Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: ...Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.展开更多
Objective: The purpose of the present study is to detect characteristics of primary expression of mdr 1 gene in several neoplasms which has high morbidity in clinic. Methods: 151 resected samples, which are patholog...Objective: The purpose of the present study is to detect characteristics of primary expression of mdr 1 gene in several neoplasms which has high morbidity in clinic. Methods: 151 resected samples, which are pathologically malignant and clinically untreated before operation, were obtained from Anyang Cancer Hospital. All of them were investigated with RT PCR for the expression of mdr 1 gene and correlated each other. Besides, we evaluated the advantages of RT PCR in this study. Results: The mdr 1 gene expression rate of these 151 samples, including cancers of stomach and gastric cardia (n=51), esophagus (n=46), colorectum (n=16), breast (n=15), thyroid (n=10), lung (n=9), uterine cervix (n=4), was 33.3%, 37%, 31.3%, 13.2%, 40%, 55%, 0%, respectively. Conclusion: Compared with other methods, RT PCR for studying mdr 1 gene expression had certain advantages in simplicity, reliability, and accuracy. Overexpression of mdr 1 gene in these neoplasms suggested that cases should be distinguished before treatment according to MDR of tumor and to choose effective drugs for individual cancer patient.展开更多
Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric phy...Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.展开更多
INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relatio...INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].展开更多
The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected ...The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.展开更多
Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the correspondi...Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 mg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.展开更多
Objective： To explore the effects and mechanism of glycogen synthase kinase 3β （GSK-313） inhibitor （2＇Z,3＇E）-6-bromo-indirubin-3＇-oxime （BIO） on drug resistance in colon cancer cells. Methods： The colon c...Objective： To explore the effects and mechanism of glycogen synthase kinase 3β （GSK-313） inhibitor （2＇Z,3＇E）-6-bromo-indirubin-3＇-oxime （BIO） on drug resistance in colon cancer cells. Methods： The colon cancer SW480 and SW620 cells were treated with BIO, 5-fluorouracil （5-FU） and BIO/5-FU, separately. Cell cycle distribution, apoptosis level and efflux ability of rhodamine 123 （Rh123） were detected by flow cytometry. The protein expressions of P-glycoprotein （P-gp）, multidrug resistance protein 2 （MRP2）, thymidylate synthase （TS）, β-catenin, E2F-1 and βcl-2 were detected by Western blot. β-catenin and P-gp were stained with double immunofluorescence and observed under a confocal microscope. Results： BIO up-regulated β-catenin, P-gp, MRP2 and TS, enhanced the efflux ability of Rh123, decreased Bcl-2 protein and gave the opposite effect to E2F-1 protein in SW480 and SW620 ceils. Furthermore, BIO significantly inhibited cell apoptosis, increased S and G2/M phase cells, and reduced the cell apoptosis induced by 5-FU in SW480 cells, whereas the effects were slight or not obvious in SW620 cells. Conclusion： GSK-3β was involved in drug resistance regulation, and activation of β-catenin and inhibition of E2F-1 may be the most responsible for the enhancement of 5-FU chemotherapy resistance induced by GSK-β inhibitor β10 in colon cancer.展开更多
文摘Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.
文摘Objective: The purpose of the present study is to detect characteristics of primary expression of mdr 1 gene in several neoplasms which has high morbidity in clinic. Methods: 151 resected samples, which are pathologically malignant and clinically untreated before operation, were obtained from Anyang Cancer Hospital. All of them were investigated with RT PCR for the expression of mdr 1 gene and correlated each other. Besides, we evaluated the advantages of RT PCR in this study. Results: The mdr 1 gene expression rate of these 151 samples, including cancers of stomach and gastric cardia (n=51), esophagus (n=46), colorectum (n=16), breast (n=15), thyroid (n=10), lung (n=9), uterine cervix (n=4), was 33.3%, 37%, 31.3%, 13.2%, 40%, 55%, 0%, respectively. Conclusion: Compared with other methods, RT PCR for studying mdr 1 gene expression had certain advantages in simplicity, reliability, and accuracy. Overexpression of mdr 1 gene in these neoplasms suggested that cases should be distinguished before treatment according to MDR of tumor and to choose effective drugs for individual cancer patient.
基金Supported by Chinese Medicine Service System and Capacity Building(Key Project with Chinese Medicine Characteristics and Advantages,Ruikang Hospital,2023)Guangxi Science and Technology Major Project during the 14th five-year Plan,No.Guike AA22096028.
文摘Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.
基金Supported in part by phone-Poulenc Rorer Pharmaceuticals INC
文摘INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].
文摘The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug associated protein (MRP), P glycoprotein (P gp), P53 and Bcl 2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P gp, P53 and Bcl 2 was 52.5 %, 57.5 %, 47.5 % and 62.5 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in the grade Ⅰ, Ⅱ and Ⅲ of tumors was 46.3 %, 38.5 %, 38.5 %, 23.1 %; 52.9 %, 39.8 %, 47.1 %, 76.4 %; 60.0 %, 80.0 %, 60.0 %, 90.0 % respectively. The positive rate of MRP, P gp, P53 and Bcl 2 in 24 primary tumor specimens was 37.5 %, 41.7 %, 33.3 %, 45.8 % and that in 16 cases in recurrent specimens receiving chemotherapy 75.0 %, 81.3 %, 68.8 %, 87.5 % respectively. It was suggested the positive rate of MRP, P gp, P53 and Bcl 2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased ( P <0.05). The expression of MRP, P gp, P53 and Bcl 2 proteins might be the important factors for chemotherapy failure.
文摘Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 mg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.
基金supported by the Sci-Tech Project Foundation of Guangdong Province(No.2009B080800023)
文摘Objective： To explore the effects and mechanism of glycogen synthase kinase 3β （GSK-313） inhibitor （2＇Z,3＇E）-6-bromo-indirubin-3＇-oxime （BIO） on drug resistance in colon cancer cells. Methods： The colon cancer SW480 and SW620 cells were treated with BIO, 5-fluorouracil （5-FU） and BIO/5-FU, separately. Cell cycle distribution, apoptosis level and efflux ability of rhodamine 123 （Rh123） were detected by flow cytometry. The protein expressions of P-glycoprotein （P-gp）, multidrug resistance protein 2 （MRP2）, thymidylate synthase （TS）, β-catenin, E2F-1 and βcl-2 were detected by Western blot. β-catenin and P-gp were stained with double immunofluorescence and observed under a confocal microscope. Results： BIO up-regulated β-catenin, P-gp, MRP2 and TS, enhanced the efflux ability of Rh123, decreased Bcl-2 protein and gave the opposite effect to E2F-1 protein in SW480 and SW620 ceils. Furthermore, BIO significantly inhibited cell apoptosis, increased S and G2/M phase cells, and reduced the cell apoptosis induced by 5-FU in SW480 cells, whereas the effects were slight or not obvious in SW620 cells. Conclusion： GSK-3β was involved in drug resistance regulation, and activation of β-catenin and inhibition of E2F-1 may be the most responsible for the enhancement of 5-FU chemotherapy resistance induced by GSK-β inhibitor β10 in colon cancer.
