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Since the approval of gemtuzumab ozogamicin, an antibody–drug conjugate (ADC) targeting CD33 in 2000, 13 ADC drugs have been approved by the FDA. Although these drugs have clearly improved the survival of patients with various types of advanced cancers, their significant toxicity has compromised their therapeutic benefits. The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities, where the payload drug is a determining factor. Antibody and linker may also affect the degree of toxicity. Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency, but treatment-related adverse reactions also increase accordingly. This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies, including but not limited to optimizing linker molecules, upgrading antibody design, and changing drug administration strategies, to improve the overall safety profile of ADC drugs.
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Objective:To observe the effect of astragalus polysaccharides on liver injury in mice with viral hepatitis,and to investigate whether it can regulate the expression of nucleotide-binding oligomerization domain 1(NOD1)/receptor-interacting protein 2(RIP2)/nuclear factor-κB(NF-κB)immune inflammation mediated by signaling pathway plays a protective role in liver.Methods:Sixty female C3H/HeJ mice were divided into modeling group(50 mice)and normal group(10 mice)using a random number table.The mouse model of viral hepatitis was established by intraperitoneal injection of mouse hepatitis virus type 3(MHV-3)in the modeling group.After the successful modeling was confirmed,the surviving mice were divided into thymus peptide group(10 μg),astragalus polysaccharide low,medium and high dose groups(100,200,400 mg/kg astragalus polysaccharide lyophilized in 1 ml/100 g body weight saline)and model group by random number table.Model group and normal group were given the same amount of normal saline intraperitoneal injection,each group was given once a day for 1 month.Results:The model was confirmed by HE staining of liver tis-sue and detection of viral plaque.Compared with the normal group,the liver index,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and tumor necrosis factor-α(TNF-α),IL-1β and IL-8,viral plaques in liver tissue,NOD1,RIP2 and NF-κB p65 expressions and p-NF-κB p65 level in the model group increased(P<0.05),and the liver tissue showed severe pathological changes.Compared with the model group,the liver indexes,serum ALT,AST,TBIL and TNF-α,IL-1β and IL-8,viral plaques in liver tissue,NOD1,RIP2 and NF-κB p65 expressions and p-NF-κB p65 level in the thymosin group and astragalus polysaccharide each 3-dose groups decreased(P<0.05),and the pathological changes of liver tissue were alleviated.The effect of astragalus polysaccharide was dose-dependent,and there were no significant differences in these indexes between thymosin group and astragalus polysaccharide medium dose group(P>0.05).Conclusion:Astragalus polysaccharides can improve the liver function of mice with viral hepatitis,reduce the inflammatory response and pathological changes of liver tissue,reduce the level of virus,specu-late and inhibit NOD1/RIP2/NF-κB pathway and down-regulate NOD1,RIP2 and NF-κB p65 expressions,inhibit p-NF-κB p65 level,and high dose of astragalus polysaccharide has the best effect,which is better than thymosin-α1.
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Objective:To study the chemical constituents in the dry roots of Rubus pinfaensis. Methods:The compounds were sep-arated from the alcohol extract of the roots of Rubus pinfaensis by silica gel column chromatography, and identified by IR, 1 H-NMR and EI-MS methods. Results:Five compounds were isolated and identified as oleanolic acid (Ⅰ) , 3-keto, 16α-hydroxy, 24-noroleanolic acid (Ⅱ) , 3′-methoxy myricetin (Ⅲ) , 2′-deoxyuridine (Ⅳ) and p-hydroxy phenylacetic acid (Ⅴ) . Conclusion: Compound Ⅰ,Ⅱ,Ⅲ,Ⅳ and Ⅴ are isolated from Rubus pinfaensis for the first time.
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Background:C-MET is expressed in a variety of tumor,and its expression may help to predict the prognosis of patients with gastric cancer. Aims:To explore the association of C-MET protein expression with survival in patients with stage Ⅲ gastric cancer. Methods:A total of 178 consecutive initially treated patients with stage Ⅲ gastric cancer from April 2010 to April 2014 at Beijing Pinggu Hospital were enrolled in this study. The expression of C-MET protein was determined by immunohistochemistry. Kaplan-Meier method was used to analyze the survival in patients with high C-MET protein expression and low C-MET protein expression,COX proportional hazards model was used to analyze the influence of various factors on prognosis. Results:C-MET protein was low expressed in 139 patients(78. 1%),and high expressed in 39 patients(21. 9%). Median survival(25. 1 months vs. 45. 0 months),1-year survival rate(69. 2% vs. 91. 4%),2-year survival rate(41. 0% vs. 84. 0%)were significantly decreased in high C-MET protein expression group than in low C-MET protein expression group(P all 0. 05). Conclusions:C-MET protein expression rate is 21. 9% in patients with stageⅢgastric cancer,C-MET expression is significantly associated with survival;1-year survival rate is lower in patients with high C-MET protein expression.
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Objective:To establish a method for the determination of organic residues ( hexane, benzene, toluene, xylene and sty-rene) in macroporous adsorption resins. Methods:Headspace-GC with a DB-624 column was used to determine the residues in macro-porous resins. The inlet temperature was 200℃ and the FID detector temperature was 240℃. The column temperature programming was as follows:the initial temperature was 40℃, maintained for 3 min, and then raised to 200℃ with the rate of 14℃/min and kept for 2 min. The solvent was methyl alcohol and the carrier gas was nitrogen. HPLC was applied to determine the contents of the five resi-dues. Results:The contents of the five organic residues were all below 20‰ in five macroporous resins in common use including D101, HPD100, AB-8, DM301 and NKA-9. Conclusion:The method is simple,accurate and reproducible. It can be used in the res-idue determination of macroporous resins.
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Objective:To study the optimal water extraction method for Shugan Xiaocuo granules. Methods: The study was car-ried out according to the orthogonal tablet. The water amount, extraction time,extraction times and soak time as the influencing factors, and the extractive yield and baicalin content as the indices in a comprehensive evaluation, the optimal extraction technology was screened. Results:The optimal extraction technology was as follows:soaked 30 minutes before cooking, 8-fold water,extracted for 3 times with 1h for every time. Conclusion:The verification test showed that the optimum extraction process was stable,reasonable and feasible.
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Objective To observe therapeutic effect of naoxintong on the patients with cerebral infarction.Methods 69 patients with cerebral infarction were randomly allocated to naoxintong group or control group. All patients were treated with 20ml shuxuening injection into veins and aspirin 100mg once a day, and those in naoxintong group were treated with naoxinting moreover. Neurological deficit scores (NDS) were evaluated before and after 1 month and 2 months of treatment Results Effective rate and notable effective rate of naoxintong group after 2 months of treatment were 97% and 88% ,obviously higher than those of control group 79% and 52%. Conclusion Nongxintong treatment for cerebral infarction was effective.
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Objective To investigate the value of obli que coronal MR images in visualization of the anterior cruciafe ligment(ACL).Methods Conventional axial,oblique sagittal and coronal MR images were performed in 30 normal knees.Then oblique coronal T 2-weighted i mages,which was parallel to ACL,based on oblique sagittal T 2 -weighted images ,were acquired.The visualization of ACL on oblique coronal,oblique sagital and coronal T 2-weighted images was analysed.Results The visualization of the whole ACL was 100%(30/30 ) on one image of the oblique coronal T 2-weighted images, 83.3%(25/30) on on e image of the oblique sagaital T 2-weighted image. On the coronal T 2-weighte d images,the ACL appeared as segmental bundle.The whole ACL could not be visua lized on one image of coronal T 2-weighted images.Conclusion The whole ACL can be showed on one image of ob lique coronal T 2-weighted image,which is helpful in evaluation of the injure o f ACL.