Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regime...Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.展开更多
OBJECTIVE To estimate effects, survival rate after the short-time efficacy, side the treatment of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine （HCPT） for the patients ...OBJECTIVE To estimate effects, survival rate after the short-time efficacy, side the treatment of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine （HCPT） for the patients with advanced colorectal cancer. METHODS From January 2002 to November 2005, 59 patients with advanced colorectal cancer confirmed by pathology were enrolled into this study in the department of medical oncology, in the Sixth People＇s Hospital of Shanghai Jiaotong University, Shanghai. Patients＇ characteristics in two groups were similarly confirmed by statistic. All 37 patients in OH group received oxalip21atin （130 mg/m^2 d1） plus hydroxycamptothecine （6 mg/m d1-4）, and all 22 patients in the HLF group received hydroxycamptothecine （6 mg/m^2 d1-4） plus leucovorin （300 mg d1-5） and 5-fluorouracil （0.375 g/m^2 d1-5）. The regimens in both groups were 21-day cycle that was repeated three weeks. The side effects were evaluated. The efficacy was estimated after two cycles of chemotherapy for each patient. RESULTS The efficacy of the treatment in the OH group with 37 patients and in the HLF group with 22 patients was estimated. The overall response rate （CR ＋ PR） was 32.4% in the OH group and 22.7% in the HLF group. There was no complete response （CR） and there was no statistical significantly difference （%2= 0.876, P = 0.704） in two groups. The 1-year survival rate was 30.98% in the OH group and 15.02% in the HLF group, and it had no significant difference between the two groups. The median PSF and OS were 5.83 months and 11.17 months in the OH group vs. 7.40 months and 10.48 months in the HLF group, and it had no significant differences between the two groups （P 〉 0.05）. The major side effects of grade III and IV in the two groups were myelosuppression and gastrointestinal reactions. The statistically significant difference in side effects appeared in leukopenia （χ^2= 17.173, P = 0.001）, nausea/vomiting （χ^2= 6.426, P = 0.039）, diarrhea （χ^2= 16.245, P = 0.000） and peripheral neuropathy. CONCLUSION The efficacy was almost equal between the OH and the HLF groups, and the two regimens can be used as the second-line treatments for the patients with colorectal cancer. Leucopenia, nausea, diarrhea and peripheral neuropathy appeared more in OH group, and anemia and thrombocytopenia were almost equal between the OH and the HLF groups.展开更多
5-fluarouracil-based chemotherapy has become a standard regimen for the treatment of advanced colorectal cancer （ACRC）.^1 Defined as the second line therapy for ACRC with 5-fluarouracil （5-Fu） plus leucovorin （LV...5-fluarouracil-based chemotherapy has become a standard regimen for the treatment of advanced colorectal cancer （ACRC）.^1 Defined as the second line therapy for ACRC with 5-fluarouracil （5-Fu） plus leucovorin （LV） combined with oxaliplatin （OXA）, the response rate （RR）, progression-free survival （PFS） and overall survival （OS） were 21.2%, at 4.7 and 11.5 months, whereas RR, PFS and OS with 5-Fu plus LV combined with irinotecan （CPT-11） were 11.4%, at 3.2 and 12.2 months. There were no statistical difference between the two protocals.^2,3 Those results may well suggest that some of these patients were resistant to 5-Fu. Therefore it is necessary to find a more effective regimen without 5-Fu to treat recurrent ACRC patients that were initially treated with 5-Fu. Our previous study showed that OXA can enhance the function of hydroxycamptothecine （HCPT） in inducing the apoptosis of a human colorectal cell line in vivo.^4 So we chose OXA plus HCPT （OH） regimen to treat 28 patients with ACRC and compared RR, one-year survival rate, PFS, OS and main toxicities with a 5-Fu plus LV combined with OXA （OFL） regimen.展开更多
Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or ...Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or advanced hepatocellular carcinoma. The results demonstrate a partial remissionrate of 54. 2%, significantly higher than that in embolization with chemotherapeutic agents alone (cis-platin, adriamycin and mitomycin, 32. 1%, P<O. 01) . Morever, the adverse reactions of hydroxycamp-tothecine and cantharidin, when applied systemically, including hematuria or urodynia were successfullyeliminated.展开更多
Camptothecine （CPT） and hydroxycamptothecin （HCPT）, two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as th...Camptothecine （CPT） and hydroxycamptothecin （HCPT）, two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as the ratio of material to liquid, ethanol concentration, and homogenate time. The optimum technology parameters for homogenate extraction of CPT and HCPT from C acuminata leaves were determined as homogenate time at 8 rain, ethanol concentration at 55% and the ratio of material to liquid at 1：15 （g：mL）. By using the optimized parameters, we obtained 0.639‰ extraction rate for CPT and 0.437‰ for HCPT. The extraction yields of CPT and HCPT extracted by homogenating technology were higher than those by other extractive methods, such as ultrasonic, reflux, shaking in water bath. It is concluded that the homogenate extraction technology was an efficient method for extracting CPT and HCPT from C acuminata leaves, with characteristics of less extraction time and high yield.展开更多
The determination method of 10-hydroxycamptothecin in Camptotheca acuminata fruits by high-performance liquid chromatogram (HPLC) was studied. The HPLC analysis was performed on a HIQ sil C18(4.6×250 mm) column w...The determination method of 10-hydroxycamptothecin in Camptotheca acuminata fruits by high-performance liquid chromatogram (HPLC) was studied. The HPLC analysis was performed on a HIQ sil C18(4.6×250 mm) column with mobile phase of acetonitrilewater (3:7, V:V), flow rate 1 mLmin-1 and UV detective wavelength 266 nm. Extracting 10-hydroxycamptothecin by ultrasonic method from fruits of C. acuminata to prepare samples for analysis was systematically discussed. The optimal extraction condition was carried out by 60% alcohol solution at 60℃ for 50 minutes.展开更多
AIM To study the effects of arsenic trioxide andHCPT on different degrees of differentiated gastriccancer cells（SGC-7901,MKN-45,MKN-28）withrespect to both cytotoxicity and induction ofapoptosis in vitro.METHODS The ...AIM To study the effects of arsenic trioxide andHCPT on different degrees of differentiated gastriccancer cells（SGC-7901,MKN-45,MKN-28）withrespect to both cytotoxicity and induction ofapoptosis in vitro.METHODS The cytotoxicity of As<sub>2</sub>O<sub>3</sub> and HCPTon gastric cancer cells was determined by MTTassay.Morphologic changes of apoptosis ofgastric cancer cells were observed by lightmicroscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancercells induced by HCPT and As<sub>2</sub>O<sub>3</sub> were investigatedby TUNEL method and flow cytometry.RESULTS As<sub>2</sub>O<sub>3</sub> and HCPT had remarkablecytotoxic effects on different degrees ofdifferentiated gastric cancer cells.The IC<sub>50</sub>ofAs<sub>2</sub>O<sub>3</sub> on well differentiated gastric cancer cellMKN-28,moderately differentiated gastric cancercell SGC-7901,and poorly differentiated gastriccancer cell MKN-28 were 8.91 μmol/L,10.57μmol/L,and 11.65 μmol/L,respectively.The IC<sub>50</sub>of HCPT on MKN-28,SGC-7901,and MKN-45 were9.35 mg/L,10.21 mg/L,and 12.63 mg/Lrespectively after 48 h treatment.After 12 h ofexposure to both drugs,gastric cancer cellsexhibited morphologic features of apoptosis,including cell shrinkage,nuclear condensation, and formation of apoptotic bodies.A typicalsubdiploid peak before G<sub>0</sub>/G<sub>1</sub> phase was observedby flow cytometry.The apoptotic rates of SGC-7901,MKN-45,and MKN-28 were 13.84%,22.52%,and 9.68%,respectively after 48 hexposure to 10 μmol/L As<sub>2</sub>O<sub>3</sub>.The apoptotic ratesof SGC-7901,MKN-45,and MKN-28 were 21.88%,12.35%,and 30.26%,respectively after 48 hexposure to 10 mg/L HCPT.The apoptotic indicewere 7%-15% as assessed by TUNEL method.The effect of As<sub>2</sub>O<sub>3</sub> on SGC-7901 showedremarkable cell cycle specificity,which inducedcell death in G<sub>1</sub> phase,and blocked G<sub>2</sub>/M phase.HCPT also showed a remarkable cell cyclespecificity,by inducing cell death and apoptosis inG<sub>1</sub> phase and arrest of proliferation at S phase.CONCLUSION As<sub>2</sub>O<sub>3</sub> and HCPT exhibitsignificant cytotoxicity on gastric cancer cells byinduction of apoptosis.As<sub>2</sub>O<sub>3</sub> and HCPT mighthave a promising prospect in the treatment ofgastric cancer,which needs to be further studied.展开更多
AIM. To establish a kind of standardization of the clinical chemotherapeutic prototypes for unresectable hepatocellular carcinomas （HCC）. METHODS： 10-Hydroxycamptothecin （HCPT） was applied through transcatheter a...AIM. To establish a kind of standardization of the clinical chemotherapeutic prototypes for unresectable hepatocellular carcinomas （HCC）. METHODS： 10-Hydroxycamptothecin （HCPT） was applied through transcatheter arterial embolization （TAE） to HCC patients who were categorized into three groups： （1） test group： treatment with HCPT twice （HCPT dl and 14） through TAE and portal venous embolization. （2） Control Ⅰ： treatment with anticancer drugs without HCPT. （3） Control Ⅱ： treatment with HCPT as a major component in anticancer drugs once （HCPT dl）. A set of comparisons between test groups and control Ⅰ and Ⅱ groups were performed before and after the treatment to study the effectiveness of each treatment, in terms of tumor volumes, dynamic variations in serum alpha-fetoprotein （AFP）, gamma-glutamyl transferase hepatoma-specific band （GGT-Ⅱ）, patient survival and adverse events. RESULTS： The general effectiveness rate of the test group reached 62.1% （72/116）, remarkably higher than that of control Ⅰ （32.1%, 40/124） and control Ⅱ （54.7%, 47/56）, （P〈0.01 and P〈0.05, respectively）. Especially, the reduction rate or disappearance of the portal vein tumor emboli was as high as 88.4% （61/69） in the test group, in contrast with 13.9% （10/72） in control Ⅰ and 35.9% （18/51） in control Ⅱ （P〈0.01 and P〈0.01, respectively）. After treatment, AFP decreased or turned to negative levels at 52.3% （34/65） in control Ⅰ, 67.3% （35/52） in control Ⅱ, and 96.8% （60/62） in the test group. Also GGT-Ⅱ declined or became negative at 37.8% （28/74） in control Ⅰ, 69.5% （57/82） in control Ⅱ, and 94.7% （89/94） in test group （P〈0.01 and P〈0.05, respectively）. CONCLUSION： We have designed a good protocol （test group） to treat HCC with excellent advantages of high efficiency, low cost, low toxicity and low adverse events and easy application. It could be recommended as one of the standardizations for HCC treatment in clinical practice.展开更多
The improved 3 step preparation of a key antitumor agent, 7 ethyl 10 hydroxycamptothecin(SN 38), which consists of ethylation, oxidation and photo chemical rearrangement, is described. The proposed reaction mech...The improved 3 step preparation of a key antitumor agent, 7 ethyl 10 hydroxycamptothecin(SN 38), which consists of ethylation, oxidation and photo chemical rearrangement, is described. The proposed reaction mechanism is also discussed.展开更多
Objective： Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment. The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment...Objective： Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment. The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment. It has been reported that in vitro and in vivo hyperthermia enhanced the cytotoxic effect of certain anticancer drugs. However, this enhancement varies, depending on the drug used and the scheduling of treatments. Thus, the combination effect of chemotherapy and hyperthermia remains unclear. In this study, we aimed to investigate whether concurrent exposure of human hepatocellular carcinoma cells SMMC-7721 to chemotherapeutic agents andhyperthermia could increase anticancer effects. Methods ： Two chemotherapeutic agents, cisplatin and hydroxycamptothecin, were applied. The MTT assay was performed to evaluate the growth inhibition of SMMC-7721 induced by anticancer drugs with and without hyperthermia. Flow cytometric analysis was used for the assessment of apoptosis after treatments. Results： The percentages of growth inhibition of SMMC-7721 induced by cisplatin （10μg/ml） alone, hydroxycamptothecin （1μg/ml）alone, hyperthermia alone, cisplatin and hyperthermia, hydroxycamptothecin and hyperthermia, were 20.77%, 13.65%, 32.46%, 62.76%, 71.89%, respectively. The percentages of apoptosis of five treatments are 5.56%, 3.96%, 10.16%, 24.32%, 20.42%, respectively. Conclusion： While both hyperthermia and anticancer drugs can individually induce apoptosis and anti-proliferation effect, the combination of the two treatments induce significantly higher apoptosis and cytotoxicity than hyperthermia or anticancer drugs treatment alone. These data suggest a synergistic benefit when hyperthermia and anticancer drugs used concurrently.展开更多
Camptothecine(CPT) and hydroxycamptothecin(HCPT), two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as the rati...Camptothecine(CPT) and hydroxycamptothecin(HCPT), two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as the ratio of material to liquid, ethanol concentration, and homogenate time.The optimum technology parameters for homogenate extraction of CPT and HCPT from C.acuminata leaves were determined as homogenate time at 8 min, ethanol concentration at 55% and the ratio of material to liquid at 1:15(g:mL).By using the optimized parameters, we obtained 0.639‰ extraction rate for CPT and 0.437‰ for HCPT.The extraction yields of CPT and HCPT extracted by homogenating technology were higher than those by other extractive methods, such as ultrasonic, reflux, shaking in water bath.It is concluded that the homogenate extraction technology was an efficient method for extracting CPT and HCPT from C.acuminata leaves, with characteristics of less extraction time and high yield.展开更多
Objective: To evaluate the therapeutic as well as side effects of hydroxycamptothecin (HCPT) plus FOLFOX4 regimen as salvage therapy for patients with advanced gastric cancer. Methods: A total of 19 patients with adva...Objective: To evaluate the therapeutic as well as side effects of hydroxycamptothecin (HCPT) plus FOLFOX4 regimen as salvage therapy for patients with advanced gastric cancer. Methods: A total of 19 patients with advanced gastric cancer received HCPT plus FOLFOX4 as salvage therapy, in detail, Oxaliplatin 85 mg/m2 was given intravenously on day 1, CF 200 mg/m2, 5-Fu 400 mg/m2 given in bolus immediately after CF, days 1-2; 5-Fu 600 mg/m2 given continuously after bolus for 22 h on day 1, day 2, HCPT given intravenously at dosage of 10 mg/m2 on days 1-2. Therapeutic effects were evaluated at least after two cycles of treatment. Results: 17 cases among the 19 patients were valid for response evaluation, with CR 1 , PR 6, SD 4, PD 6. The response rate was 41.2%. For the 12 patients with liver metastasis, response rate of the liver foci was 50%. The main toxicities were bone marrow suppression, nausea and vomiting, and peripheral neuropathy; there were no chemotherapy-related deaths. Conclusion: The combination regimen with HCPT plus FOFLOX4 regimen was effective as salvage therapy for patients with advanced gastric cancer, with particularly high response rate for liver metastasis, and the side effects were tolerable and manageable.展开更多
Hydroxycamptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro. This is the first study to investigate the release, distribution, and efficacy of hydroxycamptothecin...Hydroxycamptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro. This is the first study to investigate the release, distribution, and efficacy of hydroxycamptothecin which was incorporated into the biodegradable polymer Polylactic Acid (PLA), and implant into brain directly. In vitro release curve generated showed that a large initial release occurred over the first three days and was followed by a steady, but considerably slower rate of release over the next 25 days. After implanting the discs into 40 male SD rats, the animals were followed up to 28 days, where the concentration in brain tissue was far higher than that in peripheral blood at the each of the eight time-points evaluated, and it was also within the therapeutic range for C6 cells tested in vitro. The in vivoefficacy of the discs was evaluated with rats inoculated intracranially with C6 glioma and treated with hydroxycamptothecin polymer compared to intravenous as well as intratumoral injections;the median survival is 21.1, 13.9, 14.9 days, respectively. Given these data, we conclude that the biodegradable polymer PLA releases hydroxycamptothecin, producing tumoricidal levels in brain tissues and prolonging survival in a rat glioma model.展开更多
Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in th...Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in the bladder are observed in some patients. There are numerous reports of trials of intravesical instillation of anticancer agents with the objective of lowering this recurrence rate. The aim of this study was to compare the prophylactic efficacy and safety of epirubicin （EPI）, pirarubicin （THP） and hydroxycamptothecin （HCPT） in superficial bladder cancer.Methods This study enrolled a total of 189 patients who had been diagnosed with superficial bladder cancer during the period from 2004 through 2007 at Beijing Friendship Hospital. All patients were randomly allocated to one of three treatment groups. Patients in group A received 29 doses of EPI 30 mg/30 ml, patients in group B received 29 doses of THP 30 mg/30 ml, and patients in group C received 29 doses of HCPT 30 mg/30 ml, over a period of 24 months.Results The recurrence-free rate in the 2 anthracycline treatment groups （A and B） were significantly better than that of the HCPT treatment group. In the safety evaluation, the incidences of pollakiuria, pain on urination, dysuria, hematuria,and contracted bladder were not significantly different between groups A and B, but some were significantly higher in groups A and B than that in group C.Conclusion The efficacy of EPI and THP was significantly better than HCPT in the prevention of bladder cancer recurrence.展开更多
文摘Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.
文摘OBJECTIVE To estimate effects, survival rate after the short-time efficacy, side the treatment of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine （HCPT） for the patients with advanced colorectal cancer. METHODS From January 2002 to November 2005, 59 patients with advanced colorectal cancer confirmed by pathology were enrolled into this study in the department of medical oncology, in the Sixth People＇s Hospital of Shanghai Jiaotong University, Shanghai. Patients＇ characteristics in two groups were similarly confirmed by statistic. All 37 patients in OH group received oxalip21atin （130 mg/m^2 d1） plus hydroxycamptothecine （6 mg/m d1-4）, and all 22 patients in the HLF group received hydroxycamptothecine （6 mg/m^2 d1-4） plus leucovorin （300 mg d1-5） and 5-fluorouracil （0.375 g/m^2 d1-5）. The regimens in both groups were 21-day cycle that was repeated three weeks. The side effects were evaluated. The efficacy was estimated after two cycles of chemotherapy for each patient. RESULTS The efficacy of the treatment in the OH group with 37 patients and in the HLF group with 22 patients was estimated. The overall response rate （CR ＋ PR） was 32.4% in the OH group and 22.7% in the HLF group. There was no complete response （CR） and there was no statistical significantly difference （%2= 0.876, P = 0.704） in two groups. The 1-year survival rate was 30.98% in the OH group and 15.02% in the HLF group, and it had no significant difference between the two groups. The median PSF and OS were 5.83 months and 11.17 months in the OH group vs. 7.40 months and 10.48 months in the HLF group, and it had no significant differences between the two groups （P 〉 0.05）. The major side effects of grade III and IV in the two groups were myelosuppression and gastrointestinal reactions. The statistically significant difference in side effects appeared in leukopenia （χ^2= 17.173, P = 0.001）, nausea/vomiting （χ^2= 6.426, P = 0.039）, diarrhea （χ^2= 16.245, P = 0.000） and peripheral neuropathy. CONCLUSION The efficacy was almost equal between the OH and the HLF groups, and the two regimens can be used as the second-line treatments for the patients with colorectal cancer. Leucopenia, nausea, diarrhea and peripheral neuropathy appeared more in OH group, and anemia and thrombocytopenia were almost equal between the OH and the HLF groups.
文摘5-fluarouracil-based chemotherapy has become a standard regimen for the treatment of advanced colorectal cancer （ACRC）.^1 Defined as the second line therapy for ACRC with 5-fluarouracil （5-Fu） plus leucovorin （LV） combined with oxaliplatin （OXA）, the response rate （RR）, progression-free survival （PFS） and overall survival （OS） were 21.2%, at 4.7 and 11.5 months, whereas RR, PFS and OS with 5-Fu plus LV combined with irinotecan （CPT-11） were 11.4%, at 3.2 and 12.2 months. There were no statistical difference between the two protocals.^2,3 Those results may well suggest that some of these patients were resistant to 5-Fu. Therefore it is necessary to find a more effective regimen without 5-Fu to treat recurrent ACRC patients that were initially treated with 5-Fu. Our previous study showed that OXA can enhance the function of hydroxycamptothecine （HCPT） in inducing the apoptosis of a human colorectal cell line in vivo.^4 So we chose OXA plus HCPT （OH） regimen to treat 28 patients with ACRC and compared RR, one-year survival rate, PFS, OS and main toxicities with a 5-Fu plus LV combined with OXA （OFL） regimen.
文摘Transcatheter arterial embolization with hydroxycamptothecine, cantharidin and cisplatin,thoroughly mixed with large doses of interferon and interleukin-2, was performed in 48 cases with unre-sectable intermediate or advanced hepatocellular carcinoma. The results demonstrate a partial remissionrate of 54. 2%, significantly higher than that in embolization with chemotherapeutic agents alone (cis-platin, adriamycin and mitomycin, 32. 1%, P<O. 01) . Morever, the adverse reactions of hydroxycamp-tothecine and cantharidin, when applied systemically, including hematuria or urodynia were successfullyeliminated.
文摘Camptothecine （CPT） and hydroxycamptothecin （HCPT）, two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as the ratio of material to liquid, ethanol concentration, and homogenate time. The optimum technology parameters for homogenate extraction of CPT and HCPT from C acuminata leaves were determined as homogenate time at 8 rain, ethanol concentration at 55% and the ratio of material to liquid at 1：15 （g：mL）. By using the optimized parameters, we obtained 0.639‰ extraction rate for CPT and 0.437‰ for HCPT. The extraction yields of CPT and HCPT extracted by homogenating technology were higher than those by other extractive methods, such as ultrasonic, reflux, shaking in water bath. It is concluded that the homogenate extraction technology was an efficient method for extracting CPT and HCPT from C acuminata leaves, with characteristics of less extraction time and high yield.
基金This paper was supported by National Natural Science Foundation of China (No. 30070086).
文摘The determination method of 10-hydroxycamptothecin in Camptotheca acuminata fruits by high-performance liquid chromatogram (HPLC) was studied. The HPLC analysis was performed on a HIQ sil C18(4.6×250 mm) column with mobile phase of acetonitrilewater (3:7, V:V), flow rate 1 mLmin-1 and UV detective wavelength 266 nm. Extracting 10-hydroxycamptothecin by ultrasonic method from fruits of C. acuminata to prepare samples for analysis was systematically discussed. The optimal extraction condition was carried out by 60% alcohol solution at 60℃ for 50 minutes.
基金the Natural Science Foundation of Committee of Science and Technology of Shanghai Municipality(№964119035)
文摘AIM To study the effects of arsenic trioxide andHCPT on different degrees of differentiated gastriccancer cells（SGC-7901,MKN-45,MKN-28）withrespect to both cytotoxicity and induction ofapoptosis in vitro.METHODS The cytotoxicity of As<sub>2</sub>O<sub>3</sub> and HCPTon gastric cancer cells was determined by MTTassay.Morphologic changes of apoptosis ofgastric cancer cells were observed by lightmicroscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancercells induced by HCPT and As<sub>2</sub>O<sub>3</sub> were investigatedby TUNEL method and flow cytometry.RESULTS As<sub>2</sub>O<sub>3</sub> and HCPT had remarkablecytotoxic effects on different degrees ofdifferentiated gastric cancer cells.The IC<sub>50</sub>ofAs<sub>2</sub>O<sub>3</sub> on well differentiated gastric cancer cellMKN-28,moderately differentiated gastric cancercell SGC-7901,and poorly differentiated gastriccancer cell MKN-28 were 8.91 μmol/L,10.57μmol/L,and 11.65 μmol/L,respectively.The IC<sub>50</sub>of HCPT on MKN-28,SGC-7901,and MKN-45 were9.35 mg/L,10.21 mg/L,and 12.63 mg/Lrespectively after 48 h treatment.After 12 h ofexposure to both drugs,gastric cancer cellsexhibited morphologic features of apoptosis,including cell shrinkage,nuclear condensation, and formation of apoptotic bodies.A typicalsubdiploid peak before G<sub>0</sub>/G<sub>1</sub> phase was observedby flow cytometry.The apoptotic rates of SGC-7901,MKN-45,and MKN-28 were 13.84%,22.52%,and 9.68%,respectively after 48 hexposure to 10 μmol/L As<sub>2</sub>O<sub>3</sub>.The apoptotic ratesof SGC-7901,MKN-45,and MKN-28 were 21.88%,12.35%,and 30.26%,respectively after 48 hexposure to 10 mg/L HCPT.The apoptotic indicewere 7%-15% as assessed by TUNEL method.The effect of As<sub>2</sub>O<sub>3</sub> on SGC-7901 showedremarkable cell cycle specificity,which inducedcell death in G<sub>1</sub> phase,and blocked G<sub>2</sub>/M phase.HCPT also showed a remarkable cell cyclespecificity,by inducing cell death and apoptosis inG<sub>1</sub> phase and arrest of proliferation at S phase.CONCLUSION As<sub>2</sub>O<sub>3</sub> and HCPT exhibitsignificant cytotoxicity on gastric cancer cells byinduction of apoptosis.As<sub>2</sub>O<sub>3</sub> and HCPT mighthave a promising prospect in the treatment ofgastric cancer,which needs to be further studied.
文摘AIM. To establish a kind of standardization of the clinical chemotherapeutic prototypes for unresectable hepatocellular carcinomas （HCC）. METHODS： 10-Hydroxycamptothecin （HCPT） was applied through transcatheter arterial embolization （TAE） to HCC patients who were categorized into three groups： （1） test group： treatment with HCPT twice （HCPT dl and 14） through TAE and portal venous embolization. （2） Control Ⅰ： treatment with anticancer drugs without HCPT. （3） Control Ⅱ： treatment with HCPT as a major component in anticancer drugs once （HCPT dl）. A set of comparisons between test groups and control Ⅰ and Ⅱ groups were performed before and after the treatment to study the effectiveness of each treatment, in terms of tumor volumes, dynamic variations in serum alpha-fetoprotein （AFP）, gamma-glutamyl transferase hepatoma-specific band （GGT-Ⅱ）, patient survival and adverse events. RESULTS： The general effectiveness rate of the test group reached 62.1% （72/116）, remarkably higher than that of control Ⅰ （32.1%, 40/124） and control Ⅱ （54.7%, 47/56）, （P〈0.01 and P〈0.05, respectively）. Especially, the reduction rate or disappearance of the portal vein tumor emboli was as high as 88.4% （61/69） in the test group, in contrast with 13.9% （10/72） in control Ⅰ and 35.9% （18/51） in control Ⅱ （P〈0.01 and P〈0.01, respectively）. After treatment, AFP decreased or turned to negative levels at 52.3% （34/65） in control Ⅰ, 67.3% （35/52） in control Ⅱ, and 96.8% （60/62） in the test group. Also GGT-Ⅱ declined or became negative at 37.8% （28/74） in control Ⅰ, 69.5% （57/82） in control Ⅱ, and 94.7% （89/94） in test group （P〈0.01 and P〈0.05, respectively）. CONCLUSION： We have designed a good protocol （test group） to treat HCC with excellent advantages of high efficiency, low cost, low toxicity and low adverse events and easy application. It could be recommended as one of the standardizations for HCC treatment in clinical practice.
文摘The improved 3 step preparation of a key antitumor agent, 7 ethyl 10 hydroxycamptothecin(SN 38), which consists of ethylation, oxidation and photo chemical rearrangement, is described. The proposed reaction mechanism is also discussed.
文摘Objective： Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment. The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment. It has been reported that in vitro and in vivo hyperthermia enhanced the cytotoxic effect of certain anticancer drugs. However, this enhancement varies, depending on the drug used and the scheduling of treatments. Thus, the combination effect of chemotherapy and hyperthermia remains unclear. In this study, we aimed to investigate whether concurrent exposure of human hepatocellular carcinoma cells SMMC-7721 to chemotherapeutic agents andhyperthermia could increase anticancer effects. Methods ： Two chemotherapeutic agents, cisplatin and hydroxycamptothecin, were applied. The MTT assay was performed to evaluate the growth inhibition of SMMC-7721 induced by anticancer drugs with and without hyperthermia. Flow cytometric analysis was used for the assessment of apoptosis after treatments. Results： The percentages of growth inhibition of SMMC-7721 induced by cisplatin （10μg/ml） alone, hydroxycamptothecin （1μg/ml）alone, hyperthermia alone, cisplatin and hyperthermia, hydroxycamptothecin and hyperthermia, were 20.77%, 13.65%, 32.46%, 62.76%, 71.89%, respectively. The percentages of apoptosis of five treatments are 5.56%, 3.96%, 10.16%, 24.32%, 20.42%, respectively. Conclusion： While both hyperthermia and anticancer drugs can individually induce apoptosis and anti-proliferation effect, the combination of the two treatments induce significantly higher apoptosis and cytotoxicity than hyperthermia or anticancer drugs treatment alone. These data suggest a synergistic benefit when hyperthermia and anticancer drugs used concurrently.
基金supported by National Key Tech-nology R & D Program (grant no. 2006BAD18B04).
文摘Camptothecine(CPT) and hydroxycamptothecin(HCPT), two kinds of anti-cancer alkaloids, were extracted from Camptotheca acuminata leaves using homogenate extraction technology under different conditions such as the ratio of material to liquid, ethanol concentration, and homogenate time.The optimum technology parameters for homogenate extraction of CPT and HCPT from C.acuminata leaves were determined as homogenate time at 8 min, ethanol concentration at 55% and the ratio of material to liquid at 1:15(g:mL).By using the optimized parameters, we obtained 0.639‰ extraction rate for CPT and 0.437‰ for HCPT.The extraction yields of CPT and HCPT extracted by homogenating technology were higher than those by other extractive methods, such as ultrasonic, reflux, shaking in water bath.It is concluded that the homogenate extraction technology was an efficient method for extracting CPT and HCPT from C.acuminata leaves, with characteristics of less extraction time and high yield.
文摘Objective: To evaluate the therapeutic as well as side effects of hydroxycamptothecin (HCPT) plus FOLFOX4 regimen as salvage therapy for patients with advanced gastric cancer. Methods: A total of 19 patients with advanced gastric cancer received HCPT plus FOLFOX4 as salvage therapy, in detail, Oxaliplatin 85 mg/m2 was given intravenously on day 1, CF 200 mg/m2, 5-Fu 400 mg/m2 given in bolus immediately after CF, days 1-2; 5-Fu 600 mg/m2 given continuously after bolus for 22 h on day 1, day 2, HCPT given intravenously at dosage of 10 mg/m2 on days 1-2. Therapeutic effects were evaluated at least after two cycles of treatment. Results: 17 cases among the 19 patients were valid for response evaluation, with CR 1 , PR 6, SD 4, PD 6. The response rate was 41.2%. For the 12 patients with liver metastasis, response rate of the liver foci was 50%. The main toxicities were bone marrow suppression, nausea and vomiting, and peripheral neuropathy; there were no chemotherapy-related deaths. Conclusion: The combination regimen with HCPT plus FOFLOX4 regimen was effective as salvage therapy for patients with advanced gastric cancer, with particularly high response rate for liver metastasis, and the side effects were tolerable and manageable.
文摘Hydroxycamptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro. This is the first study to investigate the release, distribution, and efficacy of hydroxycamptothecin which was incorporated into the biodegradable polymer Polylactic Acid (PLA), and implant into brain directly. In vitro release curve generated showed that a large initial release occurred over the first three days and was followed by a steady, but considerably slower rate of release over the next 25 days. After implanting the discs into 40 male SD rats, the animals were followed up to 28 days, where the concentration in brain tissue was far higher than that in peripheral blood at the each of the eight time-points evaluated, and it was also within the therapeutic range for C6 cells tested in vitro. The in vivoefficacy of the discs was evaluated with rats inoculated intracranially with C6 glioma and treated with hydroxycamptothecin polymer compared to intravenous as well as intratumoral injections;the median survival is 21.1, 13.9, 14.9 days, respectively. Given these data, we conclude that the biodegradable polymer PLA releases hydroxycamptothecin, producing tumoricidal levels in brain tissues and prolonging survival in a rat glioma model.
文摘Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in the bladder are observed in some patients. There are numerous reports of trials of intravesical instillation of anticancer agents with the objective of lowering this recurrence rate. The aim of this study was to compare the prophylactic efficacy and safety of epirubicin （EPI）, pirarubicin （THP） and hydroxycamptothecin （HCPT） in superficial bladder cancer.Methods This study enrolled a total of 189 patients who had been diagnosed with superficial bladder cancer during the period from 2004 through 2007 at Beijing Friendship Hospital. All patients were randomly allocated to one of three treatment groups. Patients in group A received 29 doses of EPI 30 mg/30 ml, patients in group B received 29 doses of THP 30 mg/30 ml, and patients in group C received 29 doses of HCPT 30 mg/30 ml, over a period of 24 months.Results The recurrence-free rate in the 2 anthracycline treatment groups （A and B） were significantly better than that of the HCPT treatment group. In the safety evaluation, the incidences of pollakiuria, pain on urination, dysuria, hematuria,and contracted bladder were not significantly different between groups A and B, but some were significantly higher in groups A and B than that in group C.Conclusion The efficacy of EPI and THP was significantly better than HCPT in the prevention of bladder cancer recurrence.
