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Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.
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Objective To compare the clinical effects and safety between laparoscope radical surgery after neoadjuvant chemoradiotherapy and traditional surgery alone for treatment of rectal cancer patients. Methods A total of 122 patients with rectal cancer from January 2013 to January 2015 in Qingdao Tumor Hospital were divided into the observation group (61 cases) and the control group (61 cases) according to the different therapies. The patients in the observation group received laparoscope radical surgery after neoadjuvant chemoradiotherapy, and the patients in the control group received laparoscope radical surgery of rectal carcinoma. The operative, pathological, immunological indicators and the complications were analyzed retrospectively. Results There were no statistical differences in conversion to open laparotomy rate [6.6 % (4/61) vs. 4.9 % (3/61)], anus preservation rate [80.3 % (49/61) vs. 67.2 % (41/61)], radical rate [77.0 % (47/61) vs. 85.2 % (52/61)] in the observation group and the control group (χ2: 0.152, 2.711, 1.339 respectively, all P > 0.05). The proportion of terminal ileum in the observation group was significantly higher than that in the control group [60.3 % (38/61) vs. 21.3 % (13/61), χ 2= 21.058, P < 0.05]; the number of cleaned lymph nodes in the observation group was significantly lower than that in the control group (8±5 vs. 15±7, t= 5.834, P < 0.05). There were no significant differences between before the treatment and 7 d after surgery of the two groups in the levels of T cells, CD4+, CD8+, CD4+/CD8+and natural kill cells (P > 0.05). There were no significant differences between the observation group(24.6 %)and the control group(27.9 %)in postoperative complication rates (P> 0.05). Conclusion Laparoscope radical surgery after neoadjuvant chemoradiotherapy can reduce the number of lymph nodes dissection with low incidence rate of postoperative complications and implicit impacts on immune system,which is safe and worthy of wide application.
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Objective To detect the expressions of osteopontin (OPN) and inerleukin-18 in patients with bullous pemphigoid (BP),and to analyze their relationship with clinical and laboratory indices.Methods Enzyme linked immunosorbent assay (ELISA) was performed to quantify the serum levels of osteopontin (OPN) and inerleukin (IL)-18 in 30 patients with BP and 30 health controls.Results The serum level of OPN was statistically higher in the patients than in the healthy controls ((8.29 ± 2.76) vs.(3.88 ± 1.41 ) ng/ml,P ＜ 0.01 ),and was positively correlated with the severity of BP (r =0.658,P ＜ 0.01 ) and with some laboratory indices in the patients.Increased serum IL-18 level was observed in patients complicated by cardiovascular diseases compared with those without cardiovascular diseases ((37.49 ± 6.43) vs.(31.10 ± 5.40) pg/ml,P ＜ 0.01).Moreover,the BP patients with diabetes,tumor,hepatic and renal impairment displayed an enhanced level of serum OPN and IL-18 than those without (all P ＜ 0.05).Conclusions OPN may be positively correlated with the severity of BP,while IL-18 may be involved in the development of complications of BP.