1.Research advances in drug transporters and multidrug resistance
China Oncology 2000;0(06):-
Multidrug resistance (MDR) is the most common cause in the failure of cancer chemotherapy. Drug transporters play an important role in multidrug resistance in cancer. Activation of drug pumps which belong to ATP-binding cassette (ABC) transporters leads to the efflux of drug via cell membrane.Three subgroups of ABC transporters are involved in the transport of cytotoxic drugs.These transporters include ABCB subgroup,ABCC subgroup and ABCG subgroup. In this review,the author discussed the recent research advances in the ABC transporters associated with MDR.
2.Targeted therapies in the treatment of gastric cancer
China Oncology 1998;0(01):-
Gastric cancer is one of the most common malignancies in the digestive system.Most of the patients with gastric cancer have advanced disease at the time of diagnosis.Chemotherapy is still the mainstay of treatment for advanced gastric cancer,but efficacy of chemotherapy was modest.Molecular targeted therapies have emerged as a novel approach to the treatment of both hematological and solid tumors in recent years.The understanding of molecular biological mechanisms underlying the formation,progression and metastasis in advanced gastric cancer has enabled us to use the new approach to treat this disease in clinical practice.These therapeutic strategies include targeting EGFR signal transduction pathway,anti-angiogenesis,targeting NF-?B signal transduction pathway and cyclin-dependent kinase inhibitors.In this review,a brief introduction of the current status of the molecular targeted therapies in the treatment of gastric cancer was presented.Bevacizumab,anti-VEGF monoclonal antibody targeting the angiogenesis pathway has been approved for the treatment of colorectal cancer by FDA,has been reported to show effectiveness in metastatic gastric cancer when combined with cytotoxic agents.Inhibition of NF-?B signal transduction pathway such as PS-341(proteasome inhibitor,bortezomib) approved for the treatment of refractory or recurrent multiple myeloma by FDA has also been used to combine with chemotherapy for gastric cancer.There are also encouraging reports on the combination of standard chemotherapy with Cetuximab,Matuzumab,Gefitinib,Erlotinib and Trastuzumab which target the EGFR and HER2 signal transduction pathways.Flavopiridol is a cyclin-dependent kinase inhibitor with low molecullar weight that aims at the regulatory process of the cell cycle but this needs further clinical trial.
3.Application of case based learning assisted bilingual teaching in hepatobiliary surgery clinical practice
Zhiyu CHEN ; Geng CHEN ; Shuguang WANG
Chinese Journal of Medical Education Research 2015;(3):306-308
We introduced Case based learning into traditional bilingual teaching, dividing the hepatobiliary surgery teaching into four phases: preview, introduction, group discussion and estimation after class . Through the classroom organization analysis of common cases of liver and gallbladder surgery, we took students as the main body, teacher as the guide, to complete the bilingual teaching. Auxiliary case based learning used in bilingual teaching of liver and gallbladder surgery practice is beneficial to improving the quality of bilingual teaching, and helps to cultivate the students' clinical thinking. However, there are still some deficiencies of the case aided bilingual teaching, which needs continuous improvement.
4.Targeted therapy and its application on gastrointestinal stromal tumor
Yingqiang SHI ; Kai HUANG ; Zhiyu CHEN
China Oncology 2009;19(6):409-411
Targeted therapy has gradually become the focus in the treatment of tumor, with the emerge of more and more targeted drugs which has brought the treatment of tumor into a new era. Imatinib, the tyrosine kinase inhibitor, is one of the important types of targeted therapy, has become the standard of care in adjuvant therapy of gastrointestinal stromal tumor(GIST) with extraordinary effects. However, the questions are still on debate incluing the optimal way to evaluate treatment results, the treatment duration, whether it can be intermitted or not, second line therapy for imatinib-intolerance or -resistance and the combination with surgery.
5.Clinical effects of different surgical methods on papillary carcinoma of the thyroid with clinically negative lymph nodes
Xin GUO ; Zhiyu WU ; Chunyou CHEN
Chinese Journal of Clinical Oncology 2016;43(9):366-370
Objective:To explore the efficacy and safety of different surgical methods in papillary thyroid carcinoma (PTC) patients with negative cervical lymph nodes (cN0) and to provide theoretical basis for the selection of surgical procedures. Methods:A total of 225 PTC cN0 patients were selected and divided into two groups according to the operation method. Only 110 patients underwent total thy-roidectomy, whereas the 115 cases in the lobectomy group underwent ipsilateral lobectomy and isthmus resection. Al patients were treated with ipsilateral central lymph node dissection. We analyzed both groups of patients in terms of surgery, hospitalization, pathological characteristics, complications, follow-up, and recurrence. Results:(1) The length of incision, blood loss, operation time, and length of stay were not significantly different between the two groups (P>0.05). (2) In the total resection group, the number of multiple foci of the cancer cases was significantly more than that of the lobectomy patients (P<0.05). The average tumor diameter in both groups were not significantly different (P>0.05). Between the two groups, the number of central lymph node dissection and total lymph node metastasis, and the number of cases with central lymph node metastasis were not significantly different (P>0.05). Likewise, the incidence rates of mistakenly cut parathyroid, extremely low blood calcium levels, temporary larynx return nerve paralysis, and superior laryngeal nerve injury were not significantly different between the two groups (P>0.05). No permanent hypocalcemia or permanent recurrent laryngeal nerve injury occurred. (3) All patients were followed up for 2-4.5 years. No recurrent cases were reported in the total resection group. For the lobectomy group, 8 patients with adenocarcinoma had contralateral tumor metastasis and underwent contralateral lobe resection, whereas 4 patients suffered from ipsilateral neck lymph node metastasis at the side area and underwent functional lymph node clearance. Significant differences were noted in the metastasis and recurrence rates between the two groups of patients (P<0.05). No deaths were reported during the follow-up period. Conclusion:For PTC cN0 patients, total thyroidectomy with joint ipsilateral central lymph node clearance can reduce the residual tumor, metastasis, and risk of recurrence,compared with surgery limited to the affected lobe and isthmus. Postoperative complications were not significantly increased.
7.Effects of 3 carbohydrates on CAP10 promoter activity of Cryptococcus neoformans capsule-associated gene
Zhiyu ZHAO ; Hai WEN ; Sunxiao CHEN
Academic Journal of Second Military Medical University 1982;0(02):-
Objective:To study the effects of glucose,mannose and galactose on CAP10 promoter activity of Cryptococcus neoformans capsule-associated gene.Methods: Yeast cells were transfected with plasmid containing a 951 bp length of 5′ upstream flanking sequence of CAP10 coding region and a reporter gene,chloramphenicol acetyl transferase(CAT);the transfectants were treated with different concentrations(10,20,40,60,80 mg/ml) of glucose,mannose and galactose.CAT activity was assessed by ELISA method and CAT activities of different groups were compared.Results: Different concentrations of glucose and mannose had no obvious influence on CAT activity;different concentrations of galactose had obvious influence on CAT activity and the influence was positively dependent with its dose within the experimental concentration range.Conclusion: Glucose and mannose have no obvious effect on the activity of CAP10 promoter;galactose has obvious inductive effect on activity of CAP10 promoter,suggesting that CAP10 gene might be related with galactose metabolism.
8.Effect of Danhong Zhiganching capsules in rats with experimental fatty liver
Yuan LIU ; Zhen CHEN ; Zhiyu QIAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2004;0(07):-
AIM:To study the effect of Danhong Zhiganching capsules on the experimental fatty liver in rats.METHODS: Male SD rats were treated by high fat diet for 6-week after being treated by a low dose of CCl_4 to induce fatty liver model.Then,drugs were given by oral to the rats,the contents of triglyeride,total cholesterol in serum and liver tissue,the contents of superoxide dismutase and malondialdehyde in serum and the contents of free fatty acids in liver tissue acted as indexes to determine the effect of Danhong Zhiganching capsules.RESULTS: The contents of triglyeride and total cholesterol in serum and liver tissue of rats were significantly reduced by Danhong Zhiganching capsules,and so it is with the contents of free fatty acids in liver tissue(P
9.Analysis of HIV infection and its epidemic characteristics among pregnant women in Hunan from 2011 to 2015
Aihua WANG ; Zhiyu LIU ; Lizhang CHEN
Journal of Chinese Physician 2016;18(12):1816-1819
Objective To investigate the prevalence of human immunodeficiency virus (HIV) infection and its characteristics among pregnant women in Hunan.Methods Data from information system of prevention of mother-to-child transmission of HIV management in Hunan 2011-2015 was analyzed in the study (3 + 1 mode by year statistics).Results The total HIV-positive infection rate was 0.19‰ among pregnant women from 2011 to 2015 in Hunan.The rate of HIV infection showed upward trend by years (P < 0.05).The proportion of diagnosis of HIV positive cases intrapartum was 44.66%,showed declining trend by years (P < 0.05).The 786 cases of HIV positive pregnant women were mainly the Han's,the age distribution of 20 to 35 years old,90.21% of them were farmers or unemployed.A percentage (76.84%) of them had junior high school education level or lower 37.91% of them were found in delivery or postpartum.A percentage (36.51%) of them accepted service in delivery or postpartum.A percentage (45.67%) of them was infected through sexual contact,46.82% of them were infected by unknown ways.Conclusions The rate of HIV infection among pregnant women was increased by years in Hunan.It is suggested to strengthen health education among high-risk groups and high incidence areas,improve detection rate of early pregnant women,implement the Prevention of Mother to Child Transmission (PMTCT) measures to reduce the rate of mother to child transmission of Acquired Immune Deficiency Syndrome (AIDS).
10.Mechanisms of tumor necrosis factor-related apoptosis inducing ligandcombined with Triptolide in inducing the apoptosis of pancreatic cancer cells
Yan JIANG ; Wei LIU ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2015;14(4):321-328
Objective To investigate the mechanisms of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) combined with Triptolide in inducing the apoptosis of pancreatic cancer cells.Methods (1) The pancreatic cancer cells (MiaPaca-2 cells) were divided into 4 groups:blank control group (no drugs were added),TRAIL + Triptolide-group (only TRAIL was added),TRAIL-Triptolide + group (only Triptolide was added) and TRAIL+ Triptolide+ group (TRAIL and Triptolide were added).The vitality of cells in all the 4 groups was assessed by CCK-8.The expressions of poly ADP-ribose polymerase (PARP),cysteinyl aspartate specific proteinase-3 (Caspase-3) and Caspase-8 were detected by Western blot.The vitality of cells was detected by CCK-8 and the vitality of Caspase-8 was detected by Caspase-Glo assays after adding Z-IETD-FMK,a specific inhibitor of Caspase-8.The expressions of myeloid cell leukemia-1 (Mcl-1),Bcl-xL and Bcl-2 were detected by Western blot.(2) The MiaPaca-2 cells were divided into 8 groups:①TRAIL-Mcl-1 siRNA-group (no TRAIL was added and Mcl-1 siRNA cells were not transfected),TRAIL+ Mcl-1 siRNA-group (TRAIL was added and Mcl-1 siRNA cells were not transfected),TRAIL-Mcl-1 siRNA + group (TRAIL was not added and Mcl-1 siRNA cells were transfected)and TRAIL+ Mcl-1 siRNA+ group (TRAIL was added and Mcl-1 siRNA cells were transfected).②TRAIL-Bcl-xL siRNA-group (TRAIL was not added and Bcl-xL siRNA was not transfected),TRAIL+ Bcl-xL siRNA-group (TRAIL was added and Bcl-xL siRNA was not transfected),TRAIL-Bcl-xL siRNA + group (TRAIL was not added and Bcl-xL siRNA was transfected) and TRAIL+ Bcl-xL siRNA+ group (TRAIL was added and Bcl-xL siRNA was transfected).The vitality of the cells in all the groups was detected by CCK-8.The expressions of Caspase-3 and Caspase-8 protein were detected by Western blot.The measurement data with normal distribution were presented as (x) ± s.The comparison among groups was done by ANOVA,and the pairwise comparison was done by LSD-t test.Results (1) The vitalities of MiaPaca-2 cells in the blank control group,TRAIL + Triptolide-group,TRAIL-Triptolide + group and TRAIL + Triptolide + group were 100.0% ± 1.1%,81.2% ± 2.3%,78.6% ± 3.6%and 40.1% ± 2.5 %,and the relative expressions of PARP protein were 0.510 ± 0.028,0.720 ±0.072,1.250 ±0.023 and 2.560 ± 0.220,the relative expressions of Caspase-3 were 0.080 ± 0.004,0.080 ± 0.003,0.110 ±0.005 and 2.720 ± 0.003,and the relative expressions of Caspase-8 were 0.070 ± 0.003,0.080 ± 0.005,0.120 ±0.003 and 0.990 ± 0.006,with significant differences among the 4 groups (F =203.607,1 457.785,332 421.900,35 437.218,P < 0.05).The vitality of M iaPaca-2 cells in the TRAIL + Triptolide + group was significantly different from those in the blank control group,the TRAIL + Triptolide-group and the TRAIL-Triptolide + group (t =34.583,355.936,36.271,P < 0.05).The relative expression of PARP protein of MiaPaca-2 cells in the TRAIL+ Triptolide + group was significantly different from those in the blank control group,TRAIL+ Triptolidegroup and TRAIL-Triptolide + group (t =591.784,63.739,2 268.987,P < 0.05).The relative expression of Caspase-3 protein of the MiaPaca-2 cells in the TRAIL + Triptolide + group was significantly different from those in the blank control group,the TRAIL + Triptolide-group and theTRAIL-Triptolide + group (t =3 266.153,9 145.228,1 738.713,P <0.05).The relative expression of Caspase-8 protein of the MiaPaca-2 cells in the TRAIL+ Triptolide +group was significantly different from those in the blank control group,the TRAIL+ Triptolide-group and the TRAIL-Triptolide + group (t =663.953,l 432.878,327.584,P < 0.05).The vitality of caspase-8 in the TRAIL+ Triptolide+ group was 711.0% ± 5.1% before adding Z-IETD-FMK,and then the vitality of MiaPaca-2 cells and caspase-8 changed to 70.0% ± 4.8% and 73.0% ± 2.4%,with significant differences (t =17.956,55.027,P < 0.05).The relative expressions of Mcl-1 protein in the blank control group,the TRAIL + Triptolidegroup,the TRAIL Triptolide + group and the TRAIL + Triptolide + group were 1.68 ± 0.22,2.08 ± 0.11,0.73 ±0.15 and 0.58 ± 0.18,the relative expressions of Bcl-xL protein were 0.65 ± 0.03,0.47 ± 0.03,0.32 ± 0.03and 0.26 ±0.05,the relative expressions of Bcl-2 protein were 0.65 ± 0.03,0.67 ± 0.03,0.62 ± 0.05 and 0.67 ± 0.03,with significant difference among the 4 groups (F =55.178,88.683,3.411,P < 0.05).The relative expressions of Mcl-1 protein of the MiaPaca-2 cells in the TRAIL-Triptolide + group and the TRAIL+ Triptolide +group were significantly different from those of the blank control group (t =23.506,47.631,P < 0.05) and the TRAIL + Triptolide-group (t =58.457,37.115,P < 0.05).The relative expressions of Bcl-xL protein of the MiaPaca-2 cells in the TRAIL-Triptolide + group and the TRAIL + Triptolide + group were significantly different from those of the blank control group (t =38.105,42.219,P < 0.05) and the TRAIL + Triptolide-group (t =32.476,15.814,P < 0.05).The relative expressions of Bcl-2 protein in the TRAIL-Triptolide + group and the TRAIL+ Triptolide + group were not significantly different from those of the blank control group (t =4.724,1.732,P > 0.05) and the TRAIL + Triptolide-group (t =3.464,0.000,P > 0.05).(2) The vitalities of MiaPaca-2 cells of the TRAIL-Mcl-1 siRNA-group,TRAIL + Mcl-1 siRNA-group,the TRAIL-Mcl-1 siRNA + group and the TRAIL + Mcl-1 siRNA + group were 100.0% ± 2.2%,79.3% ± 1.8%,71.2% ± 3.2% and 37.3% ± 5.4%,the relative expressions of Caspase-8 protein were 0.100 ± 0.003,0.100 ± 0.005,0.100 ± 0.003 and 0.350 ±0.005,and the relative expressions of Caspase-3 protein were 0.020 ± 0.003,0.060 ± 0.003,0.020 ± 0.003 and 0.590 ±0.004,with significant differences among the 4 groups (F =136.681,2 717.391,44 471.429,P <0.05).The vitality of MiaPaca-2 cells of the TRAIL + Mcl-1 siRNA + group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =33.937,20.207,26.689,P < 0.05).The relative expression of Caspase-8 protein of the TRAIL + Mcl-1 siRNA +group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =216.506,433.013,144.338,P < 0.05).The relative expression of Caspase-3 protein of the TRAIL + Mcl-1 siRNA + group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =329.09,458.993,987.269,P <0.05).The vitalities of MiaPaca-2 cells of the TRAIL-Bcl-xL siRNA-group,the TRAIL+ Bcl-xL siRNA-group,the TRAIL-Bcl-xL siRNA + group and the TRAIL+ Bcl-xL siRNA + group were 100.0% ± 2.3%,87.2% ± 4.1%,74.1 ± 3.7% and 56.3% ± 5.4%,and the relative expressions of Caspase-3 protein were 0.060 ±0.004,0.070 ± 0.003,0.060 ± 0.004 and 0.390 ± 0.003,with significant differences among the 4 groups (F =70.074,4 643.478,P < 0.05).The vitality of MiaPaca-2 cells of the TRAIL + Bcl-xL siRNA + group was significantly different from those in the TRAIL-Bcl-xL siRNA-group,the TRAIL+ Bcl-xL siRNA-group and the TRAIL-Bcl-xL siRNA + group (t =24.416,41.170,18.136,P < 0.05).The relative expression of Caspase-3 protein of the TRAIL + Bcl-xL siRNA + group was significantly different from those in the TRAIL-Mcl-1 siRNA-group,the TRAIL + Mcl-1 siRNA-group and the TRAIL-Mcl-1 siRNA + group (t =285.788,554.256,190.526,P < 0.05).Conclusion Triptolide could induce the apoptosis of MiaPaca-2 cells by inhibiting the expressions of Mcl-1 and Bcl-xL,sensitizing TRAIL and activating Caspase-8 and Caspase-3.