Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.

Bevacizumab plus infusional 5-fluorouracil,leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy:A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

Non-platinum-based chemotherapy for treatment of advanced gastric cancer:5-fluorouracil,taxanes,and irinotecan

Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.

Re-evaluation of antitumor effects of combination chemotherapy with interferon-α and 5-fluorouracil for advanced hepatocellular carcinoma

AIM： To evaluate the efficacy of combination chemotherapy with interferon-α （IFNα） and 5-fluorouracil （5-FU） in patients with advanced hepatocellular carcinoma （HCC）. METHODS： Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNα/ 5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNα （3×10^6 units） was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU （500 mg/d） was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4th wk. The effect of combination chemotherapy was evaluated in each patient alter every cycle based on the reduction of tumor volume. RESULTS： Alter the 1^st cycle of therapy, 16 patients showed a partial response （PR, 57.1%） but none showed a complete response （CR, 0%）. At the end of therapy, the number of patients who showed a CR, PR, or no response （NR） was 1, 10, and 17, respectively. The response rate for therapy （CR＋PR） was 21.5%. Biochemical tests before therapy were compared between responsive （CR＋PR） and non-responsive （NR） patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis. CONCLUSION： Attempts should be made to discriminate between responders and non-responders by evaluating tumor size alter the first cycle of IFNα/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored. 2005 The WJG Press and Elsevier Inc. All rights reserved

Safety and Efficacy of Neoadjuvant DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] Chemotherapy Regimen in Patients with Locally Advanced Gastric and Gastro-Esophageal Junction Cancers: A Single Center Experience from India

Background:?The role of chemotherapy in Gastric Cancer is constantly evolving?with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric cancer (LAGC) namely Platinum based compounds (Cisplatin, Oxaliplatin), Fluoropyrimidines like 5-Flurouracil [(5-FU), Capecitabine)], Taxanes (Docetaxel) and Anthracyclines (Epirubicin). Various doublet and triplet combination chemotherapy regimens have been used for neo-adjuvant chemotherapy (NACT) in LAGCs. In this study we evaluated the safety and efficacy of docetaxel based triplet regimen DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] in LAGC. Material and methods:?50 Newly diagnosed patients of Locally Advanced Gastric Cancer (stage II or III) deemed fit to receive chemotherapy were included in our study. After 3 cycles of neoadjuvant chemotherapy, patients were assessed based on radiological and pathological response.?Results: 50 Patients were included in our study of which majority were male (32), median age at presentation was 55 years and 24 patients presented with a history of gastrointestinal reflux disease (GERD). The most common hematological toxicities observed in our study were anemia (61.2%), neutropenia (42.6%, febrile neutropenia constituted 6%) and thrombocytopenia (13.2%). The most common gastro-intestinal [GI] toxicities observed in our study included nausea (69.2%), vomiting (31.2%), diarrhea (34%), oral mucositis (14%) and constipation (6.6%). We found that safety profile of DOF regimen was favorable with majority of patients tolerating the regimen well. The Overall Response Rate (68%), Disease Control Rate (96%) and Resectability Rate (80%) were higher compared to western studies. Pathological CR (17.5%), ypN0?disease status (42.5%) and nodal down staging (52%), all showed positive correlations with survival outcomes. Conclusion:?DOF regimen is an effective and feasible option for neoadjuvant treatment of LAGC in an Indian population.

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of microribonucleic acids

5-flurouracil(5-FU)-based chemotherapy is the main pharmacological therapy for advanced colorectal cancer(CRC).Despite significant progress in the treatment of CRC during the last decades,5-FU drug resistance remains the most important cause of failure in CRC therapy.Resistance to 5-FU is a complex and multistep process.Different mechanisms including microsatellite instability,increased expression level of key enzyme thymidylate synthase and its polymorphism,increased level of 5-FU-activating enzymes and mutation of TP53 are proposed as the main determinants of resistance to 5-FU in CRC cells.Recently,microribonucleic acids(miRNA)and their alterations were found to have a crucial role in 5-FU resistance.In this regard,the miRNA-mediated mechanisms of 5-FU drug resistance reside among the new fields of pharmacogenetics of CRC drug response that has not been completely discovered.Identification of the biological markers that are related to response to 5-FU-based chemotherapy is an emerging field of precision medicine.This approach will have an important role in defining those patients who are most likely to benefit from 5-FU-based chemotherapy in the future.Thereby,the identification of 5-FU drug resistance mechanisms is an essential step to predict and eventually overcome resistance.In the present comprehensive review,we will summarize the latest knowledge regarding the molecular determinants of response to 5-FU-based chemotherapy in CRC by emphasizing the role of miRNAs.

Positron emission tomography complete metabolic response as a favorable prog-nostic predictor in esophageal cancer following neoadjuvant chemotherapy with docetaxel/cis-platin/5-fluorouracil

BACKGROUND 18F-fluorodeoxyglucose-positron emission tomography(PET)/computed tomography is useful in diagnosing lymph node and distant metastases of esophageal cancer.However,its value for predicting survival is controversial.AIM To evaluate the value of PET complete metabolic response(CMR)as a prognostic predictor for esophageal cancer.METHODS Between June 2013 and December 2017,58 patients with squamous cell esophageal cancer who underwent neoadjuvant chemotherapy(NAC)in Oita University were enrolled in this retrospective cohort study.Tumors were clinically staged using fluorodeoxyglucose-PET/computed tomography before and after NAC.After NAC,maximal standardized uptake value≤2.5 was defined as PET-CMR,and maximal standardized uptake value>2.5 was defined as non-PET-CMR.We compared short-term outcomes between the PET-CMR group and non-PET-CMR group and evaluated prognostic factors by univariate and multivariate analyses.RESULTS The PET-CMR group included 22 patients,and the non-PET-CMR group included 36 patients.There were no significant differences in intraoperative and post operative complications between the two groups.Five-year relapse-free survival and overall survival in the PET-CMR group were significantly more favorable than those in the non-PET-CMR group(38.6 mo vs 20.8 mo,P=0.021;42.8 mo vs 25.1 mo,P=0.011,respectively).PET-CMR was a significant prognostic factor in terms of relapse-free survival by univariate analysis(hazard ratio:2.523;95%confidence interval:1.034–7.063;P<0.041).Particularly,PET-computed tomography negative N was an independent prognostic factor of relapse-free survival and overall survival by multivariate analysis.CONCLUSION PET-CMR after NAC is considered a favorable prognostic factor for esophageal cancer.Evaluation by PET-computed tomography could be useful in clinical decision making for esophageal cancer.

Clinical Study of Combining Chemotherapy of Oxaliplatin or 5-Fluorouracil/Leucovorin with Hydroxycamptothecine for Advanced Colorectal Cancer

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.

PREOPERATIVE CHEMOTHERAPY OF CONTINUOUS INFUSION OF 5-FLUOROURACIL, EPIRUBICIN OR PIRARUBICIN AND CYCLO- PHOSPHAMINE IN OPERABLE PRIMARY BREAST CANCER

Objective: To evaluate the feasibility and activity of continuous-infusion of fluorouracil in association with epirubicin or pirarubicin and cyclophosphamine as neoadjuvant regimen in patients with primary breast cancer. Methods: A total of 111 (including 114 breasts) were entered into the study. Chemotherapy consisted of two to six cycles of epirubicin 50 mg/(m2穌) and cyclophosphamide 500 mg/(m2穌) on day 1 and 8, and continuous intravenous administration of 5-fluorouracil 200 mg/(m2穌) from day 1 to 28 with a microinfusional elastomer (CEFci) or pirarubicin 35 mg/(m2穌) on day 1 and 8 instead of epirubicin (CTFci). Results: The overall response rate was 87.7%. Forty-five patients (39.5%) attained a complete clinical response and 27 (23.7%) attained a pathological complete response. CTFci regimen was superior to CEFci regimen in response rate,the pathological complete response rate (pCR) of former regimen was significantly higher than that of latter regimen (34.8% vs. 16.2%) (P=0.022). The pCR rate in ER/PgR negative tumor was significantly higher than that of ER/PgR positive tumor, achieving 33.3% and 7.5% respectively (P=0.001, x2=11.043). There was no relationship between HER-2 expression and tumor response. The toxicity of two regimens was well tolerated. Alopecia was mild in CTFci regimen comparing with CEFci regimen but neutropenia in CTFci regimen was higher than CEFci regimen. Conclusion: Continuous-infusion of fluorouracil in association with epirubicin or pirarubicin and cyclophosphamine is effective regimens as neoadjuvant chemotherapy for primary breast cancer and the toxicity is well tolerated. Pirarubicin regimen was superior to epirubicin regimen in response rate.

Application and Effect Evaluation of the Integrated“5A and 3+3”Management Model in the Safe Medication Use for Chemotherapy Patients

Objective:To explore the application and effect evaluation of the integrated“5A and 3+3”management model in ensuring safe medication use for chemotherapy patients.Methods:A total of 100 intravenous chemotherapy patients admitted to the oncology department of Shaanxi Provincial People’s Hospital were randomly divided into two groups using a random number list method.Both groups received conventional nursing management during chemotherapy,while the study group additionally received the integrated“5A and 3+3”safety management model.The nursing intervention effects between the two groups were compared.Results:After the intervention,the study group showed higher levels of self-management ability,compliance,and nursing satisfaction compared to the control group.The overall incidence of adverse events during hospitalization was lower in the study group,with statistically significant differences(P<0.05).The knowledge scores of medical staff in the study group,related to the prevention and treatment of chemotherapy drug side effects,daily symptom management,and daily life management,were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion:Implementing the integrated“5A and 3+3”model in the safe medication management of intravenous chemotherapy patients can effectively enhance patients’self-management abilities and compliance,improve medical staff’s ability to safely administer chemotherapy drugs,reduce adverse events caused by chemotherapy,and increase patient satisfaction.

Synthesis of Aminoglucose Conjugates of 5-Fluorouracil-1-acetic Acid and 5-Fluorouracil-1-propanoic Acid and Their Antitumor Activities

Six aminoglucose conjugates were synthesized by the reaction of aminoglucose with 5-fluorou-racil-1-acetic acid or 5-fluorouracil-1-propanoic acid and confirmed by IR, 1H NMR and elemental analyses. Their antitumor activities against A2780 cells and PC-14 cells were also evaluated.

亲肿瘤显像剂5-^(18)F-Fluorouracil(^(18)F-FU)的标记合成研究

用18 F F2 与Uracil的直接标记法合成了 5- 18F -Fluorouracil,探索18F -FU -PET显像对结肠直肠癌肝转移病人化疗前后疗效评价的意义。产品的放射化学纯 >95% ,放射性得率为 60 % ,pH值为 7,无菌性试验和热源试验均为阴性 ,这一结果为临床应用提供了保证。

Cooperative inhibitory effect of sinomenine combined with5-fluorouracil on esophageal carcinoma

AIM:To investigate the inhibitory effects of sinomenine(SIN)combined with 5-fluorouracil(5-FU)on esophageal carcinoma in vitro and in vivo.METHODS:Esophageal carcinoma(Eca-109)cells were cultured in DMEM.The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8dye in living cells.Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis.Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis.SIN at 25mg/kg and 5-FU at 12 mg/kg every 3 d,either combined or alone,was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.RESULTS:SIN and 5-FU,both in combination and individually,significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis.Furthermore,the combined effects were greater than those of the individual agents(P<0.05).Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control(P<0.05).The up-regulation of Bax and downregulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway.SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo,and the combined inhibition rate was even higher(P<0.05).During the course of chemotherapy,no obvious side effects were observed in the liver or kidneys.CONCLUSION:The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds,and the drug combination did not increase the side effects of chemotherapy.

Breast Cancer Resistance Protein Expression and 5-Fluorouracil Resistance

Objective To filtrate breast cancer resistance protein （BCRP）-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance. Methods MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography （HPLC） assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immunohistochemistry （IHC） were employed to investigate the BCRP expression in breast cancer tissue specimens. Results MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil （5-Fu） （P〈0.05, n=3） in the cell model, while HPLC assay indicated that the intracellular retention dose of 5-Fu was significantly correlated with the expression of BCRP （t=-0.897, P〈0.05, n=3）. A total of 140 breast cancer tissue specimens were collected. BCRP-positive expression was detected in forty-seven specimens by both RT-PCR and IHC. As shown by MTT assay subsequently, the resistance index （RI） of 47 BCRP-positive breast cancer tissue specimens to 5-Fu was 7-12 times as high as that of adjacent normal tissue samples. BCRP expression was related to 5-Fu resistance （R2=0.8124, P〈0.01）. Conclusion Resistance to 5-Fu can be mediated by BCRR Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.

Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin,cisplatin, and 5-fluorouracil regimen for advanced gastric cancer:A systematic review and meta-analysis

BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better.AIM To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis.METHODS Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival(PFS), overall survival(OS), objective response rate(ORR), disease control rate(DCR), and adverse effects(AEs) as endpoints for analysis.RESULTS Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS(95%CI: 0.58-1.46, P = 0.73), OS(95%CI: 0.65-1.10, P = 0.21),and total AEs(95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR(95%CI: 1.13-1.75, P = 0.002) and DCR(95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group(95%CI: 1.16-1.88, P = 0.002),especially for neutropenia and febrile neutropenia.CONCLUSION With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.

Twenty-four hour intra-arterial infusion of 5-fluorouracil,cisplatin,and leucovorin is more effective than 6-hour infusion for advanced hepatocellular carcinoma

AIM. To evaluate the time dependence of intra-arterial 5-fluorouracil （5-FU） therapy for advanced hepatocellular carcinoma （aHCC）. METHODS： Thirty-seven adult Japanese patients who had aHCC and liver cirrhosis were treated with combined intra-arterial 5-FU, cisplatin （CDDP）, and leucovorin （LV）. The Japan Integrated Staging score （JIS score） of each patient was 3 or more. The patients were divided into two groups, alter which the 15 patients in group S were treated with 6-h infusion chemotherapy （LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 4 h） and the 22 patients in group L were treated with 24-h infusion chemotherapy （LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m^2 per 22 h）. Continuous infusion chemotherapy was performed v/a the proper hepatic artery every 5 d for 4 wk using an implanted drug reservoir. RESULTS： The percentages of patients with a partial response after 4 wk of chemotherapy were 6.7% in group S and 31.8% in group L. The survival of group L was significantly better than that of group S, with the median survival time being 496 d in group L and 226 d in group S （P 〈 0.05）. CONCLUSION： Continuous 24-h intra-arterial infusion is more effective for aHCC and can markedly prolong survival time as compared to 6-h infusion.

Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice

AIM: To prepare chitosan-polyaspartic acid-5-fluorouracil (CTS-Pasp-5Fu) nanoparticles and investigate its anti-carcinoma effect and toxicity. METHODS: CTS-Pasp-5Fu nanoparticles were synthesized by ionic gelatification. Male BABL/c nude mice were injected with SGC-7901 gastric carcinoma cell line mass to establish a human gastric carcinoma model. They were randomly allocated into 4 groups: CTS-Pasp-5Fu (containing 5-Fu 1.25 mg/kg), 5-Fu (1.25 mg/kg), CTS-Pasp and normal saline groups. Tumor weight was measured and assay of colony forming unit-granulocyte and macrophage (CFU-GM) was performed. The structural change of cells and tissues was observed and the Bax and Bcl-2 genes were detected. RESULTS: Compared with normal saline, the inhibition rates of tumor growth for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.58%, 58.69% and 70.82%, respectively. The tumor inhibition rates for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.09%, 65.3% and 72.79%, respectively. There was a significant decrease in the number of CFU-GMformation and increase of total bilirubin, and alanine aminotransferase in the 5-Fu group, but no change in those of the other three groups. There was no change in white blood cell count and creatinine among the four groups. Pathological section of liver and nephridial tissues showed that the damage in the 5-Fu group was more severe than that in the CTS-Pasp-5Fu group. 5-Fu and CTS-Pasp-5Fu groups could both down-regulate the Bcl-2 expression and up-regulate the Bax expression to different extent, and the accommodate effect of CTS-Pasp-5Fu was more obvious than 5-Fu. CONCLUSION: The tumor inhibition rate of CTS-Pasp-5Fu nanoparticles is much higher than that of 5-Fu alone.

Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposomes in vivo and in vitro

AIM:To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry. RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100 μmol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 μmol/L) was lower than that of free 5-Fu (51.2 μmol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears to have anti-hepatocarcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.

Thymidylate synthase and thymidine phosphorylase gene expression as predictive parameters for the efficacy of 5-fluorouraci-based adjuvant chemotherapy for gastric cancer

AIM： To investigate the prognostic role of thymidylate synthase （TS） and thymidine phosphorylase （TP） mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS： Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouraci-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by realtime quantitative PCR.RESULTS： The median disease-free survival （DFS） time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS （14.4 mo vs 8.3 mo, P = 0.017）. The median overall survival （OS） time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP （for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 too, P = 0.009）. Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene.CONCLUSION： Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy.