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Objective Bevacizumab ( BM ) is an angiogenesis inhibitor widely used in cancer therapy, but its off-target effect of proteinuria may lead to discontinuation of treatment.This study was to explore the mechanisms of BM inducing proteinuria in mice. Methods Twenty-four healthy mice were randomly divided into four groups, saline control, low-dose BM, medium-dose BM, and high-dose BM, treated by injection of normal saline and BM at 10, 35, and 60 mg per kg of the body weight, respectively, though the tail vein.At 4 weeks after injection, 24-hour urine was collected to determine the total urine protein and blood obtained from the eyeballs for biochemical analysis.Then all the mice were sacrificed and the kidneys harvested for observation of pathologic changes in the glomeruli as well as for immunohistochemistry, Western blotting, and real-time PCR analysis. Results Compared with normal saline,BM obviously elevated the level of 24-hour urine protein, with statistically significant differences between the control and the medium-and high-dose BM groups (0.23 ±0.02 vs 1.14 ±0.13 and 1.43 ±0.10, P0.05).No significant differences were observed among the four groups in the levels of Cr, BUN, AST and ALT (P>0.05).Under the optical microscope, the kidneys showed normal structures in the control group, no signifi-cant pathologic changes in the low-dose BM, and vacuolus-like alteration with atrophic glomerular endothelial cells in the medium-and high-dose BM groups.Immunohistochemical analysis demonstrated the expressions of VEGF and podocin were moderately or strongly positive in the control and low-dose BM groups, by weakly positive or negative in the medium-and high-dose BM groups.Compared with the control group, the expression of the VEGF protein in the renal tissue was significantly decreased in the high-dose BM group (0.76 ±0.09 vs 0.39 ±0.05, P0.05), and the expression of the podocin protein was significantly reduced in the medium-dose BM (0.67 ±0.07 vs 0.43 ±0.10, P0.05).The mRNA expressions of VEGF and podocin were not significantly changed in the low-dose BM group as compared with the control (1.07 ±0.61 and 1.12 ±0.09 vs 1.23 ±0.25 and 1.17 ±0.19, P>0.05) but remarkably de-creased in the medium-dose (0.82 ±0.38 and 0.71 ±0.18) and high-dose BM groups and (0.47 ±0.64 and 0.42 ±0.09) groups (P<0.01). Conclusion Bevacizumab damages glomerular filtration membrane and induce proteinuria partially by down-regulating the protein and mRNA expressions of VEGF and podocin.
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Raltitrexed is a specific inhibitor of thymidylate synthase,and has been confirmed that ralti-trexed has no cross tolerance with 5-fluorouracil.Studies have shown that raltitrexed-based combination chemo-therapy has a beneficial effect on the treatment of advanced gastric cancer,and well tolerance,which is worthy of clinical use.
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Objective To study the technology and the result of dual plane breast augmentation using nipple margin vertical incision of areola.Methods Totally 60 cases of augmentation mammaplasty were involved in this study.The nipple margin vertical incision of areola was applied obliquely into the breast through the pectoralis major fascia.The rib starting point of pectoralis major were cut off,medial to the side of the sternum.Under the pectoralis major the cavity was peeled according to the preoperative design range.Based on the different situation of the breast types Ⅰ,Ⅱ,Ⅲ,dual plane breast augmentations were stripped respectively.After implanting the breast prosthesis,the upper part of the prosthesis was under the pectoralis major and the lower part was under the mammary gland.Results The 60 patients were all after childbearing,20 of whom underwent type 2 dual plane breast augmentation,4 underwent type 3 double plane and the rest underwent type 1 double plane.After 3 months to 2 years follow-up,all cases got satisfactory results,except 1 case of postoperative hematoma and 1 case appeared capsular contracture.Conclusions The nipple margin vertical incision of areola can complete types Ⅰ,Ⅱ,Ⅲ dual plane breast augmentation operation,at the same time it can correct mild-to-moderate mastoptosis.
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Objective Antiangiogenesis therapy has been shown to prolong survival for patients with malignant tumor .However the present study has not been observed the clinical benefit of antiangiogenesis therapy combination with chemotherapy treated with gastric canc-er.Human recombinant vascular endothelial inhibition (endostar) as a multi-targeted anti-angiogenesis drug, the mechanism is different from other Antiangiogenesis drugs.It can block different pathways of signal transduction to inhibit angiogenesis .This study aimed to observe the effect of combined application of endostar and paclitaxel on biological behavior of gastric cancer cell lines . Methods MMT assay and Tr-answell invasion assay were respectively used to examine the inhibition rate of cell growth and invasion ability when cells were treated with va-rious concentrations of endostar and paclitaxel alone or in combination.The protein expressions of VEGF,MMP-2 and MMP-9 were examined by Western blot. Results Endostar or paclitaxel effectively inhibited the growth of MGC803 cells and the in vitro invasion of MGC803 cells in a concentration-dependent manner.The proliferation and invasion ability of combined treatment with endostar and paclitaxel was significantly lower than that of endostar or paclitaxel alone (P<0.05).Compared with con-trol group, the VEGF,MMP-2 and MMP-9 protein expressions were de-creased in experimental groups ( P <0.05).Compared with paclitaxel group, the VEGF, MMP-2 and MMP-9 protein expressions were relatively reduced in combination groups (P<0.05). Conclusion Endostar combined with paclitaxel can suppress the growth and invasion of MGC803 cells, and the decreasing VEGF , MMP-2 and MMP-9 expressions may be involved in the mechanism .
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Objective To explore the methodology of suturing the upper margin of the orbicularis muscle in pretarsal orbicularis myocutaneous flap to the levator aponeurosis,simulating the mechanism of fibers from the levator aponeurosis to the dermis in natural double-eyelid in blepharoplasty.Methods Pretarsal orbicularis myocutaneous flap was harvested.Dissection between the orbital septum and the levator aponeurosis was performed originating from the upper margin of the tarsi until to the levator muscle.The upper margin of the orbicularis muscle in pretarsal orbicularis myocutaneous flap was sutured to the levator aponeurosis.The lower skin margin to the orbital septum to the upper skin margin was sutured interruptedly.Patients with medial epicanthus were performed epicanthoplasty at the same time.Results 136 eyes in 68 patients were performed with double-eyelid blepharoplasty using this method.62 patients were followed-up for 1 month and 53 patients were followed-up for 3 months.They all reported satisfactory aesthetic results.Conclusions Double-eyelid blepharoplasty using this method accords with the physiological mechanism in natural double-eyelid.Postoperative double-eyelid is natural with little tumefaction.This method can avoid double-eyelid fold retraction and multi-fold occurrence.
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Objective To observe the k-ras mutation rate of colorectal cancer in China, and assess the effect and toxicity in advanced colorectal cancer (CRC) patients (pts) receiving chemotherapy combined with monoclonal antibody against Epidermal Growth Factor Receptor (EGFR). Methods The k-ras mutation of 139 samples collected from our hospital were tested by pyrophosphoric acid sequencing. Twenty-three advanced colorectal cancer patients were treated with chemotherapy combined with anti-EGFR monoclonal antibody, including 3 initial treated and 20 retreated. In the total 23 patients, 18 were treated with cetuximab and chemotherapy, and S were treated with nimotuzumab and chemotherapy. Cetuximab was taken with 400 mg/m2 first time, and then 250 mg/m2 every week. Nimotuzumab was taken with 400 mg first time, and then 200 mg every week. Eight patients of the total 23 received anti-EGFR monoclonal antibody combined with irinotecan, 12 with FOLFIRI, 3 with FOLFOX4. Results k-ras mutation type (mt) was detected in 39.6 % (55/139) of pts, k-ras wild type (wt) was 60.4 % (94/139). In 22 effect evaluable patients, 5 received PR and 9 SD, and RR and DCR were 22.7 % and 63.6 %, respectively. TTP was 124 days. Thirteen of the 22 patients tested k-ras mutation, of the 11 k-ras mt pts, 4 received PR, 4 SD and 3 PD. Two patients of k-ras mt received PD after 2 cycles treatment. Acneform eruptions were observed in 15 patients of 18 pts who received cetuximab and paronychia in 3 pts. Eruption or paronychia was not observed in all patients who received nimotuzumab. Grade 3 hypersensitivity were occured in 2 patients with cetuximab, and one of them alternated nimotuzumab in next cycle didn't get hypersensitivity any more. Conclusion The mutation rate of k-ras in Chinese colorectal cancer patients was similar with westerners. The effect of cetuximab combined with chemotherapy on advanced colorectal cancer was reliable. Nimotuzumab combined with chemotherapy worth to be studied further because of the promising effect and mild toxicity.
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Objective: To compare the efficacy and safety of different administration of pamidronate for relieving bone pain and to improve the living quality in Chinese patients with painful bone metastases due to lung cancer. Methods:96 patients with painful bone metastases due to lung cancer were randomly enrolled to group A (150 mg) or group B (90 mg). There were 53 patients receiving 150 mg of pamidronate(34 pts for 2 days and 19 patients for 5 days administration). 43 (patients) receiving 90 mg of pamidronate. Results:There were 84.9% of patients relieving bone pain in group A and (67.4%) in group B (P=0.043). The score measuring bone pain decreased from 6.47?1.45 to (3.28?)1.71 in group A and from 6.21?1.49 to 3.49?2.88 in group B after injection of pamidronate , and the mean duration for pain relief were 28.00 days and 21.00 days respectively(P
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Objective To observe the short-term efficacy and toxicity of HEPP regimen in treatment of refractory Non-Hodgkin's Lymphoma. Methods HEPP regimen: HCPT 8 mg/m2 iv gtt d1~ d5, VP16 100 mg/d iv gtt d1~d5, PDD 20 mg/d iv gtt d1~d5, PDN 60 mg/m2 po d1~d14. The chemotherapy was repeated every 4 weeks as a cycle.The clinical effect was evaluated after 2 cycles and toxicity was observed during every cycle. Results 25 patients were eligible for toxicity evaluation and 22 patients for clinical response evaluation. The objective response rate was 60.0 %, including three cases complete remission and ten cases partial remission. Six cases achieved stable disease and three cases progressive disease. The major toxicity was bone marrow suppression, including 24.0 % grade Ⅲ/Ⅳ leukopenia and 12.0 % grade Ⅲ/Ⅳ thrombocytopenia. The incidence of nausea/vomiting, mucositis and hepatic toxicity was low. Conclusion HEPP regimen can achieve a satisfy result in the treatment of refractory Non-Hodgkin's Lymphoma. It is low toxic and well tolerated.