1.Random and control study comparing gemcitabine administered in fixed dose rate with a more standard infusion combined with oxaliplatin regimens in advanced biliary tract cancer patients
Yiyuan WAN ; Hongxia HUI ; Xiaowei WANG ; Hua LIU
Chinese Journal of Clinical Oncology 2014;(17):1098-1102
Objective:To investigate and compare the effects of oxaliplatin combined with gemcitabine administered in a fixed dose rate and that administered in a more standard infusion in advanced biliary tract cancer patients on chemotherapeutic efficacy, toxicities, and survival time. Methods:A total of 93 cancer patients were recruited from February 1, 2010 to December 12, 2012 in the First Hospital of Huai'an City Affiliated Nanjing Medical College. Those recruited were either newly diagnosed unresectable advanced biliary tract cancer patients by percutaneous liver biopsy or relapse or metastatic biliary tract cancer patients after operation. The patients were randomly divided into two groups. The first group was the study group in which the patients received chemotherapy with gemcitabine in a fixed dose rate of 10 mg/m2 per minute combined with oxaliplatin regimens. The other group was the control group in which the patients received chemotherapy with gemcitabine in a more standardized infusion within 30 min combined with oxaliplatin regimens. Each patient received four cycles, with at least two cycles of chemotherapy with GEMOX regimens every 21 d, with follow-up until death. The chemotherapeutic efficacy was evaluated. Toxicities were documented after each cycle. Results:The clinical characteristics of the two groups were well balanced before chemotherapy (P>0.05). The response rate (RR) and clinical benefit response of the study group were higher than those of the control group (P<0.05). The overall survival (OS) and time to progress (TTP) of the study group were longer than those of the control group (P<0.05). With respect to adverse events, the major side effect was hematological toxicity. The rate of gradeⅢ/Ⅳleucocytopenia and thrombocytopenia in the study group was remarkably higher than that in the control group (P<0.05). However, the rate of non-hematological toxicity was similar (P>0.05). Conclusion:Gemcitabine in a fixed dose rate combined with oxaliplatin regimens is a feasible and effective scheme in treating advanced biliary tract cancer patients. RR is higher and OS and TTP are longer under this scheme. Non-hematological toxicities are also well tolerated. However, hematological toxicity is distinguished. These results guide us to be prudent in utilizing this regimen. The investigation of the value of gemcitabine in a fixed dose rate combined with oxaliplatin in treating advanced biliary tract cancer patients is worth pursuing in future clinical trials.
2.Clinical study of prevention of oxaliplatin-induced acute neurotoxicity by calcium and magnesium infusions
Jian-Hua YU ; Hui-Ping WAN ; Jian-Yong YU ;
Cancer Research and Clinic 2000;0(06):-
Objective To evaluate the efficacy of calcium(Ca)and magnesium(Mg)infusions in pre- vention of oxaliplatin-induced acute neurotoxicity.Methods Fourty-two patients with advanced colorectal carcinoma were eligible for the study:21 were assigned to the Ca/Mg ann and 21 to the control arm.The Ca/ Mg arm and the control arm were comparable for patients'characteristics.Chemotherapy regimen were al- most the same in both arms.Chemotherapy regimen consisted of oxaliplatin 130 mg/m~2 on day 1,given as a 3-hour infusion in 500 ml of 5% glucose,concurrent with rahitrexed 3 mg/m~2 as a 15-minute intravenous (Ⅳ)infusion or calcium folinate(CF)200 mg?m~(-2)?d~(-1),days 1~5,5-Fluorouracil(5-Fu)500 mg?m~(-2)?d~(-1),days 1~5.Therapy was repeated every 3 weeks.The treatment consisted of Ca gluconate and Mg sulfate,1 g each, delivered i.v.over 15 min just before the oxaliplatin infusion and repeated at the same dose after the comple- tion of the oxaliplatin infusion.A specific neurotoxicity scale was used for oxaliplatin-related neurotoxicity. Results Ten patients(47.62%)had acute neurotoxicity in the Ca/Mg arm compared with 19 patients (90.48%)in the control arm(P0.05).Conclusion Ca/Mg infusions seem to reduce incidence and intensity of oxaliplatin-induced acute neurotoxicity,and they do not reduce the clinical activity of oxaliplatin,but dosage and administration schedule could be optimized.
3.Effect of stromal cell derived factor-1αand interleukin-1βon inducing vascular endothelial cells expressing lymphatic phenotype
Ning SUO ; Xueying WANG ; Chunlin YANG ; Hui ZHOU ; Fei LI ; Zongpu ZHANG ; Fangzhu WAN ; Hua TIAN
Acta Anatomica Sinica 2014;(3):388-392
Objective To investigate the effect of stromal cell-derived factor-1α( SDF-1α) and interleukin ( IL-1β) on inducing vascular endothelial cells to express lymphatic phenotype .Methods The CRL-1730 cell line was cultured and treated with SDF-1αor IL-1β.The expression of endothelial cell markers and lymphatic endothelial cell markers were investigated with Real-time PCR, Western blotting and immunocytochemistry .Results In CRL-1730 cell line, endothelial cell markers such as voln willebrand factor ( vWF ) , VE-cadherin , vascular endothelial growth factor receptor(VEGFR)2, were dose dependently down-regulated after SDF-1αstimulation, while lymphatic phenotypes such as Prox-1, podoplanin and lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1), were dose-dependently up-regulated after SDF-1αstimulation.The changes of vWF, VEGFR2 and podoplanin, Prox-1, LYVE-1 expression after IL-1βstimulation was similar to that after SDF-1αwhile expression of VE-cadherin changed slightly .Conclusion SDF-1αand IL-1βare able to induce vascular endothelial cell expressing lymphatic phenotype .
4.Automated assessment of developmental levels of epiphysis by support vector machine.
Ya-hui WANG ; Zi-shen WANG ; Hua WEI ; Lei WAN ; Chong-liang YING ; Guang-you ZHU
Journal of Forensic Medicine 2014;30(6):422-426
OBJECTIVE:
To realize the automated assessment of the levels of epiphysis of distal radius and ulna by support vector machine (SVM).
METHODS:
The X-ray films of the left wrist joints were taken from 140 teenagers aged from 11 to 19 years old as training samples. The levels of epiphysis of distal radius and ulna were divided into five developmental levels. Each level contained 28 samples. Another 35 cases were selected as independent verifying samples. SVM classification models of the five developmental levels of epiphysis of distal radius and ulna were established. The internal cross validation was made by leave one out cross validation (LOOCV), while the external validation was made by histogram of oriented gradient (HOG), and then the accuracy (PA) of testing results was calculated, respectively.
RESULTS:
The PA of SVM, LOOCV and HOG of distal radius epiphyseal level were 100%, 78.6%, and 82.8%, respectively; whereas the PA of SVM, LOOCV and HOG of distal ulna epiphyseal level were 100.0%, 80.0% and 88.6%, respectively.
CONCLUSION
The SVM-based automatic models of the growth stage of distal ra- dius and ulna appear to have certain feasibility, and may provide a foundation for software development of bone age assessment by forensic medicine.
Adolescent
;
Bone Development/physiology*
;
Child
;
Epiphyses/growth & development*
;
Female
;
Humans
;
Image Processing, Computer-Assisted/methods*
;
Male
;
Radius/growth & development*
;
Support Vector Machine
;
Ulna/growth & development*
;
Wrist/growth & development*
;
Wrist Joint/growth & development*
;
Young Adult
5.Research progress in drugs targeting tumor associated macrophage
Li-wen REN ; Yi-hui YANG ; Wan LI ; Yi-zhi ZHANG ; Hong YANG ; Sen ZHANG ; Fang XU ; Yue HAO ; Wan-xin CAO ; Guan-hua DU ; Jin-hua WANG
Acta Pharmaceutica Sinica 2023;58(12):3508-3518
Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.
6.Effects of inhaled budesonide on the bronchial-pulmonary pathology and expression of thymic stromal lymphopoietin in lung tissues in asthmatic rats.
Hui LIU ; Jia-Hua PAN ; Wan-Ling LOU ; Jin-Gen HE
Chinese Journal of Contemporary Pediatrics 2010;12(10):816-819
OBJECTIVEThymic stromal lymphopoietin (TSLP) plays an important role in initiating dendritic cell mediated allergic inflammation. This study was designed to examine the effects of inhaled budesonide on TSLP expression in the lung tissues and on the bronchial-pulmonary pathology in asthmatic rats.
METHODSThirty-two female Sprague-Dawley rats were sensitized and challenged with inhaled ovalbumin (OVA) to induce asthma. The asthmatic rats were randomly divided into 2 groups on the 22nd day of OVA challenge: a budesonide treatment group that received inhaled budesonide at 0.32 mg/kg daily for 7 days and an asthma control group that received inhaled 0.9% normal saline for 7 days. TSLP expression in the lung tissues was measured by Western blot and fluorescent-immunohistochemistry 29 and 36 days after OVA challenge. Bronchial-pulmonary pathological changes were evaluated by hematoxylin & eosin and periodic acid-schiff staining.
RESULTSBudesonide treatment alleviated airway inflammation when compared with the asthma control group 29 days after OVA challenge. However, the airway inflammatory reactions were aggravated in the budesonide treatment group 36 days after OVA challenge (7 days after budesonide discontinuance). TSLP expression in the lung tissues was significantly lower in the budesonide treatment group than that in the asthma control group both 29 and 36 days after OVA challenge (P<0.05).
CONCLUSIONSInhaled budesonide can inhibit the TSLP expression in the lung tissues and alleviate lung inflammatory reactions in asthmatic rats, but there is end-of-dose failure.
Administration, Inhalation ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Blotting, Western ; Bronchi ; pathology ; Budesonide ; administration & dosage ; Cytokines ; analysis ; Female ; Immunohistochemistry ; Lung ; pathology ; Rats ; Rats, Sprague-Dawley
8.Study on the long-time effect on allitridum and selenium in prevention of digestive system cancers.
Guo-hua ZHENG ; Hao LI ; Wan-teng FAN ; Hui-qing LI
Chinese Journal of Epidemiology 2005;26(2):110-112
OBJECTIVETo evaluate the long-time effect on allitridum and selenium in preventing cancer of digestive system.
METHODSPersons who were recruited into the intervention group and took allitridum and selenium to prevent gastric cancer in Qixia county of China from 1989-1991 were followed up to 2001 and data of deaths was collected. The long effect on allitridum and selenium in preventing cancer of digestive system was analysed.
RESULTSData were compared to placebo group five years (1992-1996) after the termination of intervention to have found that the accumulative mortality rate of all cancer, digestive system cancer and gastric cancer had decreased 45.5%, 41.2% and 63.3% in the intervention group respectively. By stratum analysis, accumulative mortality rate of all cancer, digestive system cancer and gastric cancer had decreased 51.5%, 51.5% and 67.7% in males of the intervention group, respectively. Relative risks for males in the intervention group were 0.48, 0.47 and 0.30 times more than the placebo group, respectively. All of them were statistically significant. Relative risks for females in the intervention group were 0.74, 0.92 and 0.70 times more than placebo group. Six to ten years later after the termination of intervention, the accumulative mortality rate and relative risk of all cancers in two groups became similar.
CONCLUSIONAllitridum and selenium had the effect of decreasing the incidence risk of digestive cancer with a protective rate more than 50% for five years after the termination of intervention program.
Adult ; Aged ; Allyl Compounds ; therapeutic use ; Antioxidants ; therapeutic use ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; prevention & control ; Humans ; Male ; Middle Aged ; Selenium ; therapeutic use ; Stomach Neoplasms ; prevention & control ; Sulfides ; therapeutic use
9.Purification and functional characterization of enterohemorrhagic Escherichia coli O157: H7 Shiga toxinⅡ
Yongjun JIAO ; Xiaoyan ZENG ; Xiling GUO ; Hua WANG ; Lunbiao CUI ; Xian LI ; Zhenqing FENG ; Hui SUN ; Jiayi WAN ; Zhiyang SHI
Chinese Journal of Infectious Diseases 2008;26(4):217-220
Objective To purify Shiga toxin Ⅱ (STX Ⅱ) of enterohaemorrhagic Escherichia coli (EHEC) O157: H7 by affinity chromatography, and characterize its biological function. Methods The immno-affinity chromatography column was prepared by STX Ⅱ A subunit-specific antibody S1D8 coupling to Sepharose 4B matrix. The purity and specificity of STX Ⅱ molecule secreted by EHEC O157:H7 were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot, respectively. The purified toxin was serially diluted and the toxic activities to Vero cell line and mice were observed. The 50% cytotoxic dose (CD50) for Vero cell line and 100% lethal dose (LD100) for mice were calculated. The protection effect of anti-STX Ⅱ polysera to the mice against the purified toxin challenge was also observed. Results STX Ⅱ was successfully purified from culture supernatant of EHEC O157:H7 using affinity chromatography scheme. The relative molecular weights of STX Ⅱ A and B subunits were 32 000 and 7 500 confirmed by SDS-PAGE, respectively. The purified toxin could react with monoclonal antibodies against STX Ⅱ A and B subunits, respectively.The toxin was cytotoxic to Vero cell with CD50 of 20 ng/L and lethal to mice with LD100 of 5 ng.The toxin could be neutralized by anti-STX Ⅱ polysera in vivo. Conclusion STX Ⅱ is successfully purified and its toxic effects are confirmed in both cell line and mouse model.
10.Comparative study on bacterial species in conjunctival sac between Qiang minority and Han nationality
Wan-jiang, DONG ; Yue, ZHANG ; Zhi-rong, LIU ; Hui, CHEN ; Kui, CAO ; Hua, YU ; Guang-jin, WANG ; Yu-chan, LI
Chinese Journal of Experimental Ophthalmology 2011;29(2):165-168
Background Qiang minority is minority groups of China with the special habits and customs and living condition. So whether the spectrum of disease and bacteria spectrum in conjunctiva are similar with Han nationality is worth paying attention. Objective Present survey was to obtain the data about bacterial species in conjunctival sac in Qiang minority population with the age 40 years old and more and the compare with matched Han nationality population. Methods This survey study was performed as the standardized training and protocol. A total of 212 eyes of 106 individuals from Qiang minority in Beichuan county and 640 eyes of 320 subjects from Han nationality in Mianyang city received questionnaire survey and ophthalmological examination. The secretion of the inferior palpebral conjunctival sac was embrocated and inoculated on blood plate for 48-72 hours. The bacteria was separated and identified. This study was approved by the Ethic Committee of Sichuan Provicial People' s Hospital. Orally informed consent was obtained before the medical procedure. Results All the examinee finished the survey and examination with a good compliance. No significant difference was found in the demography between these two groups of population. The multiple bacterial positive rate in conjunctival sac was 59. 4% in Qiang minority and that of Han people was 66. 3% with a considerably difference between them (χ2 = 2. 27,P = 0. 13). The multiple bacterial species were simultaneously detected in 26.2% in Qiang minority population and 11.88% Han people, showing evidently difference (χ2 = 106. 40, P = 0. 00 ) . The positive rate of corynbaccterium in conjunctival sac of Qiang minority was statistically lower than that of Han people (20. 7% versus 45. 0% ,χ2 =31. 75 ,P = 0. 00) ,but there was no statistical difference in the positive rate of staphylococcus epidemics between two groups (χ2 = 1. 89 ,P = 0. 17). Conclusion The bacteria positive rate in conjunctiva sac is resemble in the population over 40 years in both the Qiang minority and Han nationality. The simple bacterial species is found in majority people in two groups of subjects. The positive rate of multiple bacterial strains coexistence is more in the Qiang minority. The bacterial strains is different between Qiang minority and Han nationality.