Micro ribonucleic acid-448 regulates zinc finger e-box binding homeobox 1 to inhibit the growth of breast cancer cells and increase their sensitivity to chemotherapy

Abstract Objective: This study aimed to investigate the effect of Zinc Finger E-box Binding Homeobox 1 (ZEB1) regulation by Micro Ribonucleic acid (miR)-448 on Breast Cancer (BC) cells and their sensitivity to chemotherapy. Methods: miR-448 and ZEB1 mRNA levels in BC and normal tissues were detected by qPCR, and ZEB1 protein was detected by Western Blotting (WB). The correlation between miR-448 and tumor metastasis, clinical staging, and ZEB1 expression was analyzed. MCF-7 cells were transfected or co-transfected with the miR-448 mimic, oe-ZEB1, or their negative controls. Changes in miR-448 and ZEB1 expression were detected by qPCR and WB. Cell proliferation was determined by CCK-8 assays, invasion changes were analyzed by Transwell assays, and apoptosis was detected by flow cytometry. Results: miR-448 expression in BC tissues was lower than that in normal tissues, while ZEB1 expression was increased in the former. ZEB1 expression was lower in BC patients with lymph node metastasis than in those without. In patients with clinical stage I-III BC, miR-448 expression decreased with an increase in tumor stage, which was negatively correlated with ZEB1 expression. Upregulation of miR-448 expression can suppress MCF-7 cell proliferation and invasion and promote apoptosis. Upregulation of ZEB1 expression in cells overexpressing miR-448 can partially reverse the inhibition of BC cell growth induced by miR-448. miR-448 can enhance the sensitivity of cells toward paclitaxel and 5-fluorouracil. Conclusions: miR-448 suppresses cell proliferation and invasion and promotes apoptosis by targeting ZEB1. Moreover, it can increase the sensitivity of cells toward paclitaxel and 5-fluorouracil.

Analysis of Correlation between TTF-1 and Sensitivity to First-line Chemotherapy and Prognosis in Patients with Small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Thyroid transcription factor-1 (TTF-1) has been widely studied in non-small cell lung cancer, which is considered as an independent prognostic factor in patiens with non-small cell lung cancer. However, there are few studies on the prognostic value of TTF-1 in small cell lung cancer (SCLC). The purpose of this study was to explore the relationship between the expression state of TTF-1 and the sensitivity to first-line chemotherapy and prognosis in patients with SCLC.@*METHODS@#A retrospective analysis was made on 234 patients with SCLC who were diagnosed and treated in The Affiliated Hospital of Qingdao University and received platinum-based chemotherapy. The clinical characteristics, treatment and survival of the patients were followed up. Chi χ² test and Logistic regression model were used to analyze the relationship between TTF-1 expression and chemotherapy response rate. Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the effect of TTF-1 expression on survival time of patients.@*RESULTS@#Among the 234 patients, the positive expression of TTF-1 was 188 cases (80.3%), and the negative expression of TTF-1 was 46 cases (19.7%). The objective response rate (ORR) of first-line chemotherapy in patients with positive expression of TTF-1 was higher than that in patients with negative expression of TTF-1 (70.7% vs 47.8%) (χ²=8.681, P=0.003). Logistic regression multivariate analysis showed that the expression state of TTF-1 was an independent predictor of ORR in first-line chemotherapy (OR=0.216, 95%CI: 0.076-0.615, P=0.004), however this difference was only reflected in LS-SCLC. The median progression free survival (PFS) of patients with negative expression of TTF-1 was shorter than that of patients with positive expression (6.9 months vs 9.0 months) (χ²=9.357, P=0.002). The median OS in TTF-1 negative group was shorter than that in TTF-1 positive group (13.3 months vs 20.1 months)(χ²=12.082, P=0.001).@*CONCLUSIONS@#TTF-1 expression is an independent predictor of first-line chemotherapy response rate and survival in patients with SCLC, and may become a biomarker to predict the efficacy and prognosis of SCLC.

Astragalus polysaccharide may increase sensitivity of cervical cancer HeLa cells to cisplatin by regulating cell autophagy / 中国中药杂志

This study aimed to investigate the possible sensitivity of Astragalus polysaccharides, in order to improve the chemosensitivity of cervical cancer HeLa cells to cisplatin by regulating the cell autophagy, and explore its possible mechanism. In this study, HeLa cells were divided into control group, cisplatin group, Astragalus polysaccharide group, and Astragalus polysaccharide combined with cisplatin group. MTT assay was used to detect the proliferation of cervical cancer HeLa cells. Flow cytometry was used to detect the apoptosis and cycle of HeLa cells in each experimental group. RT-PCR was used to detect the mRNA expression of autophagy-related proteins beclin1, LC3Ⅱ and p62. The expression levels of autophagy-related proteins beclin1, LC3Ⅱ, LC3Ⅰ and p62 were detected by WB method. MTT results showed that compared with the control group, the proliferation of HeLa cells was significantly inhibited in each administration group(<0.05), and the inhibitory effect of the combination group was more significant(<0.01). The apoptotic rate of HeLa cells was significantly increased(<0.05), and the apoptotic rate of the combination group was significantly increased(<0.01) compared with the control group(<0.05).In conclusion, G₀/G₁ phase showed the most significant differences between the two groups. RT-PCR and WB results showed that the gene and protein expressions of beclin1 and LC3Ⅱ were up-regulated, while the gene and protein expressions of p62 were down-regulated compared with the control group. The above-mentioned changes in the combination group were more significant. Through the analysis of the above experimental results, it is speculated that Astragalus polysaccharides may increase the sensitivity of cervical cancer HeLa cells to cisplatin by regulating the cell autophagy. Its possible mechanism of action is correlated with the up-regulation of autophagy-related proteins beclin1, the promote the conversion from LC3Ⅰ to LC3Ⅱ, the down-regulation of labeled protein p62, and the enhancement of HeLa cell autophagic activity, thereby increasing the sensitivity of HeLa cells to cisplatin chemotherapy.

A preliminary study of amino acid metabolomics using LC-MS/MS to predict the che-motherapeutic response of patients with advanced breast cancer / 中国肿瘤临床

Objective:To investigate the value of amino acid metabolomics in evaluating chemotherapeutic response of patients with ad-vanced breast cancer, the changes in the levels of 32 amino acids in the circulating serum of patients before (baseline) and after the first cycle (prognosis) of chemotherapy were tested. Methods:Seventy-three advanced breast cancer patients with local recurrence and distant metastasis admitted at the Liaoning Cancer Hospital from March 2015 to October 2016 were enrolled. Peripheral blood samples (2 mL) were collected before and after the first cycles of chemotherapy from each patient. Thirty-two amino acids in the se-rum were tested using the ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients were catego-rized into the improvement or deterioration groups, based on the first imaging test after 2-4 cycles of chemotherapy. The changes in amino acids levels were analyzed in different prognosis groups. Results:The levels of the 32 amino acids ranged 3-180000 pmol/L. Compared to their baseline levels, both glycine and L-glutamine increased in the improvement group, but decreased in the deteriora-tion group. Sarcosine was significantly reduced in the improvement group, while differences in its levels were not obvious in the deteri-oration group. L-threonine, taurine, iminodiacetic acid, and L-glutamic acid were increased in both groups. Conclusion:Changes in the serum levels of glycine, sarcosine, and the other amino acids before and after the first cycles of chemotherapy can predict chemothera-peutic response in patients with advanced breast cancer. Amino acid metabolomics may become a potential biomarker for predicting the efficacy of chemotherapy earlier than that of imaging tests, and thereby help improve therapeutic strategies for advanced breast cancer.

Study on the Relationship between Cisplatin-resistance of Human Ovarian Cancer Cell and TLR9 under Hypoxia / 中国药房

OBJECTIVE:To study the relationship between cisplatin-resistant of human ovarian cancer cells (SKOV3) and Toll-like receptor 9 (TLR9) under hypoxia. METHODS:Immunofluorescence method was used to detect the TLR9 expression in rupture and intact membranes SKOV3. SKOV3 was taken,adding cisplatin,then CCK-8 was used to detect cell inhibition rate af-ter 6,12,24 h of added into TLR9 specific agonists CpG-ODN 2006 (group A) and its isotype control CpG-ODN 2006 control (group B). SKOV3 or SKOV3 pretreated by 0(not added),1,10,102,103 μmol/L TLR9 specific antagonist chloroquine for 3 h were taken,adding cisplatin,cell inhibition rate was detected after 24 h of added into SKOV3 normoxia(21% O2),hypoxia(1%O2)incubating 6,12,24 h,HICR under hypoxia in pretreatment was calculated. Western blot method was used to detect the multi-drug resistance associated protein(MRP)expression in SKOV3 under the conditions of normoxia 24 h cell supernatant(group C), hypoxia 24 h cell supernatant(group D),hypoxia 24 h cell supernatant+10 μmol/L chloroquine(group E). RESULTS:TLR9 was expressed in both cell membrane and cytoplasm of SKOV3. Compared with group A,cell inhibition rate in group B was decreased (P<0.01). Compared with normoxia cell supernatant,cell inhibition rate was decreased after hypoxia cell supernatant (P<0.05). Compared with not added chloroquine,adding 10,102 μmol/L chloroquine can obviously decrease HICR(P<0.01),and the most significant decrease was showed when using hypoxia 24 h cell supernatant+10 μmol/L chloroquine. Compared with group C,MRP expression in group D was strengthened (P<0.01);compared with group D,MRP expression in group E was weakened (P<0.01). CONCLUSIONS:TLR9 receptors can be activated under hypoxia,and cause SKOV3 to cisplatin-resistance,the effect may be related with up-regulating MRP expression.

Effect of intratumor heterogeneity of esophageal squamous cell carcinoma on chemotherapy sensitivity / 中华肿瘤杂志

Objective@#To investigate the relationship of heterogeneity of esophageal squamous cell carcinoma (ESCC) and chemotherapy sensitivity.@*Methods@#Five different region specimens isolated from primary tumor(R1~R5)and 1 specimen(R6)isolated from adjacent non-neoplastic tissue from 10 ESCC patients who underwent surgical treatment were cultured in vitro. The inhibitory effect of cisplatin on proliferation of ESCC cells from different regions was determined by methyl thiazolyl tetrazolium (MTT). The cell cycle and apoptosis induced by cisplatin was determined by flow cytometry (FCM) analysis. The mRNA levels of ATP7A and ATP7B were determined by quantitive RT-PCR (qRT-PCR).@*Results@#The result showed that different regions of each specimen exhibited different chemotherapy sensitivity to cisplatin, and the cell survival rates of region R6 of each specimen were higher than other regions from the same specimen. The cell survival rate of region R3 from the tenth specimen was (81.42±8.84)%, which is significantly higher than (11.90±2.75)% of region R5 (P<0.01). FCM analysis showed that significant differences of early apoptosis and later apoptosis were observed in six specimens induced by cisplatin (P<0.05), and significant differences of cell cycle and G1 period were observed in seven specimens (P<0.05). The qRT-PCR results showed that the mRNA level of ATP7A in region R1, R2, R3, R4 and R5 was (100.00±3.42)%, (118.10±2.21)%, (75.40±4.15)%, (95.40±3.32)% and (41.70±2.57)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7A in region R6 was (175.20±5.32)%, significantly higher than those of regions from R1 to R5 (P<0.05). The mRNA level of ATP7B in region R1, R2, R3, R4 and R5 was (100.00±4.89)%, (73.60±2.65)%, (175.60±6.12)%, (46.10±4.62)% and (363.70±8.67)%, respectively, with significant differences (P<0.05). The mRNA level of ATP7B in region R6 was (1 165.40±7.25)%, significantly higher than those of regions from R1 to R5 (P<0.05).@*Conclusion@#The intratumor heterogeneity of ESCC results in the heterogeneity of resistance to cisplatin, which affects the chemotherapeutic effect.

Association between MTHFR C677T polymorphism and susceptibility of 5-FU chemotherapy regimens in the treatment of gastrointestinal cancer: A Meta-analysis / 肿瘤

Objective: To systematically evaluate the association between methylenetetrahydrofolatereductase (MTHFR ) C677T gene polymorphism andthe sensitivity of 5-fluorouracil (5-FU) chemotherapy regimens in thetreatment of gastrointestinal cancer.Methods: Such databases as PubMed, EBSCO, Web of Science,Cochrane Library, Chinese BioMedical Literature Database (CBM),China National Knowledge Infrastructure (CNKI), VIP and WanFangData were systematically searched to collect studies on theassociation between MTHFR C677T gene polymorphism and thesensitivity of 5-FU chemotherapy regimens in the treatment ofgastrointestinal cancer published from each database establishingtime to December 2016. All of subjects were selected by tworeviewers, and the data were extracted according to the inclusionand exclusion criteria. Meta- analysis was performed using RevMan5.3 statistical software, the sensitivity analysis and publication biasassessment were performed using STATA 12.0 statistical software.Resul t s : A total of 11 studies involving 1 267 patients withgastrointestinal cancer were included. The sensitivity of patients withMTHFR 677T allele to 5-FU chemotherapy regimens was significantlyhigher than that of patients with C allele [odds ratio (OR ) = 5.31,95% confidence interval (CI ): 3.23-8.73, P < 0.001]. The sensitivity ofpatients carried TT allele to chemotherapy regimens was significantlyhigher than that of patients carried CC allele (OR = 4.87, 95% CI :2.18-10.86, P < 0.001). The sensitivity of patients with TT + TCgenotype to chemotherapy regimens was significantly higher thanthat of patients with CC genotype (OR = 0.52, 95% CI : 0.33-0.84, P =0.007). TT genotype patients were significantly more sensitive tochemotherapy as compared with CC + TC genotype patients (OR =4.39, 95% CI : 2.07-9.32, P < 0.001).Co n c l u s i o n : The pol ymorphi sm of MTHFR C677T gene ingastrointestinal cancer patients is significantly correlated with thesensitivity of 5-FU chemotherapy regimen.

Predictive value of Annexin A3 protein expression in peripheral blood and tumor tissue for platinum resistance in ovarian epithelial cancer / 重庆医学

Objective To compare the values of peripheral blood and tumor tissue Annexin A3 protein expressions for predictinge platinum resistance in ovarian epithelial cancer. Methods A total of 72 cases of newly treated ovarian epithelial cancer and undergoing platinum based chemotherapy after surgery,and completely followed up in this hospital from February 2010 to February 2012 were selected and divided into the platinum-sensitive group(54 cases) and platinum-resistant group(18 cases) according to the platinum resistance evaluation criteria. Peripheral blood Annexin A3 level was detected by chemiluminescence immunoassay. Tumor tissue Annexin A3 level was detected by adopting the immunohistochemical staining. The predictive value of peripheral blood and tumor tissue Annexin A3 for predicting platinum resistance was analyzed by drawing the ROC curve. Results The peripheral blood Annexin A3 level in the platinum-sensitive group was significantly lower than that in the platinum-resistant group,the difference was statistically significant(P<0.05), the positive rate of tumor tissue Annexin A3 expression in the platinum sensitivity group was significantly lower than that of platinum-resistant group(P<0.05). The median survival time in peripheral blood Annexin A3 low concentration group was significantly higher than that of high concentration group(31.2 months vs. 20.4 months, P<0.05). The median survival time in tissue Annexin A3 low expression group was significantly higher than that in the high expression group (35.2 months vs. 23.1 months P<0.05). The multivariate analysis showed that the level of Annexin A3 expression in serum and tumor tissue were the independent risk factor for affecting platinum resistance (all P<0.05). The area of curve (AUC) of peripheral blood Annexin A3 in predicting platinum resistance was 0. 821, which of tissue Annexin A3 in predicting platinum was 0. 763, peripheral blood Annexin A3 for predicting platinum resistance was significantly higher than tissue Annexin A3 (P< 0.05). Conclusion The expression levels of Annexin A3 protein in peripheral blood and tumor tissue are significantly increased in the patients with platinum resistant ovarian cancer,the predictive value of Annexin A3 protein in peripheral blood for platinum resistance is better than that of tissue Annexin A3 protein.

Study on the Correlation between RRM1 Single Nucleotide Polymorphisms and Chemotherapy Sensitivity of NSCLC Patients for Gemcitabine / 中国药房

OBJECTIVE:To investigate the correlation between ribonucleotide reductase M1 subunit (RRM1) single nucleo-tide polymorphisms (SNPs) and chemotherapy sensitivity of patients with non-small cell lung cancer (NSCLC) for gemcitabine. METHODS:A total of 96 NSCLC patients receiving primary treatment selected from our hospital during Aug. 2014-Jul. 2016 were all accepted gemcitabine-based two-drug chemotherapy plan,with continuous treatment for at least 2 cycles(28 d as a cycle). Che-motherapy sensitivity rate was calculated by using the ratio of the sum of patients with complete response and partial response to the sum of test patients. RRM1 genotype was tested by PCR and direct sequencing. The correlation between different genotypes and chemotherapy sensitivity was analyzed. RESULTS:Distribution frequency of RRM1-37C>A CC, CA, AA genotype were 35.42％,52.08％,12.50％,respectively;distribution frequency of-524C>T CC,CT,TT genotype were 18.75％,37.50％, 43.75％,respectively. The frequency of each genotype was in the line with Hardy-Weinberg equilibrium(P>0.05). Chemotherapy sensitivity rate of 96 NSCLC patients was 37.50％. The patient's age,sex,ethnicity,smoking or not,TNM stage,pathological type,chemotherapy plan,and the Eastern American Oncology Collaboration score were not associated with chemotherapy sensitivi-ty (P>0.05). Chemotherapy sensitivity rates of RRM1(-37CA)+(-524CT)genotype and (-37CC)+(-524TT) genotype patients (57.14％,39.39％) were significantly higher than those of other genotype patients (10.71％),with statistical significance (P<0.05). There was no statistical significance in chemotherapy sensitivity rate between RRM1(-37CA)+(-524CT) and (-37CC)+(-524TT)genotype patients. CONCLUSIONS:In NSCLC patients,the SNPs of RRM1 can be used as predictive factor for the sen-sitivity of gemcitabine chemotherapy,and RRM1(-37CA)+(-524CT)and(-37CC)+(-524TT)genotype patients have higher sensi-tivity to this type of chemotherapy.

Enhancement of IL-37 in chemosensitivity of cervical cancer HeLa cells to cisplatin / 吉林大学学报(医学版)

Objective:To transfer the interleukin 37 (IL-37) gene to cervical cancer Hela cells,and to explore the killing effect of IL-37 on the HeLa cells and its enhancement in the chemotherapy sensitivity of HeLa cells.Methods:The pIRES2-EGFP (NC group) and pIRES2-EGFP/IL-37 (IL-37 group) plasmids were transfected into the HeLa cells.Q-PCR and Western blotting methods were used to detect the expression levels of IL-37 mRNA and protein.The activities of HeLa cells in NC group,IL-37 group,DDP group and IL-37+DDP group were detected by CCK8 method,and the inhibitory rates of cells were calculated.The gene expressions of signal transducer and activator of transcription 3 (STAT3) and Cyclin D1 were detected by RT-PCR method.Results:Compared with NC group,the expression levels of IL-37 mRNA and protein in IL-37 group were significantly increased (P＜0.01).The activities of HeLa cells in DDP (5-15 mg · L-1) groups were inhibited after administration for 24-72 h (P＜ 0.01);the inhibitory rates in IL-37 + DDP group were higher than those in DDP group within 48 h after administration (P＜0.05).Compared with IL-37 group,the inhibitory rates in IL-37+DDP group was increased with 96 h after administration (P＜0.05).Compared with NC group,the expression levels of STAT3 and Cyclin D1 mRNA in IL-37 group were significantly decreased (P＜0.01).Conclusion:The over-expression of IL-37 can inhibit the proliferation of cervical cancer cells and enhance the effect of DDP on the chemotherapy of cervical cancer cells which may be related to the down-regulation of the expressions of STAT3 and Cyclin D1 by IL-37.

The evaluation value analysis of serum CEA and CA15-3 levels in breast cancer on chemotherapy curative prognosis evaluation / 国际检验医学杂志

Objective To investigate the value of serum CEA and CA15-3 in the evaluation of breast cancer chemotherapy and prognosis.Methods 63 breast cancer patients were retrospectively analyzed from May 2011 to June 2012 in our Hospitals as breast cancer group,according to the situation of survival would be divided into survival group(n=42) and death group(n=21) and select indicators for outpatient medical normal crowd 63 cases as normal group.Serum levels of CEA and CA15-3 were measured by fluorescence immunoassay for 4 years.The prognosis of all patients was analyzed statistically.Results Serum level of CEA and CA15-3 in Ⅳ period breast cancer patients was obviously higher than Ⅲ period,the difference was statistically significant(P＜ 0.05).Chemotherapy efficient of CEA,CA15-3,CEA and CA15-3 express in negative group were obviously higher than positive group,the difference was statistically significant(P＜0.05).All patients were followed up for 1 to 4 years with an average follow-up time of 3.63 years and 42 patients survived for more than 4 years.CEA positive group patients of 4 years survival rate(55.26％) was obviously lower than negative group(84.00 ％),the difference was statistically significant(P＜0.05).CA15-3positive group patients of 5 years survival rate(52.78％) was obviously lower than negative group(85.19 ％),the difference was statistically significant(P＜ 0.05).CEA and CA15-3 positive group patients of 5 years survival rate (52.38％) was obviously lower than negative group (95.24％),the difference was statistically significant (P ＜ 0.05).Before treatment the serum CEA and CA15-3 level Survival groups was lower than death group,the difference was statistically significant(P＜0.05).Conclusion Detection of serum CEA and CA15-3 levels in patients with breast cancer before chemotherapy can provide reference data for chemotherapy efficacy and prognosis evaluation.Detection of breast cancer patients with chemotherapy before serum CEA and CA15-3 levels can provide reference for chemotherapy curative effect and prognosis assessment data.

Enhancement of IL-37 in chemosensitivity of cervical cancer HeLa cells to cisplatin / 吉林大学学报(医学版)

Objective:To transfer the interleukin 37 (IL-37) gene to cervical cancer Hela cells,and to explore the killing effect of IL-37 on the HeLa cells and its enhancement in the chemotherapy sensitivity of HeLa cells.Methods:The pIRES2-EGFP (NC group) and pIRES2-EGFP/IL-37 (IL-37 group) plasmids were transfected into the HeLa cells.Q-PCR and Western blotting methods were used to detect the expression levels of IL-37 mRNA and protein.The activities of HeLa cells in NC group,IL-37 group,DDP group and IL-37+DDP group were detected by CCK8 method,and the inhibitory rates of cells were calculated.The gene expressions of signal transducer and activator of transcription 3 (STAT3) and Cyclin D1 were detected by RT-PCR method.Results:Compared with NC group,the expression levels of IL-37 mRNA and protein in IL-37 group were significantly increased (P＜0.01).The activities of HeLa cells in DDP (5-15 mg · L-1) groups were inhibited after administration for 24-72 h (P＜ 0.01);the inhibitory rates in IL-37 + DDP group were higher than those in DDP group within 48 h after administration (P＜0.05).Compared with IL-37 group,the inhibitory rates in IL-37+DDP group was increased with 96 h after administration (P＜0.05).Compared with NC group,the expression levels of STAT3 and Cyclin D1 mRNA in IL-37 group were significantly decreased (P＜0.01).Conclusion:The over-expression of IL-37 can inhibit the proliferation of cervical cancer cells and enhance the effect of DDP on the chemotherapy of cervical cancer cells which may be related to the down-regulation of the expressions of STAT3 and Cyclin D1 by IL-37.

The evaluation value analysis of serum CEA and CA15-3 levels in breast cancer on chemotherapy curative prognosis evaluation / 国际检验医学杂志

Objective To investigate the value of serum CEA and CA15-3 in the evaluation of breast cancer chemotherapy and prognosis.Methods 63 breast cancer patients were retrospectively analyzed from May 2011 to June 2012 in our Hospitals as breast cancer group,according to the situation of survival would be divided into survival group(n=42) and death group(n=21) and select indicators for outpatient medical normal crowd 63 cases as normal group.Serum levels of CEA and CA15-3 were measured by fluorescence immunoassay for 4 years.The prognosis of all patients was analyzed statistically.Results Serum level of CEA and CA15-3 in Ⅳ period breast cancer patients was obviously higher than Ⅲ period,the difference was statistically significant(P＜ 0.05).Chemotherapy efficient of CEA,CA15-3,CEA and CA15-3 express in negative group were obviously higher than positive group,the difference was statistically significant(P＜0.05).All patients were followed up for 1 to 4 years with an average follow-up time of 3.63 years and 42 patients survived for more than 4 years.CEA positive group patients of 4 years survival rate(55.26％) was obviously lower than negative group(84.00 ％),the difference was statistically significant(P＜0.05).CA15-3positive group patients of 5 years survival rate(52.78％) was obviously lower than negative group(85.19 ％),the difference was statistically significant(P＜ 0.05).CEA and CA15-3 positive group patients of 5 years survival rate (52.38％) was obviously lower than negative group (95.24％),the difference was statistically significant (P ＜ 0.05).Before treatment the serum CEA and CA15-3 level Survival groups was lower than death group,the difference was statistically significant(P＜0.05).Conclusion Detection of serum CEA and CA15-3 levels in patients with breast cancer before chemotherapy can provide reference data for chemotherapy efficacy and prognosis evaluation.Detection of breast cancer patients with chemotherapy before serum CEA and CA15-3 levels can provide reference for chemotherapy curative effect and prognosis assessment data.

Targeting BCRP/ABCG2 by RNA Interference Enhances the Chemotherapy Sensitivity of Human Colon Cancer Side Population Cells / 华中科技大学学报（医学）（英德文版）

Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population (SP) cells from a colon cancer cell line (Colo-320) and examined their self-renewal and differentiation abilities.Compared to non-SP (NSP) cells,SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies.Additionally,more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2.We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like,small interfering RNA (siRNA) eukaryotic expression plasmid targeting BCRP/ABCG2.

Effect of small interference RNA silenced S100A4 protein in human gastric carcinoma cells on proliferation, apoptosis and chemotherapy sensitivity in vitro / 国际外科学杂志

Objective To study the application of small interfering RNA silencing S100A4 protein in human gastric cancer cell BGC-823 proliferation,apoptosis and the effect of chemotherapy sensitivity.Methods Human gastric carcinoma cell line BGC-823 transfection siRNA,RT-PCR detected the changes of mRNA after transfection.Groups divided into interference group,negative control group and normal control group.MTT test determined different concentrations of oxaliplatin in gastric cancer cells and calculated IC50,then draw cell growth curve,TUNEL method to detect apoptosis,RT-PCR tested each cell mRNA changed,Western blot detected the change of the S100A4 protein.All data analysis by SPSS17.0,t test applied,RT-PCR and Western blot results analysis by SPSS17.0,comparing multiple samples by using single factor analysis of variance and LSD test.P ＜ 0.05 was statistically significant.Results RT-PCR results showed that BGC-823 cell transfection,S100A4mRNA expression quantity respectively after 48 hours:(0.674+0.011),(0.652+0.021),(0.345 + 0.040),the interference group and normal control group were statistically significant (P =0.012,P ＜ 0.05) and the negative control group with interference group differences were statistically significant (P =0.000,P ＜ 0.05),and normal control group was no statistically significant difference with the negative control group (P =0.380,P ＞ 0.380);Western blot results showed BGC-823 cell transfection S100A4 expression significantly lowered respectively after 48 hours,there were (0.654 + 0.025),(0.642 + 0.014),(0.317 ± 0.061),the interference group and normal control group was statistically significant (P =0.01,P ＜ 0.05),between negative control group and interference group were statistically significant (P =0.000,P ＜ 0.05),normal control group and the negative control group had no significant difference (P =0.341,P ＞ 0.341).After S100A4-siRNA transfection,gastric carcinoma BGC-823 cell proliferation decreased,TUNEL method showed obviously increase apoptosis,MTY showed that IC5o of oxaliplatin was 56.31 μmol/L,after transfection,IC50 was 0.654 μmol/L.Conclusions This study showed that the siRNA silence S100A4 protein inhibit gastric cancer cell proliferation,induced apoptosis and improved chemotherapy sensitivity of oxaliplatin.S100A4 might be prompt targets for the treatment of gastric carcinoma.

Effect of Wip1 gene silencing on chemotherapy sensitivity of human colon cancer cells / 中国病理生理杂志

AIM:To observe the inhibitory effect of siRNA targeting to Wip1 gene on the Wip1 gene expression in the colon cancer cells and to investigate the influence of Wip1 gene silencing on the chemotherapy sensitivity of colon cancer cells.METHODS:Wip1-811 siRNA targeting to Wip1 gene was transfected into RKO colon cancer cells with high expression of Wip1 gene.The mRNA expression of Wip1 was measured by real-time PCR.The protein level of Wip1 was detected by Western blotting.The viability of RKO colon cancer cells was measured by MTS assay.The cell apoptosis and cell cycle were analyzed by flow cytometry.RESULTS: Wip1-811 siRNA efficiently inhibited the expression of Wip1 at mRNA and protein levels.The enhanced chemotherapy sensitivity of RKO colon cancer cells was observed after inhibition of Wip1 gene expression.The viability of RKO colon cancer cells was decreased from (89.4 ±6.6)%to (74.7 ±3.9)%af-ter treated with 5-fluorouracil (P<0.05) and decreased from (77.9 ±2.4)%to (66.7 ±2.9)%after treated with oxali-platin ( P<0.05 ) .The cell apoptotic rate was increased from ( 7.7 ±0.5 )% to ( 12.3 ±3.2 )% and from ( 14.7 ± 2.1)% to (34.0 ±2.1)% when RKO colon cancer cells were treated with 5-fluorouracil and oxaliplatin, respectively (P<0.05).CONCLUSION:Wip1 gene silencing enhances chemotherapy sensitivity of colon cancer cells.

Effect of chemotherapy sensitivity enhancement by RNA interference targeting p21-activated kinase 1 with 5-fluorouracil on human colon cancer cells / 实用医学杂志

Objective To investigate the effect of p21-activated kinase 1 on chemotherapy sensitivity of 5-fluorouracil. Methods Cell proliferation was measured by CCK8 and apoptosis rate by flow cytometry or Hoechst staining; the expression of Bcl-xl, Bcl-2, XIAP were determined by Western Blot. Results 5-FU combined shRNA-Pak1 group (combination group) could be significantly inhibited in terms of proliferation (P <0.05). The percentage of apoptosis rate in combined group was the highest and the difference among groups indicated statistical significance (P < 0.05). The expression of Bcl-xl, Bcl-2, XIAP in combination group was significantly inhibited compared with 5-FU group or shRNA-Pak1 group. Conclusion PAK1 inhibited by RNA interference can enhance chemotherapy sensitivity of 5-Fu on growth inhibition and apoptosis induction in colon cancer significantly.

Relation between breast cancer related gene BRCA1 and the sensitivity to docetaxel chemotherapy / 中华内分泌外科杂志

Objective To investigate the relationship between the expression of BRCA1 in breast cancer tissues and the sensitivity to docetaxel chemotherapy.Methods The expression of BRCA1 was detected by immunohistochemical method and the new adjuvant chemotherapy containing docetaxel chemotherapy regimen (TEC)was given.The relationship between BRCA1 expression and efficacy of neoadjuvant chemotherapy with docetaxel was studied.Results The rate of complete response,partial response,stable disease and progress disease was 22.6％,71.7％,5.7％,and 0％ respectively in breast cancer patients with positive BRCA1 expression and 11.8％,58.9％,27.4％,and 2.0％ in breast cancer patients with negative BRCA1 expression.The difference between the 2 groups had statistical significance.Conclusion BRCA1 expression has a positive relationship with sensitivity to chemotherapy regimen containing docetaxel chemotherapy regimens (TEC),and can be used as a good marker for predicting efficacy of chemotherapy and screening agents.

The current status of prediction of neoadjuvant chemotherapy sensitivity via biological characteristics in breast cancer / 肿瘤

Chemotherapy, which includes preoperative chemotherapy (neoadjuvant chemotherapy) and postoperative chemotherapy, is one of the most important parts of systemic therapy in breast cancer. However, not every patient is sensitive to the chemotherapy. In recent years, it is reported that, apart from those of the tumor cells, the characteristics of stromal components could also affect the effectiveness of neoadjuvant chemotherapy, which include markers of immune cells, stromal fibroblasts, proteomic and genomic markers, etc. These researches bring new approaches to adjust the regimen and improve the effectiveness of neoadjuvant chemotherapy. This article aims at reviewing and summarizing the literature at these points. Copyright © 2012 by TUMOR.

Insulin in Endometrial Carcinoma Chemotherapy: A Beneficial Addition and not a Problem / 华中科技大学学报（医学）（英德文版）

The effects of insulin or insulin in combination with chemotherapeutic drugs on the proliferation and apoptosis of endometrial carcinoma cells were examined with an aim to determine the efficacy and safety of insulin in endometrial cancer therapy. Ishikawa and Hec-lA cells were treated with insulin and/or paclitaxel. Cell proliferation was assessed by MTT assay. Cell cycle and cell apoptosis were determined by flow cytometry (FCM). Survivin gene expression was detected by RT-PCR. Our results showed that in a certain range of working concentrations and action time, insulin could mildly augment cell proliferation and the percentage of S phase cells in endometrial cancer (Ishikawa/Hec-lA) cells. Insulin plus paclitaxel (combination group) could significantly inhibit cell proliferation (69.38%±2.32% vs 40.31%±4.52% with Ishikawa; 64.11%±6.33% vs 45.89%±3.27% with Hec-lA) and increase cell apoptosis compared with treatment with paclitaxel alone (paclitaxel group). Survivin gene expression was also significantly decreased in combination group as compared with paclitaxel group. We are led to conclude that insulin can mildly augment cell proliferation and present chemotherapy sensitivity in endometfial cancer cells. Insulin can be to used safely and efficiently in endometrial cancer therapy.