ObjectiveTo investigate the effect of expressions of nucleoside transporters subtype (hENT1 and hENT2) on 5-fluorouracil(5-FU) cytotoxicity in breast cancer cell lines(MDA-MB-231, MDA-MB-468, SK-BR-3, MCF-7). MethodsFour breast cancer cell lines were chosen to detect the mRNA expressions of hENT1 and hENT2 by RT-PCR. Cells were incubated in the medium with a serial concentrations of 5-FU from 1.28×104 ng/L to 2.00×108 ng/L for 48 h. Then the cell proliferation in each cell line was measured by MTT assay and the IC50 was evaluated. Results①The mRNA expressions of hENT1 and hENT2 in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells were significantly higher than thoes in the MCF-7 cells(P < 0.05). The mRNA expression of hENT2 was detected in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells, not detected in the MCF-7 cells. 2MTT showed that IC50 of 5-FU in the MDAMB-231, MDA-MB-468, or SK-BR-3 cells was significantly lower than that in the MCF-7 cells(P < 0.05). There was no statistical difference of IC50 among the three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3)(P > 0.05).③The three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3) with lower IC50 of 5-FU highly expressed hENTs, and MCF-7 cell with the higher IC50 of 5-FU expressed less hENTs. ConclusionsThe expressions of hENTs in breast cancer cell lines can significantly influence 5-FU cytotoxic effect. It is implicated that the hENTs expressions might be the clue to the choice of nucleoside anticancer drugs in clinic.
Objective To investigate the effects of celecoxib-poly lactide-co-glycolide microparticles (CEL-PLGA-MS) on rat retina after intravitreal injection. Methods A total of 32 male Brown Norway rats were randomly divided into CEL-PLGA-MS group and celecoxib group, 16 rats in each group. The rats in CEL-PLGA-MS group were divided into four dosage group, four rats in each group, which received intravitreal injection of PLGA with celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. The rats in celecoxib group were divided into four dosage group, four rats in each group, which received intravitreal injection of celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. Phosphate buffer solution (PBS) was injected in two rats as PBS control group. Two rats as normal control group received no treatment. The difference of retinal thickness among groups was measured by optical coherence tomography (OCT). The morphological and histological change of retina was evaluated under light microscope and transmission electron microscope. Results There was no difference of retinal thickness between normal control group and PBS control group (F=0.12,P＞0.05). At the first week after injection, the retinal thickness of CEL-PLGA-MS group and celecoxib group were thicker than that in normal control group and PBS control group (F=9.62, 46.13;P＜0.01). The retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=165.15,P＜0.01). The retinal thickness was estimated equal among 40, 80, 320 mu;mol/L dosage groups in CEL-PLGA-MS group (F=4.79,P＜0.01). The retinal thickness of 160, 320 mu;mol/L dosage group were thicker than that in 40, 80 mu;mol/L dosage group in celecoxib group (F=28.10,P＜0.01). At the second week after injection, there was no difference of retinal thickness between CEL-PLGA-MS and celecoxib group (F=3.79,P＞0.05); the retinal thickness of CEL-PLGA-MS and celecoxib group became thinner gradually compare to the first week after injection (F=7.28, 103.99; P＜0.01). At the fourth week after injection, the retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=19.11,P＜0.01). The retinal thickness of CEL-PLGA-MS group was approximately the same to normal control group and PBS control group (F=2.02,P＞0.05). The retinal thickness of celecoxib group was thicker than that in normal control group and PBS control group. No considerable abnormality of the retina was seen by light microscope and the retinal thickness corresponded with the values measured by OCT at the first week after injection. The abnormal structures of the retina were seen in 160, 320 mu;mol/L dosage group of celecoxib group and inner changed evidently by the transmission electron microscope. Disordered arrangement of microfilaments, dilated microtubule and some mitochondria vacuolation were observed in 320mu;mol/L dosage group of celecoxib group. Others changed slightly. Conclusions CEL-PLGA-MS has less toxicity on the retina than free-celecoxib after intravitreal injection. The safety of intravitreal injection with CEL-PLGA-MS is better than celecoxib.
Objective To inverstingate the effect of perfluorohexyloctane(F6H8)to the retina of rabbit eyes. Methods Fifteen vitrectomized New Zealand white rabbits were injectedF6H8(experiment group,12 rabbits ) and BSS(control group,3 rabbits) into vitreous cavity.Slit-lamp biomicroscopy and indirect ophthalmoscopy were performed pre- and postoperatively in all the eyes.Histopathological examination was done after the rabbits were sacrificed at the end of the study. Results A large clear balb was formed after intravitreal injection of theF6H8 in the vitreous was injected and no retinal detachment and cataract were found.The OPL was edematous and then thinned out in 4th week in experimental group.Degenerating cells was found in inner and outer nuclear layers.Cellular vaculoar degeneration was present in TEM. ConclusionF6H8 in vitreous cavity may cause significant side effects on retina,we could not recommend it to be used as an intraocular temponade.
Purpose To investigate the protective effect ofldquo;haw drink compoundrdquo;against carbon disulfide (CS2)toxic retinal damage． Methods Thirty healthy white adult New Zealand rabbits were divided at random into 3 groups:the normal control group,the exposure control group and the treatment group．The experimental rabbits were contaminated by inhaling CS2 for 3 continuoues hours in 6 consecutive days in a week for totaly 3 weeks．The rabbits in the treatment group were given haw drink compound before containation．After 3 weeks of the experiment,the retinal tissues of the rabbits were examined with light microscope and transmissing electronmicroscope(TEM). Results The ultrastructures of the retinal tissues of the exposure control group were more abnormal than those of the treatment group and the normal control group．TEM showed that every layer cell of the retinal in the exposure control group showed apparent degenerative changes ,but that in the treatment group showed apparent degenerative changes,but that in the treatment group was nomal．The light microscpic picture showed that the inner segments and the outer segments of photoreceptors construction were destroyed,the nerve fiber layer was loose and ganglion celles vacuolated in the retinat of the exposure control group．TEM showed that The photorecepter synapses were vacuolated,the postsynaptic space became wider and the synaptic sticks disappered． Conclusion How drink compound can improve the tolerance to CS2 toxicity in inducing the retinal damage of rabbits. (Chin J Ocul Fundus Dis, 1999, 15: )
Objective To evaluate the toxic effects of staphylococcus aureus exotoxins and neutrophils on retinal pigment epithelium (RPE) cells (RPEC). Methods An in-vitro model of bacteroidal endophthalmitis was established by co-culturing of human RPE cell line D407 and human peripheral blood neutrophils in the present of staphylococcus aureus exotoxins ATCC29213. The level of lactate dehydrogenase hydroxide（LDH）in the cuture supernant was measured, and the viability of RPE was evlauated by flow cytometry and Hoechst 33342/Propidium Iodide（PI）staining. Results When RPE cells were cultured with the exotoxin ATCC29213, the LDH level and necrotic RPE cells were positive proportional to the dosage of exotoxin, but only 250mu;l or 500mu;l of ATCC29213 had a statistical significant effect. When RPE cells were co-cultured with neutrophils in the present of ATCC29213 for 6 hours, 100mu;l of ATCC29213 already had a statistical significant effect on LDH level and necrotic RPEC, and the effect was proportional to the amount of neutrophils in the culture. Conclusion Both staphylococcus aureus exotoxins and neutrophils can damage the RPEC by inducing necrosis, and their function had synergetic effect.
This study evaluated the cytotoxicity of a new type silicone rubber for maxillofacial prosthesis, which was developed by the present authors. According to the GB/T16886.5-2003, the samples were prepared and tested with cell counting kit-8 (CCK-8) assay, the relative growth rate (RGR) was calculated, and morphology of L929 cells were observed by scanning electron microscope and phase contrast microscope. The results showed that RGR of L929 cells were 91.65% (24 h), 87.03% (48 h), 87.30% (72 h), respectively, and the level of cytotoxicity was grade 1. The L929 cells showed typical fusiform shape and their morphology did not changed significantly after 24 h, 48 h and 72 h. These data indicated that the newly-developed silicone rubber material, as a maxillofacial prosthesis material, should be a safe biomaterial.
Fluoropyrimidines have been the standard care as ajuvant or palliative treatment for malignant gastrointestinal carcinoma over several decades. Their common adverse effects include gastrointestinal effects, myelosuppression, and hand-foot syndrome. Besides, fluoropyrimidines are the second cause of chemotherapy-induced cardiotoxicity and have the different manifestation and machanisms from anthracyclines. With the development of onco-cardiology, increasing concern is raised on fluoropyrimidine-induced cardiotoxicity. This review addresses the epidemiology, clinical manifestation, and proposed mechanisms; and also highlights the diagnosis, monitoring and management of fluoropyrimidine-induced cardiotoxicity.
Objective To evaluate the cytotoxicity of microdosis peracetic acid (PAA) so as to provide the evidence for making residual l imit of PAA steril ization. Methods Mouse fibroblasts (L929 cell l ine) cultured in vitro were observed to evaluate the influence of microdosis PAA including 1 × 10-6, 2 × 10-6, 3 × 10-6, 4 × 10-6, 5 × 10-6, and 10 × 10-6 (V/V). Theproliferation of cells was determined by MTT assay at 2, 4, and 7 days of culture. The growth curve and the relative growth rate (RGR) were obtained. The cytotoxicity of PAA at different concentrations was evaluated according to RGR. Results At 2, 4, and 7 days after culture, fibroblasts of 1 × 10-6 group grew with normal morphology analogous to control group, while the cell growth of other groups were poor. With the increase of PAA concentration, the absorbance (A) values decreased, which suggested that there was a significant negative correlation between cell prol iferation and PAA concentration. And the correlation coefficient was — 1.000 at 2 and 4 days, — 0.964 at 7 days. There was no significant difference in A value between 1 × 10-6 group and the control group (P gt; 0.05), while there were significant differences in A value between the control group and other concentration groups (P lt; 0.05). The growth curve of 1 × 10-6 group was similar to that of the control group, both had obvious phase of exponential growth. The growth curves of other groups had no obvious phase of exponential growth. The cytotoxicity of 1 × 10-6 group was classified as level 1, 2 × 10-6 group as level 2, 3 × 10-6 group as level 3, 4 × 10-6 group as level 3-4, 5 × 10-6 group and 10 × 10-6 group as level 4. Conclusion PAA of 1 × 10-6 had no obvious cytotoxicity. The residual l imit of PAA less than 1 × 10-6 was recommended.
Purpose To investigate retinoic acid (RA) induced apoptosis in retinal pigment epithelial (RPE) cells. Methods 10-5、10-6、10-7 mol/L were added to cultured PRE cells.Aridine orange fluorescence and TdT-mediated dUTP nick end labelling(TUNEL) techniques were used to observe apoptotic changes. Resultss 10-5、10-6、10-7 mol/L RA induced apoptosis in RPE cells.Cell shringkage,chromatin condensation and nuclear DNA fragmentation of RPE cells were observed by TUNEL technique.When 10-7、10-6、10-5mol/L RA treated RPE cells for 5 days,apoptotic index(AI)was 36.9%、4409% and 61.4% respectively,and 48.0%、59.9%、74.2% for 6 days.At the same concentration of RA,AI increased when time prolonged．At the same day,AI increased when the concentration of RA rose.There was significant difference in the results(Plt;0.05). Conclusion Our results showed that RA-induced apoptosis in RPE cells was detected with a good dose and time response. (Chin J Ocul Fundus Dis,1998,14:153-155)
ObjectiveTo explore the current situation of financial toxicity (FT) of breast cancer patients undergoing daytime chemotherapy under the background of diagnosis intervention packet (DIP) and its influencing factors, and to build a risk early warning model.Methods Convenient sampling method was used to select breast cancer patients undergoing chemotherapy in the daytime ward of Tianjin Medical University Cancer Institute & Hospital between April and May 2022. The general data questionnaire and FT comprehensive score scale were used to investigate them, and the influencing factors of patients’ FT were discussed through single factor analysis and logistic regression analysis, and the risk early warning model was established. Hosmer-Lemeshow fitting effect test was used to evaluate the prediction effect of the model.Results A total of 278 patients were included. The median (lower quartile, upper quartile) of FT score was 14.00 (8.75, 23.00), of which 195 patients (70.14%) had FT score≤22; 83 patients (29.86%) had FT scores>22. Logistic regression analysis showed that age, per capita monthly income of families, commercial health insurance, chemotherapy cycle, tumor stage, neoadjuvant chemotherapy were the influencing factors for high-risk FT of breast cancer patients undergoing daytime chemotherapy. The results of Hosmer-Lemeshow goodness of fit test showed that the model-predicted FT of breast cancer patients undergoing daytime chemotherapy was in good agreement with the actual observation value (χ2=10.685, P=0.220). The area under the curve of the model was 0.931 [95% confidence interval (0.900, 0.962)], the sensitivity was 0.807, and the specificity was 0.913.Conclusions The FT of breast cancer patients undergoing daytime chemotherapy is at a high level. Older age, purchase of commercial health insurance, and high per capita monthly income of families are protective factors for high-risk FT. The wind with chemotherapy cycle≤4 weeks, tumor stage Ⅱ, neoadjuvant chemotherapy are high-risk FT risk factors. The final warning model has been tested to have a good prediction effect, which can provide a reference for clinical medical staff to identify high-risk FT patients early and make preventive strategies as soon as possible.