褪黑素通过调控EZH2表达增强食管癌细胞对5⁃氟尿嘧啶的敏感性

目的探讨褪黑素(melatonin,MLT)协同5⁃氟尿嘧啶(5⁃fluorouracil,5⁃FU)抑制食管癌细胞的作用及其分子机制。方法采用不同浓度的褪黑素和5⁃FU处理人食管癌EC⁃9706和EC⁃109细胞;通过检测细胞活性、侵袭迁移、细胞凋亡和蛋白表达来探讨褪黑素对5⁃FU化疗敏感性的影响,进一步探索其可能的作用机制。通过荷瘤实验探讨褪黑素和5⁃FU协同抗肿瘤的作用。结果褪黑素对EC⁃9706和EC⁃109细胞活力的抑制呈剂量依赖性;与空白对照组相比,褪黑素能够降低EC⁃9706和EC⁃109细胞的侵袭和迁移能力(P<0.01),增加细胞的凋亡率(P<0.01)。与单独褪黑素和5⁃FU药物处理组比较,褪黑素和5⁃FU联合组显著降低食管癌细胞的增殖、侵袭和迁移,增加细胞凋亡(P<0.01)。同时,与单独褪黑素和5⁃FU药物处理组比较,褪黑素和5⁃FU联合组显著降低EZH2的表达。过表达EZH2能够逆转褪黑素和5⁃FU对EC⁃9706细胞的影响(P<0.01)。此外,与单独5⁃FU给药组比较,褪黑素和5⁃FU联合给药显著抑制裸鼠体内肿瘤的生长(P<0.01)。结论褪黑素和5⁃FU协同抑制EZH2的表达、促进食管癌细胞凋亡,提高5⁃FU对食管癌细胞的敏感性、抑制肿瘤生长。

大蒜素联合5⁃氟尿嘧啶对黏液表皮样癌MEC⁃1细胞增殖与凋亡的作用及机制

目的探讨大蒜素联合5⁃氟尿嘧啶(5⁃fluorouracil,5⁃FU)对黏液表皮样癌MEC⁃1细胞增殖抑制和凋亡的作用及机制,为临床药物应用提供相应基础。方法取对数生长期的MEC⁃1细胞,随机分成对照组和实验组,对照组为含有0.1%DMSO的PBS组,实验组为大蒜素组、5⁃FU组、联合用药组(大蒜素联合5⁃FU组)。用CCK8法检测不同浓度(0、25、50、75 mg/L)大蒜素、5⁃FU及大蒜素联合5⁃FU作用于MEC⁃1细胞24 h后细胞增殖抑制率并计算作用24 h后大蒜素及5⁃FU IC50值。用流式细胞仪检测不同浓度(0、25、50、75 mg/L)大蒜素、5⁃FU及大蒜素联合5⁃FU作用于MEC⁃1细胞24 h后细胞凋亡率。使用Western blot检测IC50浓度的大蒜素、5⁃FU单独及联合作用于MEC⁃1细胞24 h后Bax、Bcl⁃2蛋白表达量。结果联合用药组对MEC⁃1的增殖抑制率及凋亡率均强于大蒜素组和5⁃FU单独用药组(P<0.01)。大蒜素与5⁃FU单独及联合使用均可以下调Bcl⁃2蛋白和上调Bax蛋白表达量,且联合用药组Bax/Bcl⁃2比值最大(P<0.05)。结论大蒜素和5⁃FU单独及联合使用均对MEC⁃1细胞具有增殖抑制作用和诱导凋亡作用,且大蒜素增强了5⁃FU对MEC⁃1细胞的凋亡作用,其诱导MEC⁃1凋亡机制可能与Bax/Bcl⁃2信号通路相关。

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.

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.

Synthesis and stability evaluation of 5-FU-acetic podophyllic ester as anti-tumor agent

Aim To study a new anti-cancer drug 5-FU-acetic podophyllic ester derivatized from podophyllotoxin. Methods A novel derivative of podophyllotoxin was synthesized. Its inhibitory effects against P-388, A-549, Bel-7402 and HL-60 in vitro were tested. The stability tests under different kinds of conditions were carried out. Results The novel derivative showed stronger inhibitory activities against P-388, A-549 and Bel-7402 in vitro than VP-16. The novel derivative was found to be stable at 60 ℃ and 4500 1x light in solid-state, but was less stable in humid condition. It was more stable in methanol （4 ℃ ） and chloroform （25 ℃ ） than in methanol （25 ℃）, and less stable in artificial gastric juice （ AGJ, 37 ℃ ）. Its stabilities were decreased while increasing the pH of buffer solutions. Conclusion These results could provide useful information for further study of this compound.

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.

5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors

In order to improve the cancer-targeting and selective activity of antineoplastic agent [5-fluorouracil （5-FU）], a novel pH-responsive drug delivery system [pullulan acetate/sulfonamide （PA/SDM） conjugate] was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobicaUy modified pullulan acetate to enhance the pH sensitivity for better cancer-targeting delivery. 5-FU was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameter of the self-assembled particles was approximately 100nm, with uniform size and good spherical morphology. The nanoparticles showed good stability at pH 7.4, which is equal to that of the normal body fluid, but shrank and aggregated below pH 6.8, which is close to the pH with tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UVNis spectrophotometer. The release profile was heavily pH-dependent around phvsiological pH, and the release rate was significantly enhanced under pH of 6.8.

CpG oligodeoxynucleotides inhibit tumor growth and reverse the immunosuppression caused by the therapy with 5-fIuorouracil in murine hepatoma

AIM: To investigate the effect of CpG-containing oligodeoxynucleotides (CpG ODN) alone or in combination with the chemotherapeutic agent 5-fluorouracil (5-FU) on tumor growth and whether CpG ODN can reverse the immunosuppression caused by the chemotherapy with 5-FU in murine hepatoma model. METHODS: Hepatoma model was established by subcutaneous inoculation with hepatoma-22 (H22) cells into the right flank of BALB/c mice. Mice with tumor were treated by peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU. Tumor size was quantified regularly. Serum levels of IL-12 and IFN-γ in mice were assayed by enzyme-linked immunosorbent assay (ELISA). The lytic capacity of splenic NK cells was tested by lactate dehydrogenase release assay. RESULTS: Peritumoral injection of CpG ODN alone or in combination with subcutaneous injection of 5-FU, and the treatment with 5-FU alone all led to significant inhibition of hepatoma growth. The mean tumor volumes fell by 46.66% in mice injected with CpG ODN, 68.34% in the 5-FU treated mice, and 70.23% in mice treated with the combination of CpG ODN and 5-FU than in controls. There was no significant difference in tumor size between 5-FU-treated mice and mice treated with the combination of 5-FU and CpG ODN (P>0.05). The serum levels of IL-12 and IFN-γ of mice treated with CpG ODN alone (IL-12: 464.50±24.37 pg/mL; IFN-γ: 134.20?5.76 pg/mL) or with the co-administration of CpG ODN and 5-FU (IL-12: 335.83±28.74 pg/mL; IFN-γ: 111.00±5.33 pg/mL) were significantly higher than that of controls (IL-12: 237.50±45.31 pg/mL; IFN-γ: 56.75±8.22 pg/mL). The production of IL-12 and IFN-γ was suppressed moderately in 5-FU-treated mice (IL-12: 166.67±53.22 pg/mL; 53.33±16.98 pg/mL) compared to control mice (P>0.05), whereas the combination of CpG ODN and 5-FU significantly increased the serum levels of IL-12 and IFN-γ compared to 5-FU alone (P<0.05). The NK cell killing activity in CpG ODN-treated mice (44.04±1.38%) or the mice treated with CpG ODN combined with 5-FU (30.67±1.28%) was significantly potentiated compared to controls (19.22±0.95%, P<0.05). The co-administration of CpG ODN and 5-FU also significantly enhanced the lytic activity of NK cells when compared with the treatment with 5-FU alone (12.03±1.42%, P<0.05). CONCLUSION: The present data suggests that CpG ODN used as single therapeutic agent triggers anti-tumor immune response to inhibit the growth of implanted hepatoma and reverses the immunosuppression caused by the chemotherapy with 5-FU.

5-Fluorouracil concentration in blood, liver and tumor tissues and apoptosis of tumor cells after preoperative oral 5'-deoxy-5-fluorouridine in patients with hepatocellular carcinoma

AIM: To study the levels of 5-fluorouracail (5-FU) in plasma, liver and tumor in patients with hepatoceilular carcinoma after oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR). METHODS: Thirty-nine patients with hepatoceilular carcinoma were treated with oral 5'-DFUR for more than 4 d before operation. The contents of 5-FU in plasma, liver and tumor were measured by high performance liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in-situ TUNEL after resection of tumor. RESULTS: The concentrations of 5-FU were 1.1 μg/mL, 5.6, 5.9, and 10.5 μg/g in plasma, the liver tissue, the center of tumor and the periphery of tumor, respectively. 5-FU concentration was significantly higher in the periphery of tumor than that in the liver tissue and the center of tumor (10.5±1.6 μg/g vs 5.6±0.8 μg/g, t = 21.38, P<0.05; 10.5±1.6 μg/g vs 5.9±0.9 μg/g, t = 20.07, P<0.05). 5-FU level was significantly lower in plasma than that in the liver and the tumor (1.1±0.3 μg/mL vs 5.6±0.8 μg/g, t = 19.63, P<0.05; 1.1±0.3 μg/mL vs 10.5±1.6 μg/g, t= 41.01, P<0.05). Apoptosis of tumor cells was significantly increased after oral 5'-DFUR compared to the control group without 5-DFUR treatment. CONCLUSION: There is a higher concentration of 5-FU distributed in the tumor compared with liver tissue and apoptosis of tumor cells is increased following oral 5'-DFUR compared with the control group. The results indicate that 5'-DFUR is hopeful as neo-adjuvant chemotherapy to prevent recurrence after resection of hepatoceilular carcinoma.

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

Activity and safety of pegylated liposomal doxorubicin,5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma:A phase Ⅱ study

AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.

Successful treatment of advanced hepatocellular carcinoma by combined administration of 5-fluorouracil and pegylated interferon-a

We report a case of hepatocellular carcinoma （HCC） treated successfully by transarterial chemoembolization （TACE） followed by combination therapy of 5-fluorouracil （5-FU） and pegylated interferon-α （PEG-IFN-α）. In the present case, the patient had massive and advanced HCC with a diameter of over 8 cm located in segment 7 （S7） of the liver. Furthermore, the tumor invaded into the major branch of the portal vein （Vp3）. After TACE, combined administration of 5-FU and PEG-IFN-α was performed for 5 too. HCC was totally eradicated and the serum levels of tumor markers were markedly decreased by the treatment. Although it has been reported that the combined use of conventional IFN-α and 5-FU showed striking effects on HCC in some cases, this case may suggest the more promising effect of PEG-IFN-α with a long-lasting effect, in the combined use with 5-FU for the treatment of massive advanced HCC.

5-Fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-adenovirus receptor independent and associated with morphological changes in lipid membranes

AIM： To evaluate the mechanism underlying the effects of 5-Fluorouracil （5-FU） on adenoviral infection. METHODS： Low and high Coxsackievirus-Adenovirus Receptor （CAR） expressing human colon carcinoma cell lines were treated with 5-FU and two El-deleted adenoviral constructs, one transferring GFP （Ad/CMV- GFP） the other bax （Ad/CEA-bax）. The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU. RESULTS： Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU- treated liposomes appeared irregular and porous-like. CONCLUSION： adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy.

Treatment of Advanced Gastric Carcinoma Patients with Calcium Folinate,a 5-Fluorouracil Bolus and Continous Infusion with 5-Fluorouracil Combined with Oxaliplatin

OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advanced gastric carcinoma patients. METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin.The effects of treatment and toxicity were observed. RESULTS There were 4 complete responses,26 partial responses, 30 with no change and 5 with progressive disease.The overall effective response rate was 46.2%(30/65).The median duration was 7 months,with the main side effects including nausea and vomiting,peripheral phlebitis,alopecia,leukopenia,dental ulcers, peripheral neuritis and diarrhea.All the side effects were tolerated and minimal. CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma.This therapeutic regimen is of value for these patients.

Studies on In Vitro Slow-Release Characteristics and Anticancer Effect of 5-Fluorouracil-Loaded Immuno-Nanoparticles

OBJECTIVE To investigate slow-release features of biodegradable anticancer 5-fluorouracil-loaded immunonanoparticles （5-FU INPs）, and to assess their tumor cell killing activity in vitro.METHODS The method of vibrating dialysis at a constant temperature, and first-order derivative ultraviolet spectrophotometry were used to determine the drug-releasing character of 5-FU INPs. The methyl thiazolyl tetrazolium （MTT） colorimetric method was employed to assay the killing activity of 5-FU INPs on 5 tumor cell lines at different phases.RESULTS The 5-FU INPs had a favorable slow-release function, with a tl/2 release time of 10.4 days. The 5-FU INPs had a rather strong lethal effect on 5 tumor cell lines resulting in a positive correlativity between the killing activity and the action time and amount of the drug released.CON＇CLUSION The drug disposition is uniform from the 5-FU INPs, and there is no impact on efficacy of the 5-FU during preparation and degradation of the 5-FU INPs. The 5-FU INPs have a favorable function for drug release, and can maintain an effective killing activity over a long period of time.

Influences of Organic Solvents on Particle Size and Drug-loading Efficiency for 5-Fluorouracil Poly(lactic acid)Nanoparticles

The objective of this study was to investigate the influences of organic solvents on particle size, drug content, loading efficiency and yield for 5 Fluorouracil Poly(lactic acid) nanoparticles . The 5 Fluorouracil was entrapped into poly(lactic acid)(PLA) nanoparticles using a water in oil in water solvent evaporation technique. During the preparation process, ethyl acetate and acetone were used as organic solvents since they are less toxic than the more commonly used dichloromethane. The effect of the three solvents on particle size, drug content, loading efficiency and yield of nanopartcles was compared. When the solvent of the oil phase was acetone, the highest drug content, smallest particle size and lowest yield were obtained for the PLA nanoparticles.

NEUTROPHIL INFILTRATION IS INVOLVED IN 5-FLUOROURACIL INDUCED LIPID PEROXIDATIVE DAMAGE OF THE SMALL INTESTINE

This study evaluated the mechanisms of 5-fluorouracil (5-FU) induced intestinal damage by investi-gating the lipid peroxide (LPO) level, myeloperoxidase (MPO) activity and disaccharidase activity in rats.Group Ⅰ animals (n=6) were sacrificed and served as a normal control group. Group Ⅱ animaIes (n= 24 )were given a single intraperitoneal injection of 5-FU (150 mg/kg) and every 8 rats were sacrificed on day1,3 and 5 after injection respectively. Results: LPO concentration in blood and intestinal mucosa was sig-nificantly higher in the group Ⅱ than in the group Ⅰ on day 1 and 3 (P<0. 05) MPO activity was signif-icantly higher in the group I than in the group Ⅰ at different times (P<0. 01 ). Lactase activity on day 5(P<0. 01); sucrase activity (P<0. 01 and P<0. 05 respectiviely) and maltase activity (P<0. 01 ) on day3 and 5, were significantly lower in the group than in the group l. Conclusion: The results indicatethat neutrophil infiltration may be involved in 5-FU-induced lipid peroxidative damage of the small intes-tine which was reflected by the decreased disaccharidases activities.

Layered Double Hydroxide Modified by PEGylated Hyaluronic Acid as a Hybrid Nanocarrier for Targeted Drug Delivery

In recent years, organic-inorganic hybrid nanocarriers are explored for effective drug delivery and preferable disease treatments. In this study, using 5-fluorouracil(5-FU)as electronegative model drug, a new type of organic-inorganic hybrid drug delivery system(LDH/HA-PEG/5-FU)was conceived and manufactured by the adsorption of PEGylated hyaluronic acid(HA-PEG)on the surface of layered double hydroxide(LDH, prepared via hydrothermal method)and the intercalation of 5-FU in the interlamination of LDH via ion exchange strategy. The drug loading amount of LDH/HA-PEG/5-FU achieved as high as 34.2%. LDH, LDH/5-FU and LDH/HA-PEG/5-FU were characterized by FT-IR, XRD, TGA, laser particle size analyzer and SEM. With the benefit of p Hdegradable feature of LDH and enzyme-degradable feature of HA, LDH/HA-PEG/5-FU showed p H-degradable and enzyme-degradable capacity in in vitro drug release. Moreover, the drug carrier LDH/HA-PEG contained biocompatible PEG and tumor-targeted HA, resulting in lower cytotoxicity and better endocytosis compared with LDH in vitro. It was suggested that the organic-inorganic hybrid drug delivery system, which was endowed with the properties of controlled release, low toxicity and tumor-targeting delivery for ameliorative cancer therapy, was advisable and might be applied further to fulfill other treatments.

Anticancer effects of Xi Huang Capsule on breast cancer in vivo

Objective:To investigate the anticancer effects of Xi Huang Capsule(XH)in vivo,thirty-two Nu/Nu mice inoculated with human breast cancer SKBR-3 cells and twenty-four Nu/Nu mice inoculated with murine breast cancer 4T1 cells were randomized into the control group,XH group,5-FU group and combination of XH and 5-FU group in a 1:1:1:1 ratio.Method:The 5-FU group was injected with 5-FU at 30 mg/kg intraperitoneally every third day;XH group received doses of 0.25g/kg of XH by gastric perfusion each day;The control group was injected daily with normal saline(N.S.)intraperitoneally and the combination group was treated with 5-FU and XH on the same schedules as above.All treatments lasted for 15 days in human SKBR-3 breast cancer cells and 11 days in mice breast cancer 4T1 cells.Tumor volume,tumor weight,organ index,and change in body weight of nude mice were measured,respectively.PCNA and vimentin protein expression were examined by immunohistochemical assay.Results:In SKBR-3 cell xenograft tumor experiments,the XH group,5-FU group and the combination group had significantly smaller tumor volumes(966.39±80.23mm3,892.21±150.77mm3,817.93±162.47 mm3,respectively),and lower tumor weights(0.90±0.14g,0.84±0.32,0.86±0.24g,respectively),as compared with the control group(all P<0.05).The combination group had the highest tumor inhibition rate(38.7%).The similar results emerged in 4T1 cell xenograft tumor.Only the combination group had the least body weight increase of SKBR-3 cells xenograft tumor(P<0.05 as compared with the control group).In SKBR-3 cell xenograft tumor experiments,the 5-FU group had a lower Liver index(43.02±5.00mg/g versus 50.95±4.59mg/g)as compared with the control group(P<0.05),whereas the combination group reversed the changes in the 5-FU group with Liver index of 49.69±4.81 mg/g(P<0.05).The combination group had a higher Spleen index(5.95±1.62 versus 4.72±0.66mg/g)as compared with the control group,and had a higher Spleen index as compared with the 5-FU group(4.54±0.79 mg/g,P<0.05).In 4T1 cell xenograft tumor experiments,the 5-FU group and the combination group had a lower Liver index(47.69±6.41,49.87±5.96 versus 58.95±7.33),but Liver index of XH group had no significantly difference as compared with the control group.The Spleen index was the same to that in SKBR-3 cells xenograft tumor.PCNA and vimentin expression of XH group was significantly lower than that of the control group.Conclusion:The treatment of XH was equally effective in the inhibition of tumor growth,and may have potentially additional benefit in improving the general condition and immunity of the mice not only in human breast cancer cell but also in rat mammary carcinoma in vivo.

Spindle cell carcinoma of the breast as complex cystic lesion: a case report

Spindle cell carcinoma of the breast is a rare tumor. This tumor can proliferate rapidly and cause cystic changes because of internal tissue necrosis. We evaluated a 54-year-old woman with right breast lump. Mammography showed a category four mass with a diameter of 2.5 cm. Ultrasonography(US) revealed a complex cystic lesion, and fine-needle aspiration(FNA) cytology demonstrated bloody fluid and malignant cells. Partial breast resection and sentinel lymph node biopsy were performed. Immunohistology revealed spindle cells with positive results for cytokeratin(AE1/AE3) and vimentin, partially positive results for s-100, and negative results for desmin and α-actin. The pathological stage was IIA, and biochemical characterization showed that the tumor was triple negative. Six courses of FEC-100 chemotherapy(5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) were administered. Radiotherapy was performed. This case is discussed with reference to the literature.