1.Advances in photodynamic therapy based on tumor hypoxia
Xiao-jie YIN ; Xiao-qian WANG ; Feng-ling ZHANG
Acta Pharmaceutica Sinica 2020;55(11):2618-2627
Photodynamic therapy (PDT) has attracted wide attention due to its unique advantages such as minimal invasiveness, high efficiency and high selectivity, and its ability to induce anti-tumor immune response. However, the treatment process is heavily dependent on the oxygen content of the treatment site, and the widespread oxygen deficiency in malignant tumors severely limits its efficacy. In addition, PDT-mediated oxygen depletion exacerbates tumor hypoxia, which further reduces its therapeutic effect. In recent years, many researches have been devoted to overcoming this problem. This paper summarized various strategies based on tumor hypoxic PDT in recent years, discussing the advantages and disadvantages of these strategies, and analyzing the main challenges and future directions of PDT in the treatment of tumors, so as to provide references for the in-depth study of photodynamic therapy of tumors.
2.Transhepatic arterial embolization-ablation therapy with Lipiodol-ethanol mixture for the treatment of VX2 liver cancer in experimental rabbits
Ting QIAN ; Maozhen CHEN ; Feng GAO ; Huabin YIN
Journal of Interventional Radiology 2014;(8):706-710
Objective To determine the optimal volume proportion of iodize d oil (Lipiodol)-ethanol mixture by comparing the clinical efficacy of transhepatic arterial embolization-ablation therapy using different volume proportion of Lipiodol-ethanol mixture in treating experimental rabbit models with VX 2 liver cancer. Methods VX2 tumor was implanted in eighteen adult male New Zealand white rabbits. The 18 VX 2 rabbit models were randomly and equally divided into the following six groups according to the Lipiodol-ethanol volume ratio ∶ group A (3 ∶ 1), group B (2 ∶ 1), group C (1 ∶ 1), group D (1 ∶ 2), group E (1 ∶ 3) and group F (1 ∶ 4). One week after the treatment, all the rabbits were sacrificed and their livers were removed and sent for pathologic examination. The tumor growth rate, the microvascular density, the apoptosis index (AI) of tumor tissues and the injury of the hepatic tissue adjacent to the tumor were evaluated. Results After the treatment, the tumor’s size was increased in group A, E and F. The tumor growth rate of group A was significantly higher than that of the other five groups , and the difference was statistically significant (P<0.05). The tumor’s size of groups B, C and D was decreased, although the difference was not significant when compared with the tumor’s size of groups E and F (P > 0.05). The proportion of ethanol in Lipiodol ∶ethanol mixture bore a negative relationship to the microvascular density counts (R2= 0.840, F = 89.432, P < 0.001). AI of group A was strikingly lower than that of groups C, D, E and F (P < 0.05). The difference in AI between group A and group B was not significant (P > 0.05), while the difference in AI between group B and group C or between group B and group F was statistically significant (P<0.05), and no significant difference in AI existed between each other among other groups (P > 0.05). The injury extent of the hepatic tissue adjacent to the tumor in group A and B was remarkably milder than that of other groups (P < 0.05). Conclusion When considered in terms of safety, the optimal volume proportion of Lipiodol-ethanol mixture should be 2 ∶ 1. Successful super-selective catheterization of the tumor feeding artery, strict and close fluoroscopic monitoring of the injection and proper increase in the proportion of ethanol can definitely improve the therapeutic efficacy.
3.Changes of Brain Metabolism in Obese Children Using Proton Magnetic Resonance Spectroscopy
ying, SUN ; fang-biao, TAO ; yin-feng, QIAN ; kun, HUANG
Journal of Applied Clinical Pediatrics 2006;0(19):-
Objective To explore whether obese adolescents had neurochemical abnormalities in frontal lobe and hippocampus.Methods Anthropometric indicators were measured in all participants.Proton magnetic resonance spectroscopy(1H-MRS)were performed in 9 obese adolescents and 9 non-obese children as controls.Spectral peaks of N-acetylaspartate(NAA),creatine(Cr),choline(Cho)of 2 cortexes were measured and their ratios were computed and compared.Results Values of NAA and Cho in frontal lobe in obese group were significantly lo-wer than those of controls.There was no significant difference of Cr,NAA/Cr,Cho/Cr in frontal lobe and hippocampus between 2 groups.Conclusion The reduced NAA and Cho on 1H-MRS suggests that amount of neural nerve and myelination of white matter may be harmed in frontal lobe of obese adolescents.
4.Advance on chemical compounds of Ainsliaea genus.
Fa-jin FENG ; Zhi-ling XU ; Qian-jun ZHANG ; Zhen-hua YIN ; Wen-yi KANG
China Journal of Chinese Materia Medica 2015;40(7):1244-1251
Plants in Ainsliaea genus, belongs to Compositae family, are traditional Chinese medicine and widely used in folk. These plants contain various types of chemical components, and main components are sesquiterpene lactone and its glycosides. In addition, there are triterpenoids, flavonoids, steroids, phenolic acid, long chain fatty acid and volatile oils. Recently, much attention has been payed to varlous research of A. fragrans. This paper reviewed and summarized the chemical components to provide the theoretical basis for the use of Ainsliaea.
Asteraceae
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chemistry
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Molecular Structure
5.Effects of laparoscopic and open D2 gastrectomy on the expression of interleukin-6 and interleukin-10 : a prospective analysis
Peng YIN ; Yan SHI ; Peiwu YU ; Feng QIAN ; Yongliang ZHAO ; Bo TANG ; Yingxue HAO
Chinese Journal of Digestive Surgery 2013;(5):358-361
Objective To compare the effects and significance of laparoscopic and open D2 gastrectomy on the expression of interleukin (IL)-6 and IL-10.Methods The clinical data of 146 patients with gastric cancer who were admitted to the Southwest Hospital from November 2010 to October 2011 were prospectively analyzed.All the patients were randomly divided into the laparoscopic group (75 patients) and open group (71 patients)according to the sealed envelope method.Laparoscopic or open D2 gastrectomy were performed according to the 14th edition of gastric cancer treatment guidelines of Japan Gastric Cancer Association.Peritoneal lavage fluid was collected at the beginning and the end of operation,and the concentrations of IL-6 and IL-10 in the peritoneal lavage fluid were detected by enzyme linked immunosorbent assay.The measurement data were analyzed using the t test,and the count data were analyzed using the chi-square test.Results The preoperative concentrations of IL-6 in the laparoscopic group and the open group were (34 ± 13)μg/L and (35 ± 12)μg/L,respectively,with no significant difference between the 2 groups (t =-5.110,P > 0.05).The postoperative concentrations of IL-6 in the laparoscopic group and the open group were (4015 ± 1592)μg/L and (6724 ± 2112)μg/L,respectively.The postoperative concentration of IL-6 in the laparoscopic group was significantly lower than that of the open group (t =-8.367,P < 0.05),and the postoperative concentrations of IL-6 were significantly higher than those before operation in the laparoscopic group and open group (t =-59.065,-87.123,P <0.05).The preoperative concentrations of IL-10 in the laparoscopic group and the open group were (43 ±9) μg/L and (42 ± 10) μL,respectively,with no significant difference between the 2 groups (t =1.190,P >0.05).The postoperative concentrations of IL-10 in the laparoscopic group and the open group were (92 ± 32)μg/L and (62 ± 23)μg/L,respectively.The postoperative concentration of IL-10 was significantly higher than that of the open group (t =6.408,P < 0.05),and the postoperative concentrations of IL-10 were significantly higher than those before operation in the laparoscopic group and the open group (t =-12.680,-6.802,P < 0.05).Conclusion Peritoneal inflammatory reaction is relatively lighter after laparoscopic D2 gastrectomy when compared with open D2 gastrectomy,which might prevent the peritoneal metastasis of gastric cancer mediated by IL-6.
6.Influence of Glucocorticoid on Bone Metabolism in Children with Tubercular Meningitis
feng-lian, ZHU ; gui-ling, FU ; jing, LI ; hui-yin, QIAN ; xue-peng, GUO
Journal of Applied Clinical Pediatrics 2004;0(08):-
0.05).The serum PICP of tubercular meningitis children after 4 neeks glucocorticoid therapy (108.85?46.13) ?g/L was significantly lower than that in control group((154.38)?47.98) ?g/L and glucocorticoid- pretreatment (152.99?44.78) ?g/L (P
7.Study on the function of infliximab in inducing remission in Crohn's disease and followed-up
Zhihua RAN ; Yan GU ; Jun SHEN ; Hongmin YIN ; Yuqi QIAO ; Meilan HUANG ; Feng ZHANG ; Xiaoxian QIAN
Chinese Journal of Digestion 2010;30(12):894-897
Objective To explore the function of infliximab in inducing remission in Crohn's disease and the effect of the inducing remission were followed up. Methods Ten patients with Crohn's disease received a infliximab, 5-aminosalicylic acid (5-ASA) and Azathioprine (AZA) therapy for inducing and maintenance remission. Crohn' s disease activity index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), apartate aminotransferase, (AST), total bilirubin (TBil), conjugated bilirubin, (CB), creatinine (Scr) were evaluated at week 0, 10, 22 and 50. Simple endoscopic score for Crohn's disease (SES-CD) were evaluated at week 0, 10 and 50. Adverse reactions were also evaluated. Results At week 10, all patients achieved remission. The indicators of CDAI, CRP, ESR and SES-CD were significantly declined than those at week 0 (P<0.01). The follow-up was terminated in one patient due to the relapse at week 30. At week 50, the indicators of CDAI, CRP, ESR and SES-CD in six patients a little bit increased compared with those at week 10, but no statistic significant (P=0. 2001、0. 0600、0. 1328、0. 4230 respectively), but significantly declined compared with those at week 0 (P =0.0005、0.0087、0.0054、0. 0163 respectively). No severe adverse reaction was observed in all patients.Conclusions Infliximab showed an exact efficacy in inducing remission in Crohn's disease. And 5-ASA and AZA were effective for maintenance remission in part of the patients after infliximab induced remission.
8.Amlodipine Improves Endothelial Progenitor Cell Mobilization and Neo-vascularization in Experimental Diabetic Rats After Myocardial Infarction
Li DONG ; Jiayin SUN ; Lina KANG ; Qian LUO ; Feng SUN ; Mingxia GU ; Xiaorong YIN ; Biao XU
Chinese Circulation Journal 2014;(9):718-722
Objective: To observe the effect of amlodipine on bone marrow endothelial progenitor cell (EPC) mobilization, neo-vascularization and cardiac function in diabetic rats after myocardial infarction (MI) with the possible mechanisms.
Methods: A total of 60 male SD rats were divided into 2 groups. Normal group, n=20. Diabetic group, n=40, the rats were fed with high fat diet (HFD) for 4 weeks and then received streptozotocin followed by left anterior descending coronary artery ligation to establish MI model, those rats were further divided into 2 sub-groups:Control group, the rats received sodium carboxymethylcellulose 1 ml/day with HFD and Treatment group, the rats received amlodipine 2 mg/kg/day with HFD, n=20 in each sub-group, all animals were treated for 4 weeks. The EPC level in peripheral blood CD45-/low+/CD133+/KDR+ at before and 1, 3, 5, 7, 14, 28 days after operation were examined by lfow cytometry, plasma vascular endothelial growth factor (VEGF) level was measured by ELISA, capillary density in MI area was determined by CD31 staining, EPC related protein expressions were detected by western blot analysis and the cardiac function was evaluated by echocardiography.
Results: EPC in CD45-/low+/CD133+/KDR+in Treatment group at 7 days after operation was increased than Control group at 5 days after operation (112 ± 30/106) vs (55 ± 10/106), plasma VEGF in Treatment group was higher than Control group (5.63 ± 1.33) ng/L vs (3.68 ± 0.98) ng/L; Treatment group presented increased expressions of protein kinase B, endothelial nitric oxide synthase (eNOS) and matrix metallopeptidase-9, increased capillary density in MI area, higher LVEF and left ventricular fractional shorting, all P<0.05-0.01.
Conclusion: Amlodipine improves EPC mobilization, neo-vascularization and cardiac function in diabetic-MI rats, it may be related to VEGF/eNOS cascade activation.
9.Insulation of cross-talk between signalingpathways-inspiration for innovative drug design
Li TAO ; Feng JIN ; Haibo WANG ; Yayun QIAN ; Yun SUN ; Yin LU ; Yanqing LIU
Chinese Pharmacological Bulletin 2017;33(7):900-904
Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.
10.Role of DNA topoisomerase II alpha in intrinsic and acquired drug resistance of liver cancer.
Qian-yu LI ; Yi WANG ; Zheng-feng YIN ; Feng-chao WU
Chinese Journal of Hepatology 2009;17(8):620-621
ATP-Binding Cassette, Sub-Family B, Member 1
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metabolism
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Antigens, Neoplasm
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biosynthesis
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genetics
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Antineoplastic Agents
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pharmacology
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Cell Line, Tumor
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drug effects
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Colorimetry
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DNA Topoisomerases, Type II
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biosynthesis
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genetics
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DNA-Binding Proteins
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biosynthesis
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genetics
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Drug Resistance, Neoplasm
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Epirubicin
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pharmacology
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Female
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Fluorouracil
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pharmacology
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Humans
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Immunohistochemistry
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Liver Neoplasms
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drug therapy
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metabolism
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pathology
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Male
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Middle Aged
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Predictive Value of Tests
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RNA, Messenger
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biosynthesis
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genetics