Study progression on mechanism of long non-coding RNAs regulating drug resistance in osteosarcoma / 国际肿瘤学杂志

Osteosarcoma is the most common primary solid bone malignancy. The main factor leading to recurrence and metastasis of osteosarcoma is resistance to chemotherapy drugs. Long non-coding RNAs can affect drug resistance in osteosarcoma by regulating epithelial-mesenchymal transition, cell autophagy, apoptosis, drug efflux, and cell cycle, suggesting that long non-coding RNAs may become new targets for drug resistance in osteosarcoma treatment.

Metformin improves oxaliplatin resistance in colorectal cancer cells by inhibiting EIF3G expression / 中华普通外科杂志

Objective To analyze the mechanism of metformin in improving oxaliplatin resistance of colorectal cancer cells.Methods The expression levels of EIF3G in 71 cases of colorectal cancer and adjacent tissues were detected by RT-qPCR.The survival curve was established by Kaplan-Meier method.The survival rate difference between the two groups was compared by Log-rank test.HCT-116 cells were infected with shEIF3G lentivirus,HCT-116 L-OHP-resistant cell line was constructed.After treated with metformin,sensitivity to L-OHP was detected by CCK-8 assay,RT-qPCR and Western blot were used to analyze the EIF3G mRNA and protein levels.The subcutaneous tumor model of nude mice was constructed to observe the effect of metformin on tumor growth.Results The expression level of EIF3G mRNA in colorectal cancer tissues was up-regulated by (3.24 ± 0.43) times compared with paraneoplastic tissues (P ＜ 0.01).EIF3G level was significantly correlated with the prognosis of colon cancer patients.Knockdown EIF3G could enhance the L-OHP sensitivity of HCT116/L-OHP cells (P ＜ 0.05);Metformin can reduce the expression level of EIF3G and improve the drug resistance of HCT116/L-OHP cells (P ＜ 0.05),and inhibit the development of colorectal cancer in vivo (P ＜ 0.05).Conclusion Metformin can inhibit the expression of EIF3G and improve the L-OHP resistance of HCT-116 cells.

Metformin improves oxaliplatin resistance in colorectal cancer cells by inhibiting EIF3G expression / 中华普通外科杂志

Objective@#To analyze the mechanism of metformin in improving oxaliplatin resistance of colorectal cancer cells.@*Methods@#The expression levels of EIF3G in 71 cases of colorectal cancer and adjacent tissues were detected by RT-qPCR. The survival curve was established by Kaplan-Meier method. The survival rate difference between the two groups was compared by Log-rank test.HCT-116 cells were infected with shEIF3G lentivirus, HCT-116 L-OHP-resistant cell line was constructed.After treated with metformin, sensitivity to L-OHP was detected by CCK-8 assay, RT-qPCR and Western blot were used to analyze the EIF3G mRNA and protein levels. The subcutaneous tumor model of nude mice was constructed to observe the effect of metformin on tumor growth.@*Results@#The expression level of EIF3G mRNA in colorectal cancer tissues was up-regulated by (3.24±0.43) times compared with paraneoplastic tissues (P<0.01). EIF3G level was significantly correlated with the prognosis of colon cancer patients. Knockdown EIF3G could enhance the L-OHP sensitivity of HCT116/L-OHP cells (P<0.05); Metformin can reduce the expression level of EIF3G and improve the drug resistance of HCT116/L-OHP cells (P<0.05), and inhibit the development of colorectal cancer in vivo (P<0.05).@*Conclusion@#Metformin can inhibit the expression of EIF3G and improve the L-OHP resistance of HCT-116 cells.

Efficacy and safety of vandetanib on advanced medullary thyroid carcinoma: single center result from a phase Ⅲ study / 中华耳鼻咽喉头颈外科杂志

Objective@#There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib,a novel multitargeted receptor tyrosine kinase inhibitor, has previously shown antitumor activity in phase Ⅱ studies of patients with advanced MTC. This study was to evaluate the efficacy and the safety of vandetanib on advanced MTC.@*Methods@#This study was an open, international multi-center phase Ⅲ clinical trial and the study number was NCT01298323. The single-center study was a sub-group analysis of the international study, which was conducted on 9 pathologically confirmed advanced MTC patients by Cancer Hospital Chinese Academy of Medical Sciences between March 2012 and October 2017. Vandetanib (300 mg) was orally administered daily till death or withdrawal. The efficacy was evaluated according to RECIST criteria and the adverse events were evaluated according to NCI criteria.@*Results@#The objective response rate was 3/9,and the disease control rate was 4/9. The median progression-free survival was 44 months. All patients who had the elevated levels of calcitonin (CTN) and carcino-embryonic antigen (CEA) before treatment began to show the decreases in the level of CTN and CEA after 3 months and later showed again the increases in the levels of both tumor markers with tumor progression. By ROC curve analysis, CTN was of statistically significance(P<0.05, 95%CI 0.558-0.834), but CEA was not(P>0.05). Adverse events were generally mild (grade 1 or 2),including hypertension (9 cases),skin rash (9 cases), and diarrhea (6 cases). Two patients developed grade 3 elevation of serum glutamate pyruvate transaminase and one patient developed grade 3 elevation of drug-related bowel disease. No grade 4 drug-related adverse event occurred.@*Conclusions@#Vandetanib is effective and well tolerated for patients with locally advanced or metastatic MTC who have no chance for surgery. This indicates the increase of CTN is clinically relevant to disease progression, but the number of patients are extremely low, and, therefore further research is needed. Long-term use of vandetanib may cause resistance.

Expression of CD44v6 in colorectal cancer and its impact on chemosensitivity: Progression in research / 国际外科学杂志

Colorectal cancer is one of the most common malignant tumors,early diagnosis and treatment are the important factors affecting colorectal cancer's prognosis.It has been proved that colorectal cancer's diagnosis combined with biomolecular markers is non-invasive,economical and specific at the same time,biomarkers are valuable in predicting and monitoring the chemoresistance of colorectal cancer.This article mainly reviews the prediction of liver metastasis of colorectal cancer,drug resistance of postoperative chemotherapy in colorectal cancer and the monitoring of drug resistance in the course of chemotherapy by CD44v6.

Progress on resistance to new endocrine therapy in castration-resistant prostate cancer / 肿瘤

Prostate cancer (PCa) is the most common tumor in Europe and America. In recent years, the incidence rate of PCa has been increased in China. Castration-resistant prostate cancer (CRPC) is a serious difficulty in treatment of prostate cancer. The androgen receptor (AR) signal axis still plays an important role in the survival and progression of the tumor when PCa turns into CRPC. The new endocrine therapy is characterized by targeting AR signal axis, in which Abiraterone and Enzalutamide are the representatives. These two drugs can effectively inhibit the activity of AR signal axis, and prolong the survival of the patients. Although the new endocrine therapy drugs are safe and effective for CRPC, but the subsequent drug resistance can seriously affect the clinical efficacy. This paper reviews the progress on the mechanism of drug resistance of new endocrine therapy in recent years, in order to provide some references for solving the problem of drug resistance and guide the development of new drugs.

MicroRNAs and ovarian cancer / 国际肿瘤学杂志

The abnormal expressions of microRNAs (miRNAs) are closely related to the genesis and development of ovarian cancer.MiRNAs are involved in carcinogenesis and progression,invasion and metastasis as well as drug resistance.As a kind of significant biomarker,miRNAs are expected to be novel targets for the early diagnosis and prognostic evaluation of ovarian cancer,which provide new ways for the therapy of ovarian cancer.

MicroRNAs and ovarian cancer / 国际肿瘤学杂志

The abnormal expressions of microRNAs (miRNAs) are closely related to the genesis and development of ovarian cancer.MiRNAs are involved in carcinogenesis and progression,invasion and metastasis as well as drug resistance.As a kind of significant biomarker,miRNAs are expected to be novel targets for the early diagnosis and prognostic evaluation of ovarian cancer,which provide new ways for the therapy of ovarian cancer.

Resistance mechanisms of tumour-initiating cells / 国际外科学杂志

Tumor initiating cells are the source of the tumor,which have the characteristics of stem cells,such as self-renewal capacity,unlimited proliferation,multi-directional differentiation,DNA repair activity and resistance to apoptosis.The tumor initiating cells involved in chemotherapy drug resistance,traditional chemotherapy drugs is difficult to kill them,studies have shown that the tumor initiating cells involved in chemotherapy drug resistance.Tumor initiating cells are the significant factor of drug resistance and relapse in the tumor.tumor initiating cells resistance mechanism is complex,not only involved in tumor generally resistant characteristics,but kept natural resistance properties of stem cells.Tumor initiating cells resistant mechanism is controversial.This review introduces the resistance mechanisms of tumor-initiating cells both in tumor initiating cells-intrinsic and tumor initiating cells-extrinsic aspects based on the domestic and international relevant literatures.By revealing the drug resistance mechanism,it can be used to predict the effect of clinical chemotherapy,and now the article will review the research progress of the drug resistance mechanism of tumor initiating cells.

Construction of colonic cancer drug-resistant cell line COLO and its relationship with tumor stem cells / 国际肿瘤学杂志

Objective To construct a colon cancer chemotherapy-resistant cell line COLO,and study its characteristics and its relationship with tumor stem cells.Methods We constructed two 5-fluorouraci (5-FU)-resistant colon cancer cell line COLO/5-FU-1 and COLO/5-FU-2, which were resistant to 0.1 0 μmol/ml and 0.20 μmol/ml 5-FU respectively through gradiently increased drug concentration.The cha-racteristics of 5-FU-resistant cell lines were compared with parental colon cancer cell line COLO related to proli-feration,colony forming ability,migration and invasion,sphere forming ability,expression of stemness genes and cross drug-resistance.Results In the cell viability assay,4 days after regular training,the absorbancy of colon cancer 5-FU-resistant cell lines COLO/5-FU-2,COLO/5-FU-1 and parental colon cancer cell line COLO were 0.61 ±0.1 3,0.54 ±0.07 and 0.41 ±0.09 respectively,with significant difference (F =63.43,P =0.033).With the increased concentration of 5-FU,5-FU-resistant cell lines presented increasing clonality. The cloning efficiency of COLO/5-FU-2,COLO/5-FU-1 and parental colon cancer cell line COLO were (87.6 ±1 2.7)%,(65.3 ±9.7)% and (38.5 ±7.6)% respectively,with significant difference (F =33.64, P =0.01 7).In each high power field of vision,the cell numbers of migration through the basement membrane of COLO/5-FU-2,COLO/5-FU-1 and parental colon cancer cell line COLO were 482 ±39,434 ±45 and 373 ±38 respectively;and the cell numbers of invasion through the basement membrane were 1 74 ±42,1 1 2 ± 31 and 87 ±29 respectively,with significant differences (F =1 09.61 ,P =0.009;F =67.31 ,P =0.032). Compared with parental colon cancer cell line COLO,5-FU-resistant cell lines had higher expression of stem-ness genes (F =47.31 ,P =0.042).5-FU-resistant cell lines were cross-resistant to other chemotherapeutic drugs such as mitoxantrone.For example,after incubation for 96 hours,inhibition rate of mitoxantrone to parent colon cancer cell line COLO was higher significantly than COLO/5-FU-1 and COLO/5-FU-2 (0.749 ± 0.042,0.423 ±0.024,0.342 ±0.01 8),with significant difference (F =1 2.61 ,P =0.028).The micro-sphere forming rates of COLO/5-FU-2,COLO/5-FU-1 and parental colon cancer cell line COLO were (8.90 ± 0.97)%,(6.20 ±0.75)% and (3.90 ±0.32)% respectively,with significant difference (F =1 64.32,P =0.006).Conclusion Colon cancer drug-resistant cell line COLO possess tumor stem cell-like characteristics, which are enriched in cancer stem cells.

Correlation between promoter methylation of hMLH1 and DAPK genes and drug resistance of lung cancer / 肿瘤研究与临床

Drug resistance is one of the major obstacles for chemotherapy and targeted therapy in lung cancer with complex mechanisms.The researches have demonstrated that epigenetic changes are closely related to drug resistance of tumor.DNA methylation is an important epigenetic modification.In this paper, the relationships between hMLH1 promoter aberrant methylation and platinum-resistance, and DAPK promoter aberrant methylation and EGFR-TKI resistance in lung cancer will be briefly reviewed.

Research progress of phosphatidylinositol 3-kinase/AKt signaling pathway and mechanisms of resistance to sorafenib in hepatocellular carcinoma / 国际外科学杂志

Sorafenib is a molecular targeted drug for the treatment of advanced primary liver cancer.However,along with the occurrence of drug resistance,the therapeutic effect was effected.At present,there is clear evidence that the emergence of drug resistance of live cancer is closely related to the epithelial-mesenchymal transition,liver cancer stem cells and the heterogeneity of liver cancer,and the PI3K/AKt signaling pathway as the vital common signaling channel was involved in the above mentioned process.From this we can conclude that complementary inhibtion of PI3K/AKt signaling pathway at the same time is the method that can strengthen the effect of sorafenib on the treatment of liver cancer so far.

Multidrug resistance genes and related drug resistance proteins in cancer / 国际肿瘤学杂志

Chemotherapy is one of the most important methods of cancer treatment.However,multidrug resistance (MDR) has been the main factors affecting their efficacies.Recent studies show that the amplification of MDR1 gene in tumor cells,the over expression of the related drug resistance protein and the cell cycle and apoptosis pathway in signal transduction are the main causes for the failure of chemotherapy.

Molecular mechanisms of Survivin gene expression regulated by imatinib / 白血病·淋巴瘤

Objective To investigate the influences of imatinib on Survivin gene expression in bcr-abl-transformed leukemia cells.Methods Firstly,PCR and Western blot were carried out to detected Survivin expression with imatinib treatment in 32Dcl3 and 32D-bcr-abl cell lines.Then the luciferase reporter plasmids containing human Survivin promoter as well as its deletion and site-directed mutation were constructed to identify the essential responsive elements for suppressing Survivin promoter activity by imatinib.Chromatin immunoprecipitation was performed to confirm the binding of c-myc to Survivin promoter.10058-F4,a small molecule c-myc inhibitor,was used to disrupt c-myc activity and evaluate its anti-leukemic effect combined with imatinib.Results Both of mRNA and protein level of Survivin in bcr-abl-transformed cells were downregulated upon imatinib treatment.The decrease of Survivin expression was controlled at the transcriptional level through a mechanism in which imatinib repressed survivin promoter activity by disturbing the interaction between c-myc and E-box elements.Interruption of c-myc activity by 10058-F4 exerted an anti-leukemia effect with enhancing the sensibility of K562/G01 cells to imatinib.Conclusion Imatinib down-regulates Survivin expression through c-myc-mediated transcription and interference with c-myc might be a potential utility for treatment of imatinib resistant leukemia.

Research progress of gallbladder carcinoma and neoplastic stem cells / 国际外科学杂志

Gallbladder carcinoma is the most common malignant tumor in biliary system,the early diagnosis rate is still very low and the prognosis is extremely poor.At present,the pathogenesis of gallbladder is not clear.Recently,with the development of the neoplastic stem cell research on gallbladder carcinoma,the latest study showed SP positive cells could be separated from the GBC-SD cell.Further more,related researches have shown that gallbladder respectively with CD133+ cells,CD44+ cells,CD133+ CD44+ cells had possessed the cloned formation ability,the stronger growth ability,the differentiation capacity and forming-tumor ability.In this review,we will discuss the research of the relationship between the gallbladder carcinoma and neoplastic stem cells.

P-glycoprotein expression in lung cancer and progress in cisplatin resistance / 肿瘤研究与临床

Cisplatin is widely used in lung cancer chemotherapy, but drug resistance seriously affects its efficacy.The mechanism of cisplatin resistance is not yet clear.Now it is widely recognized that P-glycoprotein (P-glycoprotein, P-gp) expression is associated with cisplatin resistance. Inhibition of P-gp expression can overcome cisplatin resistance and improve the treatment efficacy.

Research development on drug resistance of taxol and β tubulin Ⅲ / 肿瘤研究与临床

The taxol s effect of inducing apoptosis is mainly related to its ability to promote tubulin polymerization and prevent tubulin chain depolarization. Drug resistance is the main restriction factor for clinical usage of taxol. Some basic and clinical studies support that poor response to taxol and poor prognosis are related to overexpression of β tubulin Ⅲ.

MicroRNA and anticancer drug resistance / 肿瘤研究与临床

MicroRNAs (miRNAs) are a small noncoding family of 22 ut RNAs that play an important role in the negative regulation of gene expression at the post-transcriptional level by base pairing to the 3'untranslated region of target messenger RNAs.miRNAs are involved in a variety of basic processes,such as cell proliferation and apoptosis,metabolism and signaling pathways.A lot of studies have indeed described the aberrant expression of miRNAs in human tumors and have investigated their potential role as oncogenes or tumor suppressor genes,depending on the targets they regulate.Furthermore,more and more studies have demonstrated that an important role of miRNAs in anticancer drug resistance and miRNA expression profiling can correlate with the development of anticancer drug resistance.A systematic and intensive study on the mechanisms of miRNA in anticancer drug resistance will provide us a strong rationale for the development of miRNA-based therapeutic strategies aiming to overcome cancer cell resistance.This paper has reviewed the recent development of miRNAs involved in anticancer drug resistance.

Clinical significance of cyclooxygenase-2 and BCRP expressions in non-Hodgkin lymphoma / 白血病·淋巴瘤

Objective To investigate the correlation and significance of cyclooxygenase-2 (COX-2)and the breast cancer resistance protein (BCRP) expressions in non-Hodgkin lymphoma(NHL). Methods Ten patients with reactive lymph nodes (RLN) were considered as a control group. Compared with β-actin as internal control, the BCRP mRNA expressions of 61 NHL samples and 10 lymph tissues in control group were detected by semi-quantitative revere transcription polymerase chain reaction (RT-PCR) assay, while the expressions of COX-2 protein of the above specimens were detected by SP immunohistochemistry. Results The positive rates of COX-2 and BCRP in NHL were 50.8 %(31/61) and 45.8 % (28/61), respectively , and were higher than those in the control group (P ＜0.05). The expression of COX-2 was statistically positive correlated to that of BCRP (X2 =8.795, r=0.355, P＜0.05). The expressions of COX-2 and BCRP were not correlated to clinical and pathological factors, such as age, sex, IPI, LDH, β2-microglobulin level and Ann Arbor stage, however, the expression of BCRP was statistically correlated to chemotherapy efficacy.Conclusion BCRP may be involved in multi-drug resistance (MDR) of NHL, so it may contribute to the assessment of chemotherapy and prediction of NHL. Since there is a strong correlation between COX-2 expression and MDR in NHL, the application of COX-2 inhibitors may enhance sensitivity of chemotherapy.

Correlation between the chemotherapy resistance of diffuse large B-cell lymphoma and cytokines IL-6 and IL-10 / 白血病·淋巴瘤

Objective To investigate the correlation between expression levels of serum cytokines IL-2,IL-6, IL-8, IL-10, TNF-α and IFN-γ in patients with diffuse large B-cell lymphoma(DLBCL) and chemotherapy resistance. Methods 30 cases of DLBCL patients with chemotherapy resistant, 30 cases of DLBCL patients with chemotherapy sensitive and 20 cases of healthy individuals as normal control group were enrolled. The levels of serum cytokines IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γbefore, during and after treatment in both DLBCL groups and normal control group were detected by ELISA assay. Results The expression level of serum IL-6 and IL-10 before treatment in DLBCL patients with chemotherapy resistance was significantly higher than that in DLBCL patients with chemotherapy sensitive and normal control group (P ＜ 0.05), however,that after treatment in DLBCL patients with chemotherapy resistance was significantly lower than that before treatment (P = 0.02, P = 0.015). The level of serum IL-6 and IL-10 in patients with DLBCL recurrence into drug resistance was higher than that during of remission (P = 0.004, P ＜0.001). Before treatment, the expression level of serum IL-6 in patients with Ⅲ-Ⅳ stage in chemotherapy resistant group was significantly higher than that in ones with Ⅰ - Ⅱ stage(P ＜0.05). Levels of IL-2, IL-8, TNF-α and IFN-γin chemotherapy resistant group, chemotherapy sensitive group and the normal control group were no differences (P ＞0.05).Conclusion The expression levels of the serum IL-6 and IL-10 were closely correlated with the chemotherapy efficacy of DLBCL, they may be involved in drug resistance of DLBCL.