In this paper,the preparation and properties of mitomycin C dextran-microspheres(MMC-DMS)were reported.The characteristics of pharmacokinetics and embolization effects of MMC-DMS in vivo were studied in dogs.The avera...In this paper,the preparation and properties of mitomycin C dextran-microspheres(MMC-DMS)were reported.The characteristics of pharmacokinetics and embolization effects of MMC-DMS in vivo were studied in dogs.The average diameter of the microspheres was 75±19μm and the content was 5% of MMC.In in vitro experiment, the release rate of drug demonstrated that the microspheres had sustained-release properties. The microspheres and conventional MMC were infused into the hepatic artery of dogs through a catheter for embolization,respectively.The plasma concentration of MMC was de- termined by HPLC.Results showed that the peak concentration of conventional MMC was 2.6 times as much as MMC-DMS.Angiograms revealed that peripheral blood vessels de- creased obviously in liver.The histopathologic examination showed that the microspheres lodged in the hepatic artery and displayed nodular necrosis in the embolized segment.The MMC-DMS were used in clinical trial in 100 patients with hepatic cancer.The tumor reduc- tion and improvement of symptoms in patients were observed after hepatic arterial embolization.The survival duration was prolonged.Results showed that the MMC-DMS is a promising embolic agent for treatment of hepatic cancer.It could aid in the use of intensive chemotherapy with minimum systemic side effect.展开更多
The preparation and properties of adriamycin magnetic gelatin microspheres(Adr- MG-ms)were reported.The synthesis of magnetic iron oxide ultrafine particle and embolization effects of magnetic gelatin microspheres(MG-...The preparation and properties of adriamycin magnetic gelatin microspheres(Adr- MG-ms)were reported.The synthesis of magnetic iron oxide ultrafine particle and embolization effects of magnetic gelatin microspheres(MG-ms)in dog were studied.Adr- MG-ms consist of 2%(w/w)of adriamycin(Adr)as the core,and 68% of gelatin and 30% of magnetite as the shell with a mean particle size of 22 μm. In vitro experiment,the release rate of drug demonstrated that the microspheres have sustained-release properties.The average diameter of magnetic iron oxide was approximately l0 nm. Transcatheter embolization with MG-ms and  ̄(99m)Tc-labelled MG-ms was performed under external magenet control in dog liver,respectively.Gamma photography and angiogram revealed that MG-ms level was almost equal both in left and right hepatic arteries without magnet,while with magnet(1200 Gs),MG-ms level in left hepatic artery(target site)was about 2.25 fold higher than in right hepatic artery,and few MG-ms in thyroid gland,brain and heart was observed.Results showed that the MG-ms is a promising embolic agent for treatment of hepatic cancer under external magnet control.展开更多
Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to s...Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to study the drug release characteristics ofthe DRAQ-EC-MS.The suspension of DHAQ-EC-MS for clinical liver arterial embolization was prepared.The results show that the DHAQ-EC-MS is regular in morphology with a mean diameter of 110.24 ± 38.19μm and 86.5% of them within the range of 40-150μm,The drug loading is 12.5% and the embedding ratio is 55.6%. The release characteristics were in accordance with the single exponential model.The drug release equation is log(Y∞-Y)=-0.116t-1.198 × 10 ̄(-3)(r=0.9992,t(50)=2.6h).The suspension is ofstable physical and chemical properties and is suitable for clinical use.展开更多
Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin (9-NC ME) for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in term...Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin (9-NC ME) for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1:20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution (P〈0.01). Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.展开更多
Objective: Colorectal cancer is one of the leading causes of cancer related deaths, with recurrence and metasta- sis as the primary reasons for mortality. New evidence has implicated chemokines as the likely cause. We...Objective: Colorectal cancer is one of the leading causes of cancer related deaths, with recurrence and metasta- sis as the primary reasons for mortality. New evidence has implicated chemokines as the likely cause. We studied the positive expression of CXCR4 chemokine receptors in colorectal carcinoma and investigated its correlations to clinicpathological char- acteristics and prognosis. Methods: Tumor tissue specimens of patients with colorectal carcinoma (n = 67) who underwent surgery from January 2003 to December 2004 at the Department of Surgery, Tongji Hospital were collected. CXCR4 expres- sion levels and tumor microvessel density were evaluated by immunohistochemistry. Specimens were immunostained using formalin-fixed, paraffin-embedded tissues. The correlation between the CXCR4 expression and clinicopathological factors was evaluated. Results: In 67 cancer tissue specimens, CXCR4 was positively expressed in 38 cases, positive rate being 56.7%. Positive expression of CXCR4 is associated with an increasing incidence of nodal involvement, higher clinic stage, higher tumor microvessel density and a lower 3-year disease free survival rate as compared to those with negative CXCR4 expression (P < 0.05). Conclusion: Positive CXCR4 expression and high tumor microvessel density are associated with poor prognosis and could be a potential predictive factor for recurrence or metastasis of colorectal cancer patients. So CXCR4 may be a potential target for specific therapeutic interventions in the future.展开更多
Aim To investigate the boundary value problem for second order functional differentiai equations with impulses. Methods The fixed point principle was used to establish our results. Results and Conclusion The results o...Aim To investigate the boundary value problem for second order functional differentiai equations with impulses. Methods The fixed point principle was used to establish our results. Results and Conclusion The results of the esistence, the uniqueness and the continuous dependence on aprameter of soiutions of the boundary value problems for second order functional differential equations with impulses are obtained.展开更多
AIM: To observe the dynamic changes of liver microcirculation in vivo after arterial embolization with degradable starch microspheres (DSM). METHODS: DSM were injected into the proper hepatic artery through a sila...AIM: To observe the dynamic changes of liver microcirculation in vivo after arterial embolization with degradable starch microspheres (DSM). METHODS: DSM were injected into the proper hepatic artery through a silastic tube inserted retrogradely in gastroduodenal artery (GDA) of SD rats. Fluorescent microscopy was used to evaluate the dynamic changes of blood flow through the terminal portal venules (TPVs), sinusoids and terminal hepatic venules (THVs). The movements of DSM debris were also recorded. Six hours after injection of DSM, percentages of THVs with completely stagnant blood flow were recorded. RESULTS: Two phases of blood flow change were recorded. In phase one: after intra-arterial injection of DSM, slow or stagnant blood flow was immediately recorded in TPVs, sinusoids and THVs. This change was reversible, and blood flow resumed completely. In phase two: after phase one, blood flow in TPVs changed again and three patterns of blood flow were recorded. Six hours after DSM injection, 36.9% ± 9.2% of THVs were found with completely stagnant blood flow. CONCLUSION: DSM can stop the microcirculatory blood flow in some areas of liver parenchyma. Liver parenchyma supplied by arteries with larger A-P shunt is considered at a higher risk of total microcirculatory blood stagnation after injection of DSM through hepatic artery.展开更多
A lattice Boltzmann model of two dimensions is used to simulate the movement of a single rigid particle suspended in a pulsating flow in micro vessel The particle is as big as a red blood cell, and the micro vessel is...A lattice Boltzmann model of two dimensions is used to simulate the movement of a single rigid particle suspended in a pulsating flow in micro vessel The particle is as big as a red blood cell, and the micro vessel is four times as wide as the diameter of the particle. It is found that Segrd-Silberberg effect will not respond to the pulsation of the flow when the Reynolds number is relatively high. However, when the Reynolds number is low enough, Segrd-Silberberg effect disappears. In the steady flow, different initial position leads to different equilibrium positions. In a pulsating flow, different frequencies of pulsation also cause different equilibrium positions. Particularly, when the frequency of pulsation is closed to the human heart rate, Segrd-Silberberg effect presents again. The evolutions of velocity, rotation, and trajectory of the particle are investigated to find the dynamics of such abnormal phenomenon.展开更多
5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmacon...5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed.展开更多
文摘In this paper,the preparation and properties of mitomycin C dextran-microspheres(MMC-DMS)were reported.The characteristics of pharmacokinetics and embolization effects of MMC-DMS in vivo were studied in dogs.The average diameter of the microspheres was 75±19μm and the content was 5% of MMC.In in vitro experiment, the release rate of drug demonstrated that the microspheres had sustained-release properties. The microspheres and conventional MMC were infused into the hepatic artery of dogs through a catheter for embolization,respectively.The plasma concentration of MMC was de- termined by HPLC.Results showed that the peak concentration of conventional MMC was 2.6 times as much as MMC-DMS.Angiograms revealed that peripheral blood vessels de- creased obviously in liver.The histopathologic examination showed that the microspheres lodged in the hepatic artery and displayed nodular necrosis in the embolized segment.The MMC-DMS were used in clinical trial in 100 patients with hepatic cancer.The tumor reduc- tion and improvement of symptoms in patients were observed after hepatic arterial embolization.The survival duration was prolonged.Results showed that the MMC-DMS is a promising embolic agent for treatment of hepatic cancer.It could aid in the use of intensive chemotherapy with minimum systemic side effect.
文摘The preparation and properties of adriamycin magnetic gelatin microspheres(Adr- MG-ms)were reported.The synthesis of magnetic iron oxide ultrafine particle and embolization effects of magnetic gelatin microspheres(MG-ms)in dog were studied.Adr- MG-ms consist of 2%(w/w)of adriamycin(Adr)as the core,and 68% of gelatin and 30% of magnetite as the shell with a mean particle size of 22 μm. In vitro experiment,the release rate of drug demonstrated that the microspheres have sustained-release properties.The average diameter of magnetic iron oxide was approximately l0 nm. Transcatheter embolization with MG-ms and  ̄(99m)Tc-labelled MG-ms was performed under external magenet control in dog liver,respectively.Gamma photography and angiogram revealed that MG-ms level was almost equal both in left and right hepatic arteries without magnet,while with magnet(1200 Gs),MG-ms level in left hepatic artery(target site)was about 2.25 fold higher than in right hepatic artery,and few MG-ms in thyroid gland,brain and heart was observed.Results showed that the MG-ms is a promising embolic agent for treatment of hepatic cancer under external magnet control.
文摘Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to study the drug release characteristics ofthe DRAQ-EC-MS.The suspension of DHAQ-EC-MS for clinical liver arterial embolization was prepared.The results show that the DHAQ-EC-MS is regular in morphology with a mean diameter of 110.24 ± 38.19μm and 86.5% of them within the range of 40-150μm,The drug loading is 12.5% and the embedding ratio is 55.6%. The release characteristics were in accordance with the single exponential model.The drug release equation is log(Y∞-Y)=-0.116t-1.198 × 10 ̄(-3)(r=0.9992,t(50)=2.6h).The suspension is ofstable physical and chemical properties and is suitable for clinical use.
基金National Natural Science Foundation of China (GrantNo.30430760)the 985 projects (Phase II) of the State Key Labo-ratory of Natural and Biomimetic Drugs (Peking University, China).
文摘Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin (9-NC ME) for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1:20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution (P〈0.01). Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.
文摘Objective: Colorectal cancer is one of the leading causes of cancer related deaths, with recurrence and metasta- sis as the primary reasons for mortality. New evidence has implicated chemokines as the likely cause. We studied the positive expression of CXCR4 chemokine receptors in colorectal carcinoma and investigated its correlations to clinicpathological char- acteristics and prognosis. Methods: Tumor tissue specimens of patients with colorectal carcinoma (n = 67) who underwent surgery from January 2003 to December 2004 at the Department of Surgery, Tongji Hospital were collected. CXCR4 expres- sion levels and tumor microvessel density were evaluated by immunohistochemistry. Specimens were immunostained using formalin-fixed, paraffin-embedded tissues. The correlation between the CXCR4 expression and clinicopathological factors was evaluated. Results: In 67 cancer tissue specimens, CXCR4 was positively expressed in 38 cases, positive rate being 56.7%. Positive expression of CXCR4 is associated with an increasing incidence of nodal involvement, higher clinic stage, higher tumor microvessel density and a lower 3-year disease free survival rate as compared to those with negative CXCR4 expression (P < 0.05). Conclusion: Positive CXCR4 expression and high tumor microvessel density are associated with poor prognosis and could be a potential predictive factor for recurrence or metastasis of colorectal cancer patients. So CXCR4 may be a potential target for specific therapeutic interventions in the future.
文摘Aim To investigate the boundary value problem for second order functional differentiai equations with impulses. Methods The fixed point principle was used to establish our results. Results and Conclusion The results of the esistence, the uniqueness and the continuous dependence on aprameter of soiutions of the boundary value problems for second order functional differential equations with impulses are obtained.
文摘AIM: To observe the dynamic changes of liver microcirculation in vivo after arterial embolization with degradable starch microspheres (DSM). METHODS: DSM were injected into the proper hepatic artery through a silastic tube inserted retrogradely in gastroduodenal artery (GDA) of SD rats. Fluorescent microscopy was used to evaluate the dynamic changes of blood flow through the terminal portal venules (TPVs), sinusoids and terminal hepatic venules (THVs). The movements of DSM debris were also recorded. Six hours after injection of DSM, percentages of THVs with completely stagnant blood flow were recorded. RESULTS: Two phases of blood flow change were recorded. In phase one: after intra-arterial injection of DSM, slow or stagnant blood flow was immediately recorded in TPVs, sinusoids and THVs. This change was reversible, and blood flow resumed completely. In phase two: after phase one, blood flow in TPVs changed again and three patterns of blood flow were recorded. Six hours after DSM injection, 36.9% ± 9.2% of THVs were found with completely stagnant blood flow. CONCLUSION: DSM can stop the microcirculatory blood flow in some areas of liver parenchyma. Liver parenchyma supplied by arteries with larger A-P shunt is considered at a higher risk of total microcirculatory blood stagnation after injection of DSM through hepatic artery.
基金Supported by the National Natural Science Foundation of China under Grant Nos.10747004,11065006,and 81060307
文摘A lattice Boltzmann model of two dimensions is used to simulate the movement of a single rigid particle suspended in a pulsating flow in micro vessel The particle is as big as a red blood cell, and the micro vessel is four times as wide as the diameter of the particle. It is found that Segrd-Silberberg effect will not respond to the pulsation of the flow when the Reynolds number is relatively high. However, when the Reynolds number is low enough, Segrd-Silberberg effect disappears. In the steady flow, different initial position leads to different equilibrium positions. In a pulsating flow, different frequencies of pulsation also cause different equilibrium positions. Particularly, when the frequency of pulsation is closed to the human heart rate, Segrd-Silberberg effect presents again. The evolutions of velocity, rotation, and trajectory of the particle are investigated to find the dynamics of such abnormal phenomenon.
文摘5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed.