5-Fluorouracil(5-FU)has been widely used to treat gastrointestinal,head,neck,chest and ovarian malignant tu-mors since 1957. As an analogue of pyrimidine,5-FU plays anti-cancer roles by inhibiting thymioylate synthase and integrating its me-tabolites into DNA and RNA. Although 5-FU is one of the first-line therapeutic compounds for gastrointestinal malignant tumor as a sin-gle drug or in combination with other drugs,its effectiveness is hindered by its low efficiency,which may be due to chemotherapy re-sistance. 5-FU chemotherapy resistance may stem from enzyme abnormality,genetic abnormality and tumor microenvironment. In this paper,we make a review about 5-FU actions and the mechanisms underlying chemotherapy resistance.

Colorectal cancer(CRC)ranks the third in incidence and mortality rate among human tumors. Tumor relapse,me?tastasis and drug resistance remain the main obstacle to the success of CRC treatments. Compared to traditional chemotherapy ,target therapy seems to treat tumors in more precise and rational fashion with good response and often less toxic side-effect. Although target agents provide hope for more effective therapy,recent clinical studies have shown only modest benefit from target therapy similar to tra?ditional chemotherapy. Primary and secondary resistance to target agents is still observed and contributes to CRC treatment failure. The review summarizes research progress in the mechanism of drug resistance to target therapy in CRC treatment.

OBJECTIVE To investigate the effect of bevacizumab ,an anti-human vascular endothelial growth factor monoclonal antibody,on pulmonary dissemination of colorectal cancer. METHODS A metastatic colorectal cancer mouse model was established. Mice were randomly divided into two groups(n=8). The mice in experimental group were administered ip with bevacizumab at the dosage of 5 mg · kg-1,and those in control group were given isotype IgG at the same dosage. The antibodies were administered on 2 d before initiation of model establishment and 2 d after that,then once every 5 d for 4 weeks,for a total of 7 times. Liver and lung metastases were determined by histopathological examination. The chemokine receptor C-X-C receptor 4(CXCR4)and its ligand C-X-C ligand 12(CXCL12)mRNA expression in the lung were detected by quantitative RT-PCR. Human colon cancer cells HCT116 were treated with bevacizumab(5 mg·L-1)for 24 h. The expression levels of vascular endothelial growth factor receptor 1(VEGFR1)and CXCR4/7 protein as well as CXCR3/4/7 mRNA were examined by Western blotting and quantitative RT-PCR respectively. RESULTS The number of mice(2/8) with liver metastases was reduced,while the number of mice(8/8) with lung metastases increased in experimental group compared with isotype IgG-treated group(6/8 and 2/8 respectively,P<0.05). The mRNA expression level of CXCR4 and CXCL12 in lung tissue was significantly up-regulated in bevacizumab-treated group com?pared with control group(P<0.05). The mRNA and protein expression level of CXCR4 and CXCR7 was dramatically increased in HCT116 cells treated with bevacizumab(P<0.05). CONCLUSION Bevacizumab can potentially promote lung metastases of colorectal cancer,which may be related to up-regulation of CXCR4 and CXCL12 expression.

Complement system is an important component of innate immunity and has been recognized as an effective means to inhibit tumor. However,in last decades,accumulating studies showed unexpected results that the complement components and their activation products could promote development of malignancies by secreting growth factors,activating signal pathway and promoting tumor angiogenesis. Herein,the relationship between the complement system and tumor is reviewed.

ObjectiveTo assess the impact of intense pulsed light (IPL) on the dermatopathological manifestation in a Bama miniature pig model of steroid-induced dermatitis.MethodsFive female Bama miniature pigs aged two months were selected.The white skin areas with white hair at both sides of the neck served as the target area.Halometasone(0.05％) cream was applied to the right target area twice daily for 60 days to establish a model of steroid-induced dermatitis.Then,3 pigs were randomly selected and irradiated with IPL of 25 J/cm2 at the model area with an interval of 3 weeks for 9 weeks,the remaining 2 pigs receiving no treatment served as the natural recovery group.Finally,skin tissues were obtained from the left and right target areas and subjected to haematoxylin and eosin staining for the observation of histopathological changes.ResultsA significant increase was observed in the layer number of keratinocytes and thickness of dermal collagen fiber in the IPL-treated pigs compared with the pigs in natural recovery group (6.27 ± 1.26 vs.2.98 ±0.92,t =3.27,P＜ 0.01; 1.88 ± 0.19 mm vs.0.84 ± 0.15 mm,t =4.25,P＜ 0.01).Moreover,IPL irradiation resulted in the regression of telangiectasis in the dermis.ConclusionIPL may increase skin thickness,relieve flushing and improve skin elasticity efficiently.

Objective To investigate and compare the killing effect of photodynamic therapy (PDT)induced by hematoporphyrin derivative (HpD),hematoporphyrin monomethyl ether (HMME) and photocarcinorin (PsD007) on human leukemia cells K562 in vitro.Methods Human leukemia cells were cultured with serial concentrations of photosensitizers followed by irradiation of different dosage of laser light,then MTT colorimetric assay was applied to measure the relative survival rate of PDT for the cells.Results Significant difference in the inhibitory between the PDT group and control group was observed (P＜0.05).The survival rate of PDT for the cells elevated along with the increase in the concentration of sensitizer and dose of laser light.When the photosensitizer concentration was bigger (25 μg/ml) or the energy density was bigger (7.2 J/cm2),the effect of PsD007 was better than HMME,and they were significantly better than HpD (P＜0.05).Conclusion PDT has significant killing effect on human leukemia cells K562,and its relative inhibitory rate appears to be correlated with the dose of sensitizer and laser light irritation.The effect of PDT is related to the photosensitizers.The effect of HpD-PDT is not as effective as PsD007 and HMME.On the conditions of higher energy density and larger photosensitizer concentration,the effect of PsD007-PDT is better than HMME-PDT.

Objective To assess the in vitro antimite activity of artemether against Demodex folliculorum, and to provide evidence for the use of artemether in the treatment of skin diseases caused by Demodex folliculorum infection. Methods Artemether was diluted to different concentrations(20, 10, 5 and 2.5 g/L)with peanut oil. The pH values of working solutions of artemether and peanut oil were measured. Demodex folliculorum mites were divided into several groups(32 mites in each group)to be treated with artemether(20, 10, 5 and 2.5 g/L, artemether groups) or peanut oil(control group). Results There were significant differences in the time required for killing of Demodex folliculorum among the 20?, 10?, 5?and 2.5?g/L artemether groups and control group(Median[P25-P75]:3.00[2.00-3.88]vs. 6.00[4.13- 7.25]vs. 13.00[11.63- 14.50]vs. 17.00[15.25- 20.75]vs. 34.00[23.50- 39.50]hours, H=133.954, P<0.001). Additionally, the time required for killing of Demodex folliculorum was significantly shorter in these artemether groups than in the control group(all P<0.001), and was gradually shortened with the increase of artemether concentrations, but was similar between the 10? and 20?g/L artemether groups(P > 0.05). Moreover, the pH values of working solutions of artemether and peanut oil ranged between 7.0 and 7.1, and were close to neutral. Conclusion Artemether at 20, 10, 5 and 2.5 g/L can kill Demodex folliculorum in vitro, so artemether may serve as an alternative drug for the treatment of Demodex folliculorum infection.

Objective To evaluate the role of recombinant human soluble Tim-3 (hTim-3-Fc) in regulating immune response.Methods Soluble hTim-3 was incubated with human macrophage cell line U 937, human T cell line Jurkat and normal human PBMC before cytokines secreted by or expressed in different immune cells were analyzed using ELISA , RT-PCR and Western-blotting, respectively.Results Soluble hTim-3 significantly promoted the activation of different immune cells.Our data showed that IL-8 secretion by U937 cells, IL-2 secretion by Jurkat cells , IL-2 and IFN-γsecretion by human PBMCs were all significantly increased .In addition , soluble hTim-3 significantly increased the IFN-α2 and IFN-β1 mRNA expression in U937, Jurkat and PBMCs and increased the phosphorylation of stat-1 in Jurkat and U937 cells.Conclusion Recombinant soluble hTim-3 can significantly promote the activation of immune cells in vitro, which shows its therapeutic potential .

In this paper, polyethylene glycol (PEG) of different molecular weight was grafted on the polyethylene terephthalate (PET, Dacron) films by plasma surface grafting modification. The competitive adsorption relation of plasma (fibrinogen and albumin) adsorbing on materials surface was analyzed in light of surface energy and interface free energy. The results indicated that the PET films grafted PEG long chain molecular possesses the characteristic of preferentially adsorbing albumin and this adsorption tendency of grafted PEG6000 sample is most distinct. The platelet adhesion tests of the PET films whose surfaces were pre-set in contact with fibrinogen and albumin indicated that the surface adsorbing albumin can distinctly inhibit platelet adhesion and aggregation and possess favorable blood compatibility, but the surface adsorbing fibrinogen can enhance platelet adhesion and aggregation.
Adsorption ; Biocompatible Materials ; chemistry ; Humans ; Plasma ; Platelet Adhesiveness ; Polyethylene Glycols ; chemistry ; Polyethylene Terephthalates ; chemistry ; Serum Albumin ; Surface Properties

Objective To examine whether Tim-3 plays a protective role in paraquat poisoning induced excessive immune response and tissue damage based on the critical roles of Tim-3 controlling inflammatory response.Methods A paraquat poisoning model was established in wild type and in Tim-3 transgenic C57BL/6 mice by intraperitoneal injection of paraquat (40 mg/kg) .In addition, C57BL/6 mice with paraquat poisoning were injected with Tim-3 soluble protein( sTim-3) or control protein to see the effect of Tim-3 blocking on the progression of paraquat poisoning.Samples were collected at 6 and 24 h after paraquat injection respectively and were examined for tissue damage, cytokine expression and paraquat metabolism.Results After paraquat poisoning, there was significantly attenuated tissue damage in the lungs and kidneys and decreased TNF-α,IL-6 and IL-1 beta expression in the PBMCs or in the serum from Tim-3 transgenic mice compared to wild type mice.The serum concentration of paraquat in Tim-3 transgenic mice was also significantly decreased.However, in sTim-3 treated paraquat poisoning mice, there was significantly increased cytokine expression and tissue damage compared to control protein treated mice.The in vitro data showed that Tim-3 signaling negatively regulated macrophages mediated inflammatory response.Conclusion Tim-3 plays a critical role in maintaining the homeostasis after paraquat poisoning. Further investigation on the regulatory roles of Tim-3 in inflammation will shed new light on the pathogenesis of paraquat poisoning and provide new therapeutic strategies.