hepatocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yi Wang; Xian-Qing Jin; Shan Wang; Qiao Wang; Qing Luo; Xiao-Ji Luo

    2006-01-01

    BACKGROUND: Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efifcacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits. METHODS: The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efifcacy of over-dose chemotherapy were observed. RESULTS:The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efifciency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26±1.03)×104/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00±46.75 d) of the rabbits was extended (P CONCLUSIONS:The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be

  19. Quercetin-loaded PEG-PE micelles reverse drug resistance of MCF-7 ADRr human breast cancer cells%载有槲皮素的PEG-PE胶束对乳腺癌细胞耐药性的逆转效应

    Institute of Scientific and Technical Information of China (English)

    吴金花; 段金虹; 许海燕; 杨先达

    2015-01-01

    Objective To explore whether quercetin-loaded PEG-PE micelles(M-Q) can synergize the growth-in-hibitory activity of adriamycin prepared ( ADR) by reversing the drug resistance of MCF-7 ADRr breast cancer cells in vitro.Methods M-Q was prepared by adding saline to lipid film containing quercetin and PEG-PE.The size of M-Q was characterized by dynamic light scattering ( DLS) .The inhibition of MCF-7 ADRr cells was evaluated by MTS assay after incubation with M-Q and ADR.Results The incorporation efficiency of quercetin by the micelles was above 74%.The average size of M-Q was 11.11 nm.Compared with the quercetin dissolved in ethanol , M-Q more effectively reversed the drug resistance of MCF-7 ADRr cells in vitro.Conclusions PEG-PE micelles may potentially deliver quercetin to cancer cells for reversal of drug resistance .%目的:探索载有槲皮素的PEG-PE聚合物胶束( M-Q)能否在体外逆转耐阿霉素人乳腺癌细胞( MCF-7 ADRr)的耐药性。方法将PEG-PE聚合物与槲皮素混合制备脂膜,加0.9%氯化钠注射液形成胶束,用动态光散射粒径仪表征其尺寸分布,并将其和阿霉素与MCF-7 ADRr细胞共孵育72 h,用MTS方法检测对肿瘤细胞的杀伤率。结果PEG-PE聚合物胶束能有效运载槲皮素,其包封率高达74%以上,平均粒径为11.11 nm左右,与游离槲皮素相比, M-Q能在体外更大程度地逆转MCF-7 ADRr细胞对于阿霉素的耐药性( P<0.05),且PEG-PE胶束自身对靶细胞无明显杀伤作用。结论载有槲皮素的PEG-PE胶束在逆转肿瘤耐药性方面具有应用潜能。

  20. ent-贝壳杉烯糖酯类衍生物的合成及其抗肿瘤活性的研究%Glycosylation of ent-kaurene derivatives and an evaluation of their cytotoxic activities

    Institute of Scientific and Technical Information of China (English)

    邹敏; 余双双; 王可; 张大永; 吴晓明; 华维一

    2013-01-01

    AIM:To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety.METHODS:All of the key intermediates were synthesized from stevioside,and the target compounds were obtained through glycosylation of the 4-carboxyl group.The cytotoxicity of the target compounds against six human cancer cell lines,HepG2,Bel-7402,A549,U251,MCF-7 and MDA-MB-231,were evaluated by the MTT assay.RESULTS:Compound 1b was more effective than the positive control adriamycin against the HepG2,Bel-7402,A549,MCF-7,and MDA-MB-231 cell lines with IC50 values of 0.12,0.91,0.35,0.08,and 0.07 μmol.L 1,respectively.Moreover,compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line (IC50,0.01 μmol·L-1).CONCLUSION:Compounds 1b and 3c could be considered as potential anticancer candidates for further study.%目的:对含有exo-亚甲基环戊酮或α-亚甲基内酯药效团的ent-贝壳杉烯类化合物进行结构修饰,以改善其活性及水溶性.方法:以甜菊苷为原料,在4位羧基接入单糖而得到目标化合物,并使用MTT法对目标化合物进行抗肿瘤活性测试.结果:化合物1b对细胞株HepG2,Bel-7402,A549,MCF-7,MDA-MB-231均表现出了较好的抑制活性,IC50分别为0.12,0.91,0.35,0.08,0.07 μmol.L-1.另外,化合物3c对HepG2(IC50=0.01 μmol·L-1)具有较强的抑制作用.结论:化合物1b和3c可以作为潜在的抗肿瘤化合物进行深入研究.

  1. Feasibility of organ preservation in muscle-invasive transitional cell carcinoma bladder: A single institutional approach

    Directory of Open Access Journals (Sweden)

    Chhaya Roy

    2015-01-01

    Full Text Available Background: Trimodality treatment initial transurethral resection of the bladder tumor [TURBT] followed by concurrent chemotherapy and radiation and organ preservation have been gradually replacing the radical cystectomy in muscle-invasive transitional cell carcinoma (TCC of bladder. Aims: The aims of this study is to determine the clinical effectiveness, safety and protocol completion rate of trimodality treatment in muscle-invasive TCC of the bladder. Settings and Design: Prospective randomized and open-labeled study. Subjects and Methods: Patients with TCC of bladder, American Joint Committee on Cancer tumor node metastasis (TNM Bladder Cancer Staging (2002 T2-3, N0, M0. Were underwent TURBT followed by three cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin regimen. The patients were then randomized to receive either concurrent cisplatin 75 mg/m 2 in week 1 and 4 (arm-A or no cisplatin (arm-B along with external beam radiation therapy (EBRT 45 Gy, in 25 fractions over 5 weeks. 4 weeks after completion of the initial phase of treatment, all patients were re-evaluated with TURBT. Those with complete remission (CR received additional 15 Gy of EBRT in 8 fractions, while patients with residual disease were recommended for immediate radical cystectomy. All the patients of arm-B received boost dose of 15 Gy of EBRT. Statistical Analysis Used: The major statistical endpoints of this study were the CR rate at 8 weeks post-concurrent chemoradiotherapy (CCRT and only radiotherapy. Statistical significance was accepted at the P < 0.05 (two-sided level. Statistical analysis was performed entirely using the Statistical Package for the Social Sciences for Windows, version 17 (SPSS Inc., Chicago, IL, U.S.A.. Results: 8 weeks after completion of treatment 13/16 (81% patients were in CR in CCRT arm (arm-A compare to 6/15 (40% patients receiving radiation only (arm-B. Conclusions: Patients, after TURBT receiving CCRT

  2. In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Gang; He, Yunfeng; Wu, Xiaohou; Zhang, Yao [Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China); Luo, Chunli [Department of Laboratory Medicine, Chongqing Medical University, Chongqing (China); Jing, Peng [Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2012-07-13

    Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer. Key words: Single-walled carbon nanotubes; Bladder cancer; Drug vehicle; THP; Intravesical chemotherapy.

  3. The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

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    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

  4. Single cell cytometry of protein function in RNAi treated cells and in native populations

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    Hill Andrew

    2008-08-01

    Full Text Available Abstract Background High Content Screening has been shown to improve results of RNAi and other perturbations, however significant intra-sample heterogeneity is common and can complicate some analyses. Single cell cytometry can extract important information from subpopulations within these samples. Such approaches are important for immune cells analyzed by flow cytometry, but have not been broadly available for adherent cells that are critical to the study of solid-tumor cancers and other disease models. Results We have directly quantitated the effect of resolving RNAi treatments at the single cell level in experimental systems for both exogenous and endogenous targets. Analyzing the effect of an siRNA that targets GFP at the single cell level permits a stronger measure of the absolute function of the siRNA by gating to eliminate background levels of GFP intensities. Extending these methods to endogenous proteins, we have shown that well-level results of the knockdown of PTEN results in an increase in phospho-S6 levels, but at the single cell level, the correlation reveals the role of other inputs into the pathway. In a third example, reduction of STAT3 levels by siRNA causes an accumulation of cells in the G1 phase of the cell cycle, but does not induce apoptosis or necrosis when compared to control cells that express the same levels of STAT3. In a final example, the effect of reduced p53 levels on increased adriamycin sensitivity for colon carcinoma cells was demonstrated at the whole-well level using siRNA knockdown and in control and untreated cells at the single cell level. Conclusion We find that single cell analysis methods are generally applicable to a wide range of experiments in adherent cells using technology that is becoming increasingly available to most laboratories. It is well-suited to emerging models of signaling dysfunction, such as oncogene addition and oncogenic shock. Single cell cytometry can demonstrate effects on cell

  5. A possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma

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    Svozílková Petra

    2013-01-01

    Full Text Available Abstract Purpose To present a possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma. Case presentation A 47-year-old woman presented with decreased visual acuity associated with white retinal lesions in both eyes. A history of pneumonia of unknown aetiology closely preceded the deterioration of vision. Five years previously the patient was diagnosed with follicular non-Hodgkin’s lymphoma. She was treated with a chemotherapy regimen comprised of cyclophosphamide, adriamycin, vincristin, and prednisone with later addition of the anti-CD20 antibody rituximab. She experienced a relapse 19 months later with involvement of the retroperitoneal lymph nodes, and commenced treatment with rituximab and 90Y-ibritumomab tiuxetan. A second relapse occurred 22 months after radioimmunotherapy and was treated with a combination of fludarabine, cyclophosphamide, and mitoxantrone followed by rituximab. The patient experienced no further relapses until the current presentation (April, 2010. Pars plana vitrectomy with vitreous fluid analysis was performed in the right eye. PCR testing confirmed the presence of cytomegalovirus in the vitreous. Atypical lymphoid elements, highly suspicious of malignancy were also found on cytologic examination. Intravenous foscarnet was administered continually for three weeks, followed by oral valganciclovir given in a dose of 900 mg twice per day. In addition, the rituximab therapy continued at three monthly intervals. Nevertheless, cessation of foscarnet therapy was followed by a recurrence of retinitis on three separate occasions during a 3-month period instigating its reinduction to the treatment regime after each recurrence. Conclusions Cytomegalovirus retinitis is an opportunistic infection found in AIDS patients as well as in bone marrow and solid organ transplant recipients being treated with systemic immunosuppressive drugs. This case presents a less

  6. In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

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    Gang Chen

    2012-08-01

    Full Text Available Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP. We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12, macroscopic hematuria (N = 1, and vomiting (N = 7 were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42% in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45% and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%. The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.

  7. In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer.

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    Chen, Gang; He, Yunfeng; Wu, Xiaohou; Zhang, Yao; Luo, Chunli; Jing, Peng

    2012-08-01

    Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.

  8. Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1

    Institute of Scientific and Technical Information of China (English)

    CHEN Yong-bing; XIE Jian-guo; YANG Jia-yin; YAN Lü-nan; YAN Mao-lin; GONG Jian-ping; XIA Ren-pin; LIU Li-xin; LI Ning; LU Shi-chun; ZHANG Jing-guang; ZENG Dao-bing

    2007-01-01

    Background The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1.Methods The 4.5-kb mdr1 cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCI-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated.Results The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed.The PCR analysis showed that the specific fragment of mdr1 cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7±7.9)% and (12.28±2.09)%, respectively, compared with (16.9±3.2)% and (3.07±1.06)% in HepG2 cells.In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours.Conclusion The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the

  9. Cross-linked polyethylenimine–tripolyphosphate nanoparticles for gene delivery

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    Huang XZ

    2014-10-01

    Full Text Available Xianzhang Huang,1 Sujing Shen,2 Zhanfeng Zhang,1 Junhua Zhuang1 1Department of Laboratory Science, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 2Department of Laboratory Science, Guangdong Second Provincial Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China Abstract: The high transfection efficiency of polyethylenimine (PEI makes it an attractive potential nonviral genetic vector for gene delivery and therapy. However, the highly positive charge of PEI leads to cytotoxicity and limits its application. To reduce the cytotoxicity of PEI, we prepared anion-enriched nanoparticles that combined PEI with tripolyphosphate (TPP. We then characterized the PEI-TPP nanoparticles in terms of size, zeta potential, and Fourier-transform infrared (FTIR spectra, and assessed their transfection efficiency, cytotoxicity, and ability to resist deoxyribonuclease (DNase I digestion. The cellular uptake of PEI-TPP with phosphorylated internal ribosome entry site–enhanced green fluorescent protein C1 or FAM (fluorouracil, Adriamycin [doxorubicin] and mitomycin-labeled small interfering ribonucleic acids (siRNAs was monitored by fluorescence microscopy and confocal laser microscopy. The efficiency of transfected delivery of plasmid deoxyribonucleic acid (DNA and siRNA in vitro was 1.11- to 4.20-fold higher with the PEI-TPP particles (7.6% cross-linked than with the PEI, at all N:P ratios (nitrogen in PEI to phosphorus in DNA tested. The cell viability of different cell lines was more than 90% at the chosen N:P ratios of PEI-TPP/DNA complexes. Moreover, PEI-TPP nanoparticles resisted digestion by DNase I for more than 2 hours. The time-dependent absorption experiment showed that 7.6% of cross-linked PEI-TPP particles were internalized by 293T cells within 1 hour. In summary, PEI-TPP nanoparticles effectively transfected cells while conferring little or no toxicity, and thus have potential application in gene

  10. Cell cycle inhibition therapy that targets stathmin in in vitro and in vivo models of breast cancer.

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    Miceli, C; Tejada, A; Castaneda, A; Mistry, S J

    2013-05-01

    Stathmin is the founding member of a family of microtubule-destabilizing proteins that have a critical role in the regulation of mitosis. Stathmin is expressed at high levels in breast cancer and its overexpression is linked to disease progression. Although there is a large body of evidence to support a role for stathmin in breast cancer progression, the validity of stathmin as a viable therapeutic target for breast cancer has not been investigated. Here, we used a bicistronic adenoviral vector that co-expresses green fluorescent protein and a ribozyme that targets stathmin messenger RNA in preclinical breast cancer models with different estrogen receptor (ER) status. We examined the effects of anti-stathmin ribozyme on the malignant phenotype of breast cancer cells in vitro and in xenograft models in vivo both as a single agent and in combination with chemotherapeutic agents. Adenovirus-mediated gene transfer of anti-stathmin ribozyme resulted in a dose-dependent inhibition of proliferation and clonogenicity associated with a G2/M arrest and increase in apoptosis in both ER-positive and ER-negative breast cancer cell lines. This inhibition was markedly enhanced when stathmin-inhibited breast cancer cells were exposed to low concentrations of taxol, which resulted in virtually complete loss of the malignant phenotype. Interestingly, breast cancer xenografts treated with low doses of anti-stathmin therapy and taxol showed regression in a majority of tumors, while some tumors stopped growing completely. In contrast, combination of anti-stathmin ribozyme and adriamycin resulted in only a modest inhibition of growth in vitro and in breast cancer xenografts in vivo. Although inhibition of tumor growth was observed in both the combination treatment groups compared with groups treated with single agent alone, combination of anti-stathmin therapy and taxol had a more profound inhibition of tumorigenicity, as both agents target the microtubule pathway. Clinically, these

  11. An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer.

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    Kelly H Salter

    Full Text Available A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective.Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%. When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06. Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8% of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04, representing a viable alternative therapy.Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding micro

  12. Posttreatment PET/CT Rather Than Interim PET/CT Using Deauville Criteria Predicts Outcome in Pediatric Hodgkin Lymphoma: A Prospective Study Comparing PET/CT with Conventional Imaging.

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    Bakhshi, Sameer; Bhethanabhotla, Sainath; Kumar, Rakesh; Agarwal, Krishankant; Sharma, Punit; Thulkar, Sanjay; Malhotra, Arun; Dhawan, Deepa; Vishnubhatla, Sreenivas

    2017-04-01

    Data about the significance of (18)F-FDG PET at interim assessment and end of treatment in pediatric Hodgkin lymphoma (HL) are limited. Methods: Patients (≤18 y) with HL were prospectively evaluated with contrast-enhanced CT (CECT) and PET combined with low-dose CT (PET/CT) at baseline, after 2 cycles of chemotherapy, and after completion of treatment. Revised International Working Group (RIW) criteria and Deauville 5 point-scale for response assessment by PET/CT were used. All patients received doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine chemotherapy along with involved-field radiotherapy (25 Gy) for early stage (IA, IB, and IIA) and advanced stage (IIB-IV) with bulky disease. Results: Of the 57 enrolled patients, median follow-up was 81.6 mo (range, 11-97.5 mo). Treatment decisions were based on CECT. At baseline, PET/CT versus CECT identified 67 more disease sites; 23 patients (40.3%) were upstaged and of them in 9 patients (39%) upstaging would have affected treatment decision; notably none of these patients relapsed. The specificity of interim PET/CT based on RIW criteria (61.5%) and Deauville criteria (91.4%) for predicting relapse was higher than CECT (40.3%) (P = 0.03 and P interim PET/CT (RIW) response was 93.3 ± 4.1 versus 89.6 ± 3.8 (positive vs. negative scan, respectively; P = 0.44). The specificity of posttreatment PET/CT (Deauville) was 95.7% versus 76.4% by CECT (P = 0.006). Posttreatment PET/CT (Deauville) showed significantly inferior overall survival in patients with positive scan versus negative scan results (66.4 ± 22.5 vs. 94.5 ± 2.0, P = 0.029). Conclusion: Interim PET/CT has better specificity, and use of Deauville criteria further improves it. Escalation of therapy based on interim PET in pediatric HL needs further conclusive evidence to justify its use. Posttreatment PET/CT (Deauville) predicts overall survival and has better specificity in comparison to conventional imaging.

  13. Effects of autophagy on multidrug resistance of drug resistant LoVo/Adr cells of colon carcinoma

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    Qiang MA

    2013-11-01

    Full Text Available Objective To observe the effects of autophagy on multidrug resistance (MDR of drug resistant LoVo/Adr cells of colon carcinoma. Methods The formation of autophagosomes was monitored with transmission electron microscopy, and autophagy rate was measured with the aid of MDC staining and flow cytometry. IC50 value of adriamycin (ADR on colon carcinoma cells was detected by MTT assay. The mRNA level of MDR1 gene was measured by RT-PCR, and P-gp protein expression was detected by Western blotting. Results The sporadic autophagosomes or green epoptic dots were found to distribute in LoVo/Adr cells with an autophagy rate of 3.1%±0.5%. A large number of autophagosomes were seen after being treated with ADR or rapamycin (RAPA with the autophagy rates of 33.6%±5.1% and 45.2%±6.1%, respectively (P<0.05. After being treated with ADR combining RAPA, autophagosomes appeared abundantly with an autophagy rate of 76.2%±7.4%, which was significantly higher than that when treated with ADR or RAPA alone (P<0.05. The IC50 value of LoVo/Adr cells on ADR was 3.05±0.52mg/L, which decreased to 1.12±0.21mg/L after being treated with RAPA (P<0.01. RAPA could reverse MDR with a reversal ratio of 2.26. High expression of mRNA and protein of MDR1 gene were observed in LoVo/Adr cells. When treated with RAPA, the expression of MDR1 mRNA decreased from 1.42±0.31 to 0.54±0.20 (P<0.05, and the expression of P-gp protein also decreased significantly from 0.67±0.14 to 0.15±0.08 (P<0.01. Conclusion MDR LoVo/Adr cell shows a low autophagic activity, and RAPA can reverse MDR by increasing autophagy activity. The reversal path might be related with the increase of cell autophagic death and the decrease in MDR1 gene expression in LoVo/Adr cells. DOI: 10.11855/j.issn.0577-7402.2013.11.007

  14. The hypoxia-mimetic agent CoCl₂ induces chemotherapy resistance in LOVO colorectal cancer cells.

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    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

  15. In vitro detection of mdr1 mRNA in murine leukemia cells with {sup 111}In-labeled oligonucleotide

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    Bai Jingming; Yokoyama, Kunihiko; Kinuya, Seigo; Michigishi, Takatoshi; Tonami, Norihisa [Kanazawa University Graduate School of Medical Sciences, Department of Biotracer Medicine (Nuclear Medicine), Kanazawa (Japan); Shiba, Kazuhiro [Kanazawa University, Radioisotope Center, Kanazawa (Japan); Matsushita, Ryo [Kanazawa University, Laboratory for Development of Medicine, Faculty of Pharmaceutical Sciences, Kanazawa (Japan); Nomura, Masaaki [Kanazawa University Hospital, Hospital Pharmacy, Kanazawa (Japan)

    2004-11-01

    The feasibility of intracellular mdr1 mRNA expression detection with radiolabeled antisense oligonucleotide (ODN) was investigated in the murine leukemia cell line, P388/S, and its subclonal, adriamycin-resistant cell line, P388/R. The expression level of mdr1 mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Existence of the multidrug resistance (MDR) phenomenon was assessed via cellular uptake of {sup 99m}Tc-sestamibi (MIBI), a known substrate for P-glycoprotein. A 15-mer phosphorothioate antisense ODN complementary to the sequences located at -1 to 14 of mdr1 mRNA and its corresponding sense ODN were conjugated with the cyclic anhydride of diethylene triamine penta-acetic acid (cDTPA) via an amino group linked to the terminal phosphate at the 5' end at pH 8-9. The DTPA-ODN complexes at concentrations of 0.1-17.4 {mu}Mwere reacted with {sup 111}InCl{sub 3} at pH 5 for 1 h. The hybridization affinity of labeled ODN was evaluated with size-exclusion high-performance liquid chromatography following incubation with the complementary sequence. Cellular uptake of labeled ODN was examined in vitro. Furthermore, enhancing effects of synthetic lipid carriers (Transfast) on transmembrane delivery of ODN were assessed. P388/R cells displayed intense mdr1 mRNA expression in comparison with P388/S cells. {sup 99m}Tc-MIBI uptake in P388/S cells was higher than that in P388/R cells. Specific radioactivity up to 1,634 MBq/nmol was achieved via elevation of added radioactivity relative to ODN molar amount. The hybridization affinity of antisense {sup 111}In-ODN was preserved at approximately 85% irrespective of specific activity. Cellular uptake of antisense {sup 111}In-ODN did not differ from that of sense {sup 111}In-ODN in either P388/S cells or P388/R cells. However, lipid carrier incorporation significantly increased transmembrane delivery of {sup 111}In-ODN; moreover, specific uptake of antisense {sup 111}In-ODN was demonstrated in P388/R

  16. 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

  17. ASSOCIATION BETWEEN RADIOTHERAPY VS NO RADIOTHERAPY BASED ON EARLY RESPONSE TO VAMP CHEMOTHERAPY AND SURVIVAL AMONG CHILDREN WITH FAVORABLE RISK HODGKIN LYMPHOMA

    Science.gov (United States)

    Metzger, Monika L.; Weinstein, Howard J.; Hudson, Melissa M.; Billett, Amy L.; Larsen, Eric C.; Friedmann, Alison; Howard, Scott C.; Donaldson, Sarah S.; Krasin, Matthew J.; Kun, Larry E.; Marcus, Karen J.; Yock, Torunn I.; Tarbell, Nancy; Billups, Catherine A.; Wu, Jianrong; Link, Michael P.

    2012-01-01

    Context Maintaining excellent cure rates in pediatric Hodgkin lymphoma while minimizing toxicity. Objective To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin, methotrexate, and prednisone (VAMP) in patients with favorable risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Design, Setting, and Patients Multi-institutional, unblinded, non-randomized single group phase II clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (< 3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000 through December 9, 2008. Data frozen March 12, 2012. Interventions Patients who achieved a complete response (n=47) after 2 cycles received no radiotherapy, and those with less than complete response (n=41) were given 25.5 Gy involved field radiotherapy. Main Outcome Measures 2-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Results Two-year event-free survival was 90.8% (95% CI, 84.7% – 96.9%); for patients who did not require radiotherapy it was 89.4% (95% CI, 80.8% – 98%), compared with 92.5% (95% CI, 84.5% – 100%) for those who did (P=0.61). Most common acute side effects were neuropathic pain (2% of patients), nausea/vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or non-neutropenic infection. Long term side effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each, subclinical pulmonary dysfunction in 12 patients (26%) and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were

  18. The 2013 Discovery Award from the Society for Free Radical Biology and Medicine: Selected Discoveries from the Butterfield Laboratory of Oxidative Stress and Its Sequelae in Brain in Cognitive Disorders Exemplified by Alzheimer Disease and Chemotherapy Induced Cognitive Impairment

    Science.gov (United States)

    Butterfield, D. Allan

    2014-01-01

    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 pro-inflammatory 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

  19. Overcoming of multidrug resistance by introducing the apoptosis gene, bcl-Xs, into MRP-overexpressing drug resistant cells.

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    Ohi, Y; Kim, R; Toge, T

    2000-05-01

    Multidrug resistance associated protein (MRP) is one of drug transport membranes that confer multidrug resistance in cancer cells. Multidrug resistance has been known to be associated with resistance to apoptosis. In this study, using MRP overexpressing multidrug resistant nasopharyngeal cancer cells, we examined the expression of apoptosis related genes including p53, p21WAF1, bax and bcl-Xs between drug sensitive KB and its resistant KB/7D cells. We also exam