AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation ...AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> Since there has been training, there has been discussion about the effect o...<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> Since there has been training, there has been discussion about the effect of training. But training evaluation is not systematic until Kirkpatrick came up with the training evaluation model in 1959. At present, the prevailing model in the systematic summary of training evaluation is still The Kirkpatrick’s model. This model was further improved in 1994, more responsive to contemporary needs, and thus widely used all over the world. At the beginning, it was widely used in human resource management of enterprises. In recent years, this model has been gradually used in the medical field to evaluate the effect of medical training. The Kirkpatrick’s model has a systematic, integrated and persuasive evaluation system for trainees. It has good effects in the pre-service nurse training, the professional image and code of conduct nurses training, and the geriatric nurse training. At present, there are few studies on the chemotherapeutic drug training of neurologist nurses in China. In clinical work, nurses’ cognitive and practical behaviors of chemotherapeutic drug protection and drug extravasation prevention and treatment are insufficient. It directly harms the health of nursing staff and increases the complications of chemotherapy, increases pain of tumor patients, delays or interrupts chemotherapy, and aggravates the economic burden of patients. Especially, Chemotherapeutic drugs for neuro-oncology have particularity and necessity of urgent training. <strong>Objective:</strong> To investigate the effect of chemotherapeutic drug training through mobile terminal for neuro-oncology nurses based on the Kirkpatrick’s model. <strong>Methods: </strong>The training content and evaluation questionnaire for chemotherapeutic drugs were designed by nursing management personnel and senior nurses in our department according to the guidelines and common diseases requiring chemotherapy in the department. The content includes the basic knowledge of neuro-oncology chemotherapy, pharmacological knowledge, toxic and side effect of chemotherapy, etc., which are regularly pushed through the mobile terminal-WeChat. Forty nurses participated in the training and the effect is evaluated by Kirkpatrick’s model. <strong>Result:</strong> After the training, 100% of nurses were satisfied with the training content and 97.5% with the training form. The scores of nurses in learning level such as basic pharmacological knowledge, drug configuration and exposure, drug treatment and infusion, observation of toxic and side effects, and treatment of drug extravasation were significantly higher than those before the training (P < 0.01). The scores of nurses in the behavior level such as drug allocation, health education, toxic and side effect observation and prediction, treatment of exosmosis, occupational protection were significantly higher than those before the training. After the training, the satisfaction of managers, chemotherapy physicians and chemotherapy patients on the behavior of nurses was significantly higher than that before the training (P < 0.01). <strong>Conclusion:</strong> The chemotherapeutic drug training through mobile terminal based on Kirkpatrick’s model can improve the ability of neuro-oncology nurses, so as to improve the satisfaction of physicians and patients.</span> </div>展开更多
The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can sele...The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m RNAs.Therefore,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy.Due to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the co-delivery.In this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.展开更多
AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemothera...AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.展开更多
目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D...目的构建并表征胃癌三维多细胞球体模型,用于评价化疗药物的瘤内穿透。方法将12000个小鼠胃癌MFC细胞系接种于96 U 3D细胞培养板,以构建MFC多细胞肿瘤球体(MFC MCTS);将8000个MFC细胞和4000个小鼠成纤维NIH/3T3细胞系共同接种于96 U 3D细胞培养板,以构建MFC-NIH/3T3共培养多细胞肿瘤球体(CO MCTS);通过活细胞成像表征球体的直径、圆度、面积和透光率;通过激光共聚焦成像表征球体微环境和化疗药物(LipoDOX,5.0μg/ml)的瘤内穿透。结果培养5 d时,两种球体的透光率最低,圆度>0.90,直径约为530μm,面积约为0.23 mm^(2)。两种球体模型内均检测到3种微环境荧光探针分布。LipoDOX能相对均匀地穿透MFC MCTS,却在CO MCTS内表现出外多内少的不均匀穿透,药物荧光强度降低约58.3%(P<0.01)。结论本研究构建了两种具有良好圆度、高紧实度、适中直径和面积的胃癌三维多细胞球体模型,两种胃癌球体模型均表现出酸性、缺氧和氧化还原微环境,可精准、高效地评价化疗药物的瘤内穿透。展开更多
Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization.Many strategies have been evaluated to reduce the incidence of PES,...Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization.Many strategies have been evaluated to reduce the incidence of PES,but no standard prevention guidelines currently exist.In a single-center,placebo-controlled trial,Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES(from 80%to 6%),of post-procedural liver decompensation(from 14%to 0%),and a shorter hospital stay(4 days vs 6 days),alongside an acceptable safety profile.The results of this study raise several controversial points regarding their applicability in the Western world.In the West,there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis,so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis.Furthermore,in the West,there is a preferred use of drug-eluting beads loaded with doxorubicin,which are associated with a lower incidence of PES.A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.展开更多
基金Supported by the National Nature Science Foundation of China, No. 39870879Key Technologies R and D Program of China, No. 2002AA2Z3337
文摘AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong>Background:</strong> Since there has been training, there has been discussion about the effect of training. But training evaluation is not systematic until Kirkpatrick came up with the training evaluation model in 1959. At present, the prevailing model in the systematic summary of training evaluation is still The Kirkpatrick’s model. This model was further improved in 1994, more responsive to contemporary needs, and thus widely used all over the world. At the beginning, it was widely used in human resource management of enterprises. In recent years, this model has been gradually used in the medical field to evaluate the effect of medical training. The Kirkpatrick’s model has a systematic, integrated and persuasive evaluation system for trainees. It has good effects in the pre-service nurse training, the professional image and code of conduct nurses training, and the geriatric nurse training. At present, there are few studies on the chemotherapeutic drug training of neurologist nurses in China. In clinical work, nurses’ cognitive and practical behaviors of chemotherapeutic drug protection and drug extravasation prevention and treatment are insufficient. It directly harms the health of nursing staff and increases the complications of chemotherapy, increases pain of tumor patients, delays or interrupts chemotherapy, and aggravates the economic burden of patients. Especially, Chemotherapeutic drugs for neuro-oncology have particularity and necessity of urgent training. <strong>Objective:</strong> To investigate the effect of chemotherapeutic drug training through mobile terminal for neuro-oncology nurses based on the Kirkpatrick’s model. <strong>Methods: </strong>The training content and evaluation questionnaire for chemotherapeutic drugs were designed by nursing management personnel and senior nurses in our department according to the guidelines and common diseases requiring chemotherapy in the department. The content includes the basic knowledge of neuro-oncology chemotherapy, pharmacological knowledge, toxic and side effect of chemotherapy, etc., which are regularly pushed through the mobile terminal-WeChat. Forty nurses participated in the training and the effect is evaluated by Kirkpatrick’s model. <strong>Result:</strong> After the training, 100% of nurses were satisfied with the training content and 97.5% with the training form. The scores of nurses in learning level such as basic pharmacological knowledge, drug configuration and exposure, drug treatment and infusion, observation of toxic and side effects, and treatment of drug extravasation were significantly higher than those before the training (P < 0.01). The scores of nurses in the behavior level such as drug allocation, health education, toxic and side effect observation and prediction, treatment of exosmosis, occupational protection were significantly higher than those before the training. After the training, the satisfaction of managers, chemotherapy physicians and chemotherapy patients on the behavior of nurses was significantly higher than that before the training (P < 0.01). <strong>Conclusion:</strong> The chemotherapeutic drug training through mobile terminal based on Kirkpatrick’s model can improve the ability of neuro-oncology nurses, so as to improve the satisfaction of physicians and patients.</span> </div>
基金supported by the National Natural Science Foundation of China (No.81373342)Beijing Natural Science Foundation (Nos.2141004 and 7142114)
文摘The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene expression.RNA interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m RNAs.Therefore,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy.Due to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the co-delivery.In this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.
基金Supported by the Research Grants From the Thailand Research Fund and Khon Kaen University, Thailand Co-first-authors: Nisana Tepsiri and Liengchai Chaturat
文摘AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.
文摘Post-embolization syndrome(PES)is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization.Many strategies have been evaluated to reduce the incidence of PES,but no standard prevention guidelines currently exist.In a single-center,placebo-controlled trial,Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES(from 80%to 6%),of post-procedural liver decompensation(from 14%to 0%),and a shorter hospital stay(4 days vs 6 days),alongside an acceptable safety profile.The results of this study raise several controversial points regarding their applicability in the Western world.In the West,there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis,so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis.Furthermore,in the West,there is a preferred use of drug-eluting beads loaded with doxorubicin,which are associated with a lower incidence of PES.A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.
