AIM:To determine the influence of Adriamycin(ADM)on the changes in Nanog,Oct4,Sox2,as well as,in ARID1 and Wnt5b expression in liver cancer stem cells.METHODS:The MHCC97-L and HCCLM3 liver cancer cell lines were selec...AIM:To determine the influence of Adriamycin(ADM)on the changes in Nanog,Oct4,Sox2,as well as,in ARID1 and Wnt5b expression in liver cancer stem cells.METHODS:The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study,and were routinely cultured.The 50%lethal dose(LD50)in the cell lines was detected by the MTT assay.Expression changes in liver cancer stem cell related genes(Nanog,Oct-4,Sox2,ARID1,and Wnt5b)were detected by western blot following treatment with ADM(LD50).RESULTS:The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells(0.4123±0.0236μmol/L vs 0.5259±0.0125μmol/L,P<0.05).Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells,while only Sox2 was expressed in HCCLM3cells.However,neither ARID1A nor Oct4 was detected in these two cell lines.Genes,related to the stem cells,showed different expression in liver cancer cells with different metastatic potential following treatment with ADM(LD50).Wnt5b protein increased gradually within4 h of ADM(LD50)treatment,while Nanog decreased(P<0.05).After 12 h,Wnt5b decreased gradually,while Nanog increased steadily(P<0.05).In addition,only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM(LD50)treatment.The expression of Sox2 increased gradually with ADM(LD50)in HCCLM3 cells(P<0.05).CONCLUSION:ADM increased the death rate of MHCC97-L and HCCLM3 cells,while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.展开更多
AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these chan...AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes.METHODS: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDGPET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the preand posttherapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium.RESULTS: We observed a significant change in SUVmean values in the myocardium (defined as more than change in cardiac SUVmean between pre-and post-chemotherapy PET) in 1 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both preand post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the followup 18 F-FDG-PET study. Group A (n = 8): showed an increase in cardiac 18 F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac 18 F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac 18 F-FDG uptake in the posttherapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m 2 ) received during the time of the follow-up FDG-PET study was 256. 25, 250 and 137.5, respectively.CONCLUSION: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.展开更多
The adriamycin magnetic microspheres (ADM-MAMs) were prepared by the heat-stabilized protein methods. Their physico-chemical properties were examined; their cytotoxicities against tumor cells in vitro were assayed by ...The adriamycin magnetic microspheres (ADM-MAMs) were prepared by the heat-stabilized protein methods. Their physico-chemical properties were examined; their cytotoxicities against tumor cells in vitro were assayed by a modi-fied MTT method, and their effects were observed on the implanted gastric tumor in Wistar rats given ADM-MAMs via alimentary canal at the presence of the ex-ternal magnetic fields. The results showed that the ADM-MAMs were successful-ly prepared and had cytotoxic effect on tumor cells in vitro similar to the free ADM (P>0. 05). The inhibitory effects of ADM-MAMs on the implanted gastric tumor in vivo were significantly increased as compared with the controls (P<0.01). Our results suggested that ADM-MAMs were a new type of adriamycin (ADM) preparation and its form alteration did not affect its anticancer effects.展开更多
Matrix metalloproteinase-2 (MMP-2) level and the ERK1/2 signal pathway are dependent factors for the growth and metastasis of cancer.However,the impact of MMP-2 in combination with ERK1/2 in tumor patients with drug r...Matrix metalloproteinase-2 (MMP-2) level and the ERK1/2 signal pathway are dependent factors for the growth and metastasis of cancer.However,the impact of MMP-2 in combination with ERK1/2 in tumor patients with drug resistance is unknown.To determine the relationship between MMP-2 and the ERK1/2 signal pathway,we established an adriamycin (ADM)-induced MG-63 (ADM-MG-63) cell line.With the increase of the ERK1/2 pathway blocker PD98059,we detected the expression levels of MMP-2 and p-ERK1/2 by Western blot in ADM-MG-63 cells.In ADM-MG-63 cells transfected with MMP-2-siRNA,the expression of ERK1/2 was detected for understanding the function of the ERK1/2 signal pathway.Three siRNAs for MMP-2 (MMP-2-siRNA) were designed,and the optimal one was selected and tested at different time points of 24,48 and 72 h.Under an ADM-induced condition,ADM-MG-63 cells were finally stable living in the medium of ADM (200 ng/mL).PD98059 could effectively suppress the expression levels of p-ERK1/2 and MMP-2.When the MMP-2 was silenced by using MMP-2-siRNA,the expression of p-ERK1/2 was enhanced.It is con-cluded that MMP-2 may be involved in ADM resistance dependent on ERK1/2 signal pathway,sug-gesting interference in ERK1/2 may be a new method of targeted therapy for tumor resistance.展开更多
To study the relationship between serum vascular endothelial growth factor (VEGF) and proteinuria in adriamycin induced nephrotic rats, a rat model of adriamycin induced nephrotitis was developed by injection of adria...To study the relationship between serum vascular endothelial growth factor (VEGF) and proteinuria in adriamycin induced nephrotic rats, a rat model of adriamycin induced nephrotitis was developed by injection of adriamycin into a tail vein in a rat. At different time points, 24 h urinary protein excretion was measured by using Coomassie brilliant blue method and the serum VEGF levels detected by using ELISA assay. The interventional effect of VEGF on this model was observed. The results showed that: (1) The adriamycin induced nephrotic syndrome rat model was developed successfully; (2) Serum VEGF levels and proteinuria were significantly increased at 7th day after intravenous injection of adriamycin. There was a positive correlation between serum VEGF levels and 24 h urinary protein excretion ( r=0.67, P <0.05). (3) The 24 h urinary protein excretion was significantly increased in the rats receiving administration of VEGF ( P <0.05). It was concluded that VEGF might play an important role in the pathogenesis of proteinuria in adriamycin induced nephrotic rats.展开更多
The targeting of antineoplastic agents to restricted anatomic sites and specific target cells have been challenged clinicians all the time in cancer chemotherapy, which resulted in recent efforts to focus the effects ...The targeting of antineoplastic agents to restricted anatomic sites and specific target cells have been challenged clinicians all the time in cancer chemotherapy, which resulted in recent efforts to focus the effects of existing antitumor agents and treatments on tumor cells and spare their effects on normal cells. The drug-carrier complex, adriamycin carried by magnetic albumin microspheres (ADM-MAM) was prepared by using our discovered new and modified method. The physical feature of the prepared drug-carrier microspheres was much better than by the traditional method in comparison. The successful preparation of the drug-carrier complex, ADM-MAM, is one of the key steps for our later further researches in the targeted chemotherapy.展开更多
AIM:To investigate the influence of mycophenolate mofetil(MMF)plus adriamycin(ADM)on hepatocellular carcinoma(HCC)cells. METHODS:HCC cells were treated with 100μg/ml of MMF alone(MMF group),1μg/mL of adriamycin(ADM ...AIM:To investigate the influence of mycophenolate mofetil(MMF)plus adriamycin(ADM)on hepatocellular carcinoma(HCC)cells. METHODS:HCC cells were treated with 100μg/ml of MMF alone(MMF group),1μg/mL of adriamycin(ADM group)alone,or a combination of the drugs(MMF+ ADM group).We performed an 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide(MTT)assay to measure the growth inhibition rate of HCC cells.Flow cytometry was used to determine the percentage of cells in different phases of the cell cycle and the number of apoptotic cells.Hoechst 33258 staining revealed the morphological changes associated with apoptosis in HCC cells. RESULTS:The results of MTT assays revealed that monotherapy with ADM or MMF showed inhibition of cell growth,while MMF+ADM therapy afforded an inhibition rate of more than 90%with cell distribution in G1 and G2/M phase greater than that in S phase. MMF+ADM treatment also downregulated Bcl-2 expression markedly.The growth of HCC cells was markedly inhibited and apoptosis was enhanced in all the 3 groups.Compared with other 2 groups,the MMF +ADM group showed more obvious apoptosis of cells. CONCLUSION:The MMF plus ADM combination exerts remarkable inhibitory effects on the growth of HCC cells.展开更多
Objective: To explore the protective effects of ursolic acid (UA) on adriamycin nephropathy in mice. Methods: Totally 40 male Balb/c mice were randomly divided into normal group, model group, low dose of UA group and ...Objective: To explore the protective effects of ursolic acid (UA) on adriamycin nephropathy in mice. Methods: Totally 40 male Balb/c mice were randomly divided into normal group, model group, low dose of UA group and high dose of UA group. One-time injection of Adriamycin (ADR) at 10.0 mg/kg via tail vein was used to establish the model. Different doses of UA were administered to the mice in treatment groups from the first day after successful modeling. After 3 consecutive weeks, 24 h urine protein was measured, and BUN, Scr and TG as well as SOD, MDA and GSH were also measured. The IL-1β, TNF-α and TGF-β1 were measured by ELISA;SMAD2/3 phosphorylation and its target protein α-SMA expression were measured by Western Blot;pathological changes of renal tissues were observed. Results: Compared with the model group, UA can significantly reduce the urine protein, BUN, Scr, TG, MDA, IL-1β, TNF-α, TGF-β and SMAD2/3 phosphorylation and its target protein α-SMA expression while increasing the GSH and SOD, and the difference is significant (P Conclusions: Ursolic acid can protect against renal damage by inhibiting oxidative stress and reducing the release of inflammatory cytokines, which may be related to the inhibition of TGF-β1/Smads-related signaling pathway.展开更多
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: Th...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.展开更多
Apoptosis of tumor cells have become a newstandard for chemotherapy. It is useful to demonstrateinduction of apoptosis in tumor cells by anti-cancer drugsin vivo. We reported the results of apoptosis induction inmurin...Apoptosis of tumor cells have become a newstandard for chemotherapy. It is useful to demonstrateinduction of apoptosis in tumor cells by anti-cancer drugsin vivo. We reported the results of apoptosis induction inmurine tumor cell line S-180 and it’s resistant cell linc S-180R by adriamycin in different dose and different time.We found that apoptosis in S-180 cells could be inducedby low dose of adriamycin, the apoptosis was started at 24h. after the administration, and reached to 62.5% of thecells to apptosis until 72 h. Comparison with theparental cell line, only 13% of S-180R cells wereapoptosed. At high dose, 20% of S-180R cells wereapoptosed, whereas, almost all S-180 cells were killed inthe same time. The lymphocytes were appeared inabdominal cavity of the mice after treatment ofadriamycin for 24 h. It was very interested to find outthat there was no lymphocyte left in the abdominal cavityof the mice with S-180R cells treated at high dose ofadriamycin.展开更多
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...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 X 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.展开更多
Objective: To studied the effect of Diethyldithio-carbamate (DDC) on the antitumor activity of adriamycin (ADM) nanoparticle-lipiodol emulsion. Methods: The SD rats bearing liver carcinoma were divided into six groups...Objective: To studied the effect of Diethyldithio-carbamate (DDC) on the antitumor activity of adriamycin (ADM) nanoparticle-lipiodol emulsion. Methods: The SD rats bearing liver carcinoma were divided into six groups and treated by saline, adriamycin, adriamycin nanoparticle-lipiodol emulsion, adriamycin liposome-lipiodol emulsion,DDC plus adriamycin nanoparticle-lipiodol emulsion, DDC plus adriamycin liposome-lipiodol emulsion respectively.The volume of the tumors, tumor growth rate (G%) and life prolonging rate PL% in six groups were determined.Results: The values of the IC50 (mg/ml) of adriamycin were reduced from 18.40 to 0.74 for the resistant cellsSGC7901/CVR, and from 4.00 to 0.32 for the sensitive cells SGC7901/WT by pretreating the tumor cells with DDC. The tumor growth rate (G%) and life prolonging rate PL% increased significantly (P<0.05) in the DDC pretreatedgroups than adriamycin nanoparticle-lipiodol or adriamycin liposome-lipiodol emulsion groups. Conclusion: Theantitumor effect of adriamycin can be enhanced byinhibiting the superoxide dismutase (SOD) in tumor cells by DDC.展开更多
Diabetic cardiomyopathy is one of the life threatening complications of diabetes. A number of animal models are being used for studying diabetic cardiomyopathy. In laboratory animal models, induction of cardiomyopathy...Diabetic cardiomyopathy is one of the life threatening complications of diabetes. A number of animal models are being used for studying diabetic cardiomyopathy. In laboratory animal models, induction of cardiomyopathy happens in two stages: first being the induction of diabetic condition and the second being the induction of cardiomyopathy by prolonging diabetic condition. It takes a longer time to develop diabetes with the limited success rate for development of cardiomyopathy. Adriamycin is an effective anticancer drug limited by its major side-effect cardiomyopathy. A number of features of Adriamycin treatment mimics diabetes. We postulate that Adriamycin-induced cardiomyopathy might be used as a model system to study diabetic cardiomyopathy in rodents since a number of features of both the cardiomyopathies overlap. Left ventricular hypertrophy, systolic and diastolic dysfunction, myofibrillar loss, and fibrosis are hallmarks of both of the cardiomyopathies. At the molecular level, calcium signaling, endoplasmic reticulum stress, advance glycation endproduct activation, mitochondrial dysfunction,inflammation, lipotoxicity and oxidative stress are similar in both the cardiomyopathies.The signature profile of both the cardiomyopathies shares commonalities. In conclusion,we suggest that Adriamycin induced cardiomyopathic animal model can be used for studying diabetic cardiomyopathy and would save time for researchers working on cardiomyopathy developed in rodent using the traditional method.展开更多
Magnetic albumin microspheres bearing adriamycin (ADM MAM) is a novel chemotherapeutic compound with site specific drug delivery characteristics. The acute and subacute toxic tests of the compound, local irritating te...Magnetic albumin microspheres bearing adriamycin (ADM MAM) is a novel chemotherapeutic compound with site specific drug delivery characteristics. The acute and subacute toxic tests of the compound, local irritating test and anaphylactic test were performed on mice and guinea pigs. The results showed there was no macroscopically and microscopically direct cytotoxic injuries of the compound to the animal organs or to the cells. The LD 50 value of the compound was higher than that of the single used adriamycin, indicating that the compound was less toxic than the single adriamycin and quite safe in its therapeutic dosage. Furthermore, there was also no side effects or toxic reactions to be observed on clinical patients with advanced carcinoma or gastric cancer.展开更多
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 ki...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..展开更多
Objective:To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats.Methods:The rats were divided into 4 groups.The control group received solvent;the p-coumaric acid group was treate...Objective:To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats.Methods:The rats were divided into 4 groups.The control group received solvent;the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days;the adriamycin group was administered with a single dose of adriamycin(15 mg/kg,i.p.),and the p-coumaric acid+adriamycin group was given p-coumaric acid five days before adriamycin administration.Twenty-four hours after the last administration,blood samples were collected for biochemical analysis,and liver tissues were removed for histopathological and immunohistochemistrical studies.Moreover,the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase,superoxide dismutase,and catalase in liver tissue were measured.Results:Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase,alanine transaminase,aspartate transaminase,total bilirubin,total cholesterol,triglyceride,and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin.p-Coumaric acid also raised the levels of glutathione peroxidase,superoxide dismutase,and catalase,as well as decreased lipid peroxidation in liver tissue and hepatic IL-1βexpression.Additionally,histopathological study confirmed the protective effect of p-coumaric acid against liver damage.Conclusions:p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.展开更多
Objective: To observe the inhibitory effect of calcitonin gene--related peptide (CGRP) on adriamycininduced acute cardiotoxicity. Methods: Primarily cultured rat myocardial cells were treated with 10-6 mol/Ladriamycin...Objective: To observe the inhibitory effect of calcitonin gene--related peptide (CGRP) on adriamycininduced acute cardiotoxicity. Methods: Primarily cultured rat myocardial cells were treated with 10-6 mol/Ladriamycin and 10-6mol/L adriamycin + 10 8mol/I. CGRP. Lactate dehydrogenase (LDH ) activity in the mediumand the contents of malondialdehyde (MDA ). calcium. and magnesium in the myocardial cells were assayed.Results: In the adriamycin group, LDH activity in medium and calcium, MDA contents in myocardial cells weresignificantly increased compared with those in control group, and magnesium content in the myocardial cells wassignificantly reduced. In the adriamycin group. there was a positive correlation between LDH activity in themedium and MDA content in the myocardial cells. Meanwhile, in the adriamycin + CGRP group,- CGRP mightsignificantly reduce the leakage of LDH from myocardial cells, lessen the increase in calcium and MDA contentsand prevent the loss of magnesium. Conclusion: CGRP may inhibit adriamycin induced acute cardiotoxicity byinhibiting lipid peroxidation, attenuating calcium overload, magnesium loss, and protecting enzyme activity.展开更多
Nude mouse hepatocytes were transformed by adriamycin(ADM).From mid-passaged transformed cells characterizedby peripheral outgrowths of fibroblasts,epithelial andfibroblastic clones were isolated.Clonal isolates ofthe...Nude mouse hepatocytes were transformed by adriamycin(ADM).From mid-passaged transformed cells characterizedby peripheral outgrowths of fibroblasts,epithelial andfibroblastic clones were isolated.Clonal isolates ofthe fibroblasts retained their fibroblastic phenotypewhereas the epithelioids remained phenotypically unsta-ble from passage to passage.Proliferation展开更多
基金Supported by National Natural Science Foundation,No.81372317
文摘AIM:To determine the influence of Adriamycin(ADM)on the changes in Nanog,Oct4,Sox2,as well as,in ARID1 and Wnt5b expression in liver cancer stem cells.METHODS:The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study,and were routinely cultured.The 50%lethal dose(LD50)in the cell lines was detected by the MTT assay.Expression changes in liver cancer stem cell related genes(Nanog,Oct-4,Sox2,ARID1,and Wnt5b)were detected by western blot following treatment with ADM(LD50).RESULTS:The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells(0.4123±0.0236μmol/L vs 0.5259±0.0125μmol/L,P<0.05).Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells,while only Sox2 was expressed in HCCLM3cells.However,neither ARID1A nor Oct4 was detected in these two cell lines.Genes,related to the stem cells,showed different expression in liver cancer cells with different metastatic potential following treatment with ADM(LD50).Wnt5b protein increased gradually within4 h of ADM(LD50)treatment,while Nanog decreased(P<0.05).After 12 h,Wnt5b decreased gradually,while Nanog increased steadily(P<0.05).In addition,only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM(LD50)treatment.The expression of Sox2 increased gradually with ADM(LD50)in HCCLM3 cells(P<0.05).CONCLUSION:ADM increased the death rate of MHCC97-L and HCCLM3 cells,while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.
文摘AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes.METHODS: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDGPET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the preand posttherapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium.RESULTS: We observed a significant change in SUVmean values in the myocardium (defined as more than change in cardiac SUVmean between pre-and post-chemotherapy PET) in 1 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both preand post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the followup 18 F-FDG-PET study. Group A (n = 8): showed an increase in cardiac 18 F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac 18 F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac 18 F-FDG uptake in the posttherapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m 2 ) received during the time of the follow-up FDG-PET study was 256. 25, 250 and 137.5, respectively.CONCLUSION: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.
文摘The adriamycin magnetic microspheres (ADM-MAMs) were prepared by the heat-stabilized protein methods. Their physico-chemical properties were examined; their cytotoxicities against tumor cells in vitro were assayed by a modi-fied MTT method, and their effects were observed on the implanted gastric tumor in Wistar rats given ADM-MAMs via alimentary canal at the presence of the ex-ternal magnetic fields. The results showed that the ADM-MAMs were successful-ly prepared and had cytotoxic effect on tumor cells in vitro similar to the free ADM (P>0. 05). The inhibitory effects of ADM-MAMs on the implanted gastric tumor in vivo were significantly increased as compared with the controls (P<0.01). Our results suggested that ADM-MAMs were a new type of adriamycin (ADM) preparation and its form alteration did not affect its anticancer effects.
基金supported by a grant from the Major State Basic Research Development of China (No. 2002CB513107)
文摘Matrix metalloproteinase-2 (MMP-2) level and the ERK1/2 signal pathway are dependent factors for the growth and metastasis of cancer.However,the impact of MMP-2 in combination with ERK1/2 in tumor patients with drug resistance is unknown.To determine the relationship between MMP-2 and the ERK1/2 signal pathway,we established an adriamycin (ADM)-induced MG-63 (ADM-MG-63) cell line.With the increase of the ERK1/2 pathway blocker PD98059,we detected the expression levels of MMP-2 and p-ERK1/2 by Western blot in ADM-MG-63 cells.In ADM-MG-63 cells transfected with MMP-2-siRNA,the expression of ERK1/2 was detected for understanding the function of the ERK1/2 signal pathway.Three siRNAs for MMP-2 (MMP-2-siRNA) were designed,and the optimal one was selected and tested at different time points of 24,48 and 72 h.Under an ADM-induced condition,ADM-MG-63 cells were finally stable living in the medium of ADM (200 ng/mL).PD98059 could effectively suppress the expression levels of p-ERK1/2 and MMP-2.When the MMP-2 was silenced by using MMP-2-siRNA,the expression of p-ERK1/2 was enhanced.It is con-cluded that MMP-2 may be involved in ADM resistance dependent on ERK1/2 signal pathway,sug-gesting interference in ERK1/2 may be a new method of targeted therapy for tumor resistance.
文摘To study the relationship between serum vascular endothelial growth factor (VEGF) and proteinuria in adriamycin induced nephrotic rats, a rat model of adriamycin induced nephrotitis was developed by injection of adriamycin into a tail vein in a rat. At different time points, 24 h urinary protein excretion was measured by using Coomassie brilliant blue method and the serum VEGF levels detected by using ELISA assay. The interventional effect of VEGF on this model was observed. The results showed that: (1) The adriamycin induced nephrotic syndrome rat model was developed successfully; (2) Serum VEGF levels and proteinuria were significantly increased at 7th day after intravenous injection of adriamycin. There was a positive correlation between serum VEGF levels and 24 h urinary protein excretion ( r=0.67, P <0.05). (3) The 24 h urinary protein excretion was significantly increased in the rats receiving administration of VEGF ( P <0.05). It was concluded that VEGF might play an important role in the pathogenesis of proteinuria in adriamycin induced nephrotic rats.
基金This project was supported by a grant from the NationalHealth Ministry(No.6 716 8)
文摘The targeting of antineoplastic agents to restricted anatomic sites and specific target cells have been challenged clinicians all the time in cancer chemotherapy, which resulted in recent efforts to focus the effects of existing antitumor agents and treatments on tumor cells and spare their effects on normal cells. The drug-carrier complex, adriamycin carried by magnetic albumin microspheres (ADM-MAM) was prepared by using our discovered new and modified method. The physical feature of the prepared drug-carrier microspheres was much better than by the traditional method in comparison. The successful preparation of the drug-carrier complex, ADM-MAM, is one of the key steps for our later further researches in the targeted chemotherapy.
基金Supported by the Science and Technique Foundation of Shaanxi Province,No.2005K09-G12
文摘AIM:To investigate the influence of mycophenolate mofetil(MMF)plus adriamycin(ADM)on hepatocellular carcinoma(HCC)cells. METHODS:HCC cells were treated with 100μg/ml of MMF alone(MMF group),1μg/mL of adriamycin(ADM group)alone,or a combination of the drugs(MMF+ ADM group).We performed an 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide(MTT)assay to measure the growth inhibition rate of HCC cells.Flow cytometry was used to determine the percentage of cells in different phases of the cell cycle and the number of apoptotic cells.Hoechst 33258 staining revealed the morphological changes associated with apoptosis in HCC cells. RESULTS:The results of MTT assays revealed that monotherapy with ADM or MMF showed inhibition of cell growth,while MMF+ADM therapy afforded an inhibition rate of more than 90%with cell distribution in G1 and G2/M phase greater than that in S phase. MMF+ADM treatment also downregulated Bcl-2 expression markedly.The growth of HCC cells was markedly inhibited and apoptosis was enhanced in all the 3 groups.Compared with other 2 groups,the MMF +ADM group showed more obvious apoptosis of cells. CONCLUSION:The MMF plus ADM combination exerts remarkable inhibitory effects on the growth of HCC cells.
文摘Objective: To explore the protective effects of ursolic acid (UA) on adriamycin nephropathy in mice. Methods: Totally 40 male Balb/c mice were randomly divided into normal group, model group, low dose of UA group and high dose of UA group. One-time injection of Adriamycin (ADR) at 10.0 mg/kg via tail vein was used to establish the model. Different doses of UA were administered to the mice in treatment groups from the first day after successful modeling. After 3 consecutive weeks, 24 h urine protein was measured, and BUN, Scr and TG as well as SOD, MDA and GSH were also measured. The IL-1β, TNF-α and TGF-β1 were measured by ELISA;SMAD2/3 phosphorylation and its target protein α-SMA expression were measured by Western Blot;pathological changes of renal tissues were observed. Results: Compared with the model group, UA can significantly reduce the urine protein, BUN, Scr, TG, MDA, IL-1β, TNF-α, TGF-β and SMAD2/3 phosphorylation and its target protein α-SMA expression while increasing the GSH and SOD, and the difference is significant (P Conclusions: Ursolic acid can protect against renal damage by inhibiting oxidative stress and reducing the release of inflammatory cytokines, which may be related to the inhibition of TGF-β1/Smads-related signaling pathway.
文摘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.
文摘Apoptosis of tumor cells have become a newstandard for chemotherapy. It is useful to demonstrateinduction of apoptosis in tumor cells by anti-cancer drugsin vivo. We reported the results of apoptosis induction inmurine tumor cell line S-180 and it’s resistant cell linc S-180R by adriamycin in different dose and different time.We found that apoptosis in S-180 cells could be inducedby low dose of adriamycin, the apoptosis was started at 24h. after the administration, and reached to 62.5% of thecells to apptosis until 72 h. Comparison with theparental cell line, only 13% of S-180R cells wereapoptosed. At high dose, 20% of S-180R cells wereapoptosed, whereas, almost all S-180 cells were killed inthe same time. The lymphocytes were appeared inabdominal cavity of the mice after treatment ofadriamycin for 24 h. It was very interested to find outthat there was no lymphocyte left in the abdominal cavityof the mice with S-180R cells treated at high dose ofadriamycin.
文摘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 X 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.
基金This work was supported by the National Natural Science Foundation of China (No. 39390191 No. 30170271)
文摘Objective: To studied the effect of Diethyldithio-carbamate (DDC) on the antitumor activity of adriamycin (ADM) nanoparticle-lipiodol emulsion. Methods: The SD rats bearing liver carcinoma were divided into six groups and treated by saline, adriamycin, adriamycin nanoparticle-lipiodol emulsion, adriamycin liposome-lipiodol emulsion,DDC plus adriamycin nanoparticle-lipiodol emulsion, DDC plus adriamycin liposome-lipiodol emulsion respectively.The volume of the tumors, tumor growth rate (G%) and life prolonging rate PL% in six groups were determined.Results: The values of the IC50 (mg/ml) of adriamycin were reduced from 18.40 to 0.74 for the resistant cellsSGC7901/CVR, and from 4.00 to 0.32 for the sensitive cells SGC7901/WT by pretreating the tumor cells with DDC. The tumor growth rate (G%) and life prolonging rate PL% increased significantly (P<0.05) in the DDC pretreatedgroups than adriamycin nanoparticle-lipiodol or adriamycin liposome-lipiodol emulsion groups. Conclusion: Theantitumor effect of adriamycin can be enhanced byinhibiting the superoxide dismutase (SOD) in tumor cells by DDC.
基金financially supported by the Department of Science and Technology and Science and Engineering Research Board,New Delhi through the provided grant-in aid(Grant number:SB/YS/LS-99/2013)
文摘Diabetic cardiomyopathy is one of the life threatening complications of diabetes. A number of animal models are being used for studying diabetic cardiomyopathy. In laboratory animal models, induction of cardiomyopathy happens in two stages: first being the induction of diabetic condition and the second being the induction of cardiomyopathy by prolonging diabetic condition. It takes a longer time to develop diabetes with the limited success rate for development of cardiomyopathy. Adriamycin is an effective anticancer drug limited by its major side-effect cardiomyopathy. A number of features of Adriamycin treatment mimics diabetes. We postulate that Adriamycin-induced cardiomyopathy might be used as a model system to study diabetic cardiomyopathy in rodents since a number of features of both the cardiomyopathies overlap. Left ventricular hypertrophy, systolic and diastolic dysfunction, myofibrillar loss, and fibrosis are hallmarks of both of the cardiomyopathies. At the molecular level, calcium signaling, endoplasmic reticulum stress, advance glycation endproduct activation, mitochondrial dysfunction,inflammation, lipotoxicity and oxidative stress are similar in both the cardiomyopathies.The signature profile of both the cardiomyopathies shares commonalities. In conclusion,we suggest that Adriamycin induced cardiomyopathic animal model can be used for studying diabetic cardiomyopathy and would save time for researchers working on cardiomyopathy developed in rodent using the traditional method.
基金This project was supported by a grant from the National Key Tasks'foundation(No.96 90 6 0 116 )
文摘Magnetic albumin microspheres bearing adriamycin (ADM MAM) is a novel chemotherapeutic compound with site specific drug delivery characteristics. The acute and subacute toxic tests of the compound, local irritating test and anaphylactic test were performed on mice and guinea pigs. The results showed there was no macroscopically and microscopically direct cytotoxic injuries of the compound to the animal organs or to the cells. The LD 50 value of the compound was higher than that of the single used adriamycin, indicating that the compound was less toxic than the single adriamycin and quite safe in its therapeutic dosage. Furthermore, there was also no side effects or toxic reactions to be observed on clinical patients with advanced carcinoma or gastric cancer.
文摘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..
基金supported by a grant from the Deputy of Research and Technology Development of Ahvaz Jundishapur University of Medical Sciences(Grant No.97s55)
文摘Objective:To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats.Methods:The rats were divided into 4 groups.The control group received solvent;the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days;the adriamycin group was administered with a single dose of adriamycin(15 mg/kg,i.p.),and the p-coumaric acid+adriamycin group was given p-coumaric acid five days before adriamycin administration.Twenty-four hours after the last administration,blood samples were collected for biochemical analysis,and liver tissues were removed for histopathological and immunohistochemistrical studies.Moreover,the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase,superoxide dismutase,and catalase in liver tissue were measured.Results:Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase,alanine transaminase,aspartate transaminase,total bilirubin,total cholesterol,triglyceride,and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin.p-Coumaric acid also raised the levels of glutathione peroxidase,superoxide dismutase,and catalase,as well as decreased lipid peroxidation in liver tissue and hepatic IL-1βexpression.Additionally,histopathological study confirmed the protective effect of p-coumaric acid against liver damage.Conclusions:p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.
文摘Objective: To observe the inhibitory effect of calcitonin gene--related peptide (CGRP) on adriamycininduced acute cardiotoxicity. Methods: Primarily cultured rat myocardial cells were treated with 10-6 mol/Ladriamycin and 10-6mol/L adriamycin + 10 8mol/I. CGRP. Lactate dehydrogenase (LDH ) activity in the mediumand the contents of malondialdehyde (MDA ). calcium. and magnesium in the myocardial cells were assayed.Results: In the adriamycin group, LDH activity in medium and calcium, MDA contents in myocardial cells weresignificantly increased compared with those in control group, and magnesium content in the myocardial cells wassignificantly reduced. In the adriamycin group. there was a positive correlation between LDH activity in themedium and MDA content in the myocardial cells. Meanwhile, in the adriamycin + CGRP group,- CGRP mightsignificantly reduce the leakage of LDH from myocardial cells, lessen the increase in calcium and MDA contentsand prevent the loss of magnesium. Conclusion: CGRP may inhibit adriamycin induced acute cardiotoxicity byinhibiting lipid peroxidation, attenuating calcium overload, magnesium loss, and protecting enzyme activity.
文摘Nude mouse hepatocytes were transformed by adriamycin(ADM).From mid-passaged transformed cells characterizedby peripheral outgrowths of fibroblasts,epithelial andfibroblastic clones were isolated.Clonal isolates ofthe fibroblasts retained their fibroblastic phenotypewhereas the epithelioids remained phenotypically unsta-ble from passage to passage.Proliferation
