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Axl belongs to the family of receptor tyrosine kinase. Axl and its ligand Gas6 are aberrantly over-expressed in numerous human cancers. The binding of Gas6 and Axl could activate multiple signaling pathways,which take part in the development and progression of cancer,including cell survival,migration,invasion,and angiogenesis. In recent years,Axl and Gas6 have been considered as a promising novel target for cancer therapeutics. Several Axl inhibitors,including small-molecule tyrosine kinase inhibi?tors and anti-Axl monoclonal antibodies are currently under research. In this paper ,we review the development of Axl-targeting drugs in tumor therapy.
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OBJECTIVE To investigate the effect of amifostine(Amf)on the differentiation of human megakaryocyte cell line-Dami. METHODS Dami cells were treated with Amf 0.01-5.0 mmol · L-1 for 12 d. Dami cells were counted every day for the growth curve:only cells with a diameter>20μm. The platelet demarcation membrane system was observed by transmission electron microscopy. The expression of CD33,CD34,CD41a and DNA ploidy was detected by flow cytometry. RESULTS Amf 0.1-1.0 mmol · L-1 promoted the differentiation of Dami cells ,but inhibited their proliferation at a concentration>1.0 mmol · L-1. When these cells were treated with Amf 1.0 mmol · L-1 for 12 d,the platelet demarcation membrane system was observed,the percentage of cells with a diameter >20 μm was increased by 24.6%(P1.0 mmol·L-1).
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Objective To develop a human Tim-3 specific monoclonal antibody and evaluate its biological activity and possible use in clinical diseases associated with dysregulated Tim-3 expression .Methods The BALB/c mice were immu-nized by conventional method, and positive clones were used to develop anti-human Tim-3 antibody, the binding and neutralization activities of which in vitro and in vivo were investigated.Results ①A monoclonal antibody (clone L3D) which could specifically bind to human Tim-3 protein in ELISA assay was obtained and the subtype of the monoclonal antibody was IgG2a .②Flow cytometry indicated that the monoclonal antibody could bind to Tim-3 expressed in human U937 cells.This antibody also showed a cross activity to mice′Tim-3.③The monoclonal antibody inhibited the apoptosis of THP1 cells induced by Gal-9, the ligand of Tim-3.④Injection of Tim-3 antibody exacerbated sepsis in mice as marked by the decreased survival rate and increased expression of pro-inflammatory cytokines .Conclusion An anti-human Tim-3 monoclonal antibody is successfully obtained.The excellent binding and neutralization activities of this antibody enable it to be widely used in clinical diseases associated with deregulated Tim-3 expression .
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Objective To evaluate the technique and efficacy of minimally invasive percutaneous nephrolithotomy (MPCNL) for renal calculi in pediatric patients. Methods From April 2009 to December 2009, 12 pediatric patients (8 males and 4 females) with renal calculi were treated by MPCNL. The age ranged from 18 to 53 months (mean 32 months). All the 12 cases were diagnosed by KUB+IVU, ultrasonography and CT. The stone had average diameter of 1. 3 cm (ranged from 1. 0 to 1. 8 cm). Seven cases had simple renal pelvis stone and 5 cases had multiple renal calyx stone. UPJ stricture was not found in this series. General anaesthesia was applied. Renal transfixion pin was punctured to select renal calices by monitoring with ultrasonography. 12 - 16 F percutaneous renal access was successfully established in all cases and calculi were fragmented by pneumatic lithotripter. Results The average operative time of MPCNL was 74 min. Phase Ⅰ lithotripsy was underwent in all patients. The phase Ⅰ stone-free rate was 67%(8/12). One cases accepted second MPCNL. The calculus clearance rate reached 75%(9/12). Three cases had residual calculi ranged from 2 to 4 mm. One of whom had ESWL 2 weeks postoperatively. All cases were followed up for 1 - 7 months, all cases were in stone free status. Conclusion Regarding the advantages of less bleeding, high clearance rate, and shorter hospital stay, MPCNL is an effective and safe treatment option for renal calculi in pediatric patients.
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Objective To explore the comprehensive therapy of infants with urinary calculus induced by melamine.Methods Clinical data of 228 infants(aged from 4 months to 3 years,mean age 11 months)with urinary calculus induced by melamine were analyzed. Bilateral renal calculi were found in 144 cases and one-side renal calculus in 54 cases,of which the diameter ranged from 0.5-2.5 cm.Ureteral calculi with moderate to severe hydronephrosis were found in 15 cases,of which the diameter ranged from 0.4-1.1 cm. Bladder calculi with urinary retention were found in 5 cases and urethral calculi with urinary retention in 10 cases,of which the diameter ranged from 0.5-1.3 cm. All the urinary calculi were confirmed by B-uhrasound examination and CT. Group 1 : Of the 15 cases with acute renal failure, 13 underwent shattering and dissolving renal and ureternal calculus by pelvis clysis with alkalinity drug, detaining double J tubes through ureteroscope. After operation, these patients were treated with alkalinity drugs. Two cases were treated by percutaneous nephrostomy guided by B ultrasound and underwent shattering and dissolving renal calculus by intermittent pelvis clysis with alkinity drug. Group 2:15 cases of ureteral calculus with serious nephrohydrops underwent shattering and detaining double J tubes through ureteroscope, then treated with alkalinity drug. Group 3:15 cases of infant bladder and urethral caleus with acute urinary retention were treated by EMS through ureterscope per urethra. Group 4: The rest 183 cases without urinary obstruction received 1-8 week'surine alkalization therapy. Among them, 113 cases received sodium bicarbonate 0.15 g twice per day,23 cases received potassium sodium hydrogen citrate 2.4g/d, and 47 cases received 10% potassium citrate solution 5 ml 3 times per day. Sixty-one cases who were of no effect with alkalinity drug were treated by extracorporeal shock wave lithotripsy (ESWL) and dissolving calculus with sodium bicarbonate. During treatment with alkalinity drug, urine Ph was observed by urine analysis once per day.When it exceeded 7.5, alkalinity drug. Was withdrawn. All the patients were followed up for 1 to 3 months. Statistical analysis was done with the SPSS 13.0 software. ResultsHyperdiuresis emerged 12-24 h after operation in group 1. The duration of hyperdiuresis was 24-72 h with the urine volume of 800-2500 ml/24h. Urine volume revived gradually 48--96h after operation while serum BUN and Cr revived 1-5 d after operation. Four cases with renal and ureteral calculus became almost stone-free in 1-2 weeks and 14 cases became completely stone-free in 2-4 weeks after operation. Patients of group 2 became completely stone-free in 1-2 weeks. Patients of group 3 were cured by one EMS session through ureterscope per urethra and smooth urination was seen immediately after operation. No retained calculus in the bladder and urethra was found by B ultrasound 3 days later. In the sodium bicarbonate group, 4 cases became completely stone-free in 2 weeks, 18 cases in 4 weeks, 15cases in 13 weeks. The stones lessened and faded in 34 cases and had no changes in 42 cases. In the potassiun sodium hydrogen citrate group, 4 cases became completely stone-free in 1 weeks, 7 cases in 2 weeks, 10 cases in 4 weeks, 2 cases in 6 weeks. In the potassium citrate group, 3 cases became completely stone-free in 1 weeks, 5 cases in 2 weeks, 16 cases in 4 weeks, 11 cases in 8 weeks. The stones lessened and faded in 8 cases in 8 weeks and had no changes in 4 cases. The efficacy of the sodium bicarbonate group was significantly different with the efficacy of the citrate group (P=0. 001). No significant difference was found between the potassium sodium hydrogen citrate group and the potassium citrate solution group(P=0. 372). ConclusionsConservative treatment should be employed mainly in the earlier stage for the infant urinary calculus induced by melamine . When the diagnosis of acute renal failure, moderate to severe hydronephrosis and acute lower urinary tract obstruction are established, surgical intervention should be the main method to relieve obstruction, protect renal function and resume normal rnicturition. With the development of the characteristics of the stones later,the oral dissolution therapy with alkalirtity drug could not dissolve the calculi and ESWL should be employed.
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Objective To evaluate the efficacy and safety of direct renal chemolysis with alkaline drug through ureteral catheter or nephrostomy tube for the treatment of infantile renal calculus resul-ted from melamine. Methods Fifteen infants of acute post-renal failure resulted from bilateral renal calculi were treated. The age of the infants was 5--12 months(average, 9 months). Stone size varied from 0.4 to 1.5 cm (average, 0.8 cm). They were all fed on milk powder polluted with melamine for a long time and diagnosed with acute post-renal failure based on the imaging and chemical examination. Double-J stents insertion by ureteroscope was performed on 13 infants and direct renal chemolysis with alkaline drng(5% NaHCO3,20 ml)through ureteral catheter was performed during operation. Percuta-neous nephrostomy was performed on 2 infants to remove the obstruction of upper urinary tract and di-rect renal chemolysis with alkaline drug(1.4% NaHCO3, continuous perfusion by gravity) through ne-phrostomy tube was performed intermittently after operation. Results Direct renal chemolysis was performed successfully on the 15 infants. The urine volume recovered in 2--5 d, blood urea nitrogen and serum creatinine recovered in 2--3 d postoperatively. During the operation of the infants treated by direct renal chemolysis with 5%NaHCO3 throuth ureteral catheter, a large number of limous fluid spurted from ureterostoma. According to CT examination 2 weeks after operation, the stone frag-ments were removed thoroughly in 13 infants, the diameter of the stone lessened more than 50% in 2 infants. Conclusion Direct renal chemolysis with alkaline drug for eliminating infantile renal cal-culus resulted from melamine is sale and effective.
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Objective To investigate the clinical application of ureteroseope in the treatment of infant renal calculus with acute post-renal failure. Methods Thirteen cases of infant renal calculus with acute post-renal failure included 11 males and 2 females aging from 5 months to 1 years with a mean age of 9 months. Five cases showed bilateral renal calculi with hydronephrosis, 3 cases showed one side renal calculus with eontralateral uretal calculus incarceration, 3 cases showed bilateral uretal calculus incarceration, 2 cases showed bilateral renal calculi and hydronephrosis with urinary calculi. Anuria appeared in 11 cases for 1-3 d while oliguria appeared in 2 cases for 5-10 d. BUN and SCr were higher than normal level in all cases. Hyperuricemia was found in 8 cases, hyperkaliemia was found in 9 cases, pH values in urine of all infants were less than 6. 5(mean, 5. 5). Radiopague stone was not found in all cases by KUB. Hydronephrosis was found in 13 cases, and the diameter of hydro-nephrosis in 9 cases was more than 2.5 cm by B ultrasound. All cases were diagnosed as urinary stones with the diameter from 0.5 to 1.5 cm by CT. All cases were inserted with double J stents un-der ureteroscope for internal drainage, crushing, rinsing and eliminating stones. Results Hyperdi-uresis emerged within 24 h after operation in 13 patients. The duration of hyperdiuresis was from 24 h to 72 h. Urine volume revived gradually 48-96 h after operation while BUN and SCr revived 1-5 dafter operation. Serum uric acid revived 1-7 d after operation in 8 cases of hyperuricacidemia. Serum potassium revived 1-3 d after operation in 9 cases of hyperpotassaemia. Double J tubes were detained for 2-4 weeks. Renal calculus in 10 cases were found by B ultrasound to be discharged and conse-quently double J tubes were pulled out. Renal calculi in 2 cases became smaller and lighter. Conclu-sions For infant renal calculus with acute post-renal failure, upper urinary obstruction could be re-lieved immediately with revived urination and improved renal function by dissolution and crushing of calculus, and the placement of double J tube for internal drainage under ureteroscope. This operation is safe, high-efficient with less lesion, and would be the first option to relieve obstruction for infant re-nal calculus with acute post-renal failure.
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Objective To evaluate the effect of EMS through ureteroscope per urethra for the treatment of infant bladder and urethral stone with acute urinary retention. Methods Ten cases (9 boys, 1 girl)of infant bladder and urethral stone with acute urinary retention were treated by EMS through ureteroscope per urethra. Mean age of the patients was 9 months. Two cases suffered from bladder stones while the other 8 cases suffered from urethral stones. The size of stones varied from 0.5-1.1 cm with the average of 0.8 cm. All 10 cases underwent EMS through ureteroseope per ure-thra after general anaesthesia by using ketamine in vein. Wolf F8/9. 8 ureteroscope was used and mo-nitored by television. The EMS probe of ultrasound lithotripsy was sticked through operating passway of ureteroscope to shatter and eliminate bladder and urethral stone. During operation, 50-- 100 ml li-quid pressure was retained in the urinary bladder. The pressure of perfusion pump varied between 160 and 210 kPa(average, 180 kPa). The energy of ultrasound lithotripsy was 40%--60% with a ratio of 30%--70%. F8 type of 2 cavity aerocyst urethral catheter was indwelled after operation. Results The average operation time was 25 min. Urethral stones were rinsed into bladder. Stones were elimi-nated at one time by ureteroscope. Urethral catheters were removed after the patients revived from anesthesia and smooth urination was seen immediately after operation. No retained calculus in the bladder and urethra was found by B ultrasound 3 days later. Conclusions Low urinary obstruction could be relieved immediately after EMS through ureteroscope per urethra in patients of infant bladder and urethral stone with acute urinary retention. This operation is safe, high-efficient with less lesion, and would be the first option for the patients of infant bladder and urethral stone with acute urinary re-tention.