The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class Ⅲ β-tubulin protein expression in non-small cell lung cancer patients

Objective To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class Ⅲβ-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage Ⅲβ/Ⅳ non-small cell lung cancer(NSCLC) patients. Methods A total of 92 stage Ⅲβ/Ⅳ NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class Ⅲβ-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR) , overall survival (OS) and time to tumor progression (TTP) were assessed. Results Among the 87 evaluated patients, the positive expression rates of BRCA1 and class Ⅲβ-tubulin were 57. 5% (50/87) and 48. 3%(42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class Ⅲβ-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class 1 p-tubulin) ,group B (high expression of both BRCA1 and class Ⅲβ-tubulin) , group C (high expression of only BRCA1) and group D (high expression of only class Ⅲβ-tubulin). The RR was higher in group A than other three groups (60. 7% , 34. 8% , 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539. 4 ± 17. 6) days, (267. 2 ± 20. 5) days, (325. 6 ± 24. 1) days and (283.7±26.2) days respectively ; TTP: (256. 9 ± 28. 4) days, (143.8±17.6) days, (179. 3 ± 19. 8)days and (152. 6 ±23. 5) days respectively]. There were no significant differences among the other three groups. Conclusions The expression level of BRCA1 and class Ⅲβ-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class Ⅲβ-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.     

The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class Ⅲ β-tubulin protein expression in non-small cell lung cancer patients

Objective To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class Ⅲβ-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage Ⅲβ/Ⅳ non-small cell lung cancer(NSCLC) patients. Methods A total of 92 stage Ⅲβ/Ⅳ NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class Ⅲβ-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR) , overall survival (OS) and time to tumor progression (TTP) were assessed. Results Among the 87 evaluated patients, the positive expression rates of BRCA1 and class Ⅲβ-tubulin were 57. 5% (50/87) and 48. 3%(42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class Ⅲβ-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class 1 p-tubulin) ,group B (high expression of both BRCA1 and class Ⅲβ-tubulin) , group C (high expression of only BRCA1) and group D (high expression of only class Ⅲβ-tubulin). The RR was higher in group A than other three groups (60. 7% , 34. 8% , 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539. 4 ± 17. 6) days, (267. 2 ± 20. 5) days, (325. 6 ± 24. 1) days and (283.7±26.2) days respectively ; TTP: (256. 9 ± 28. 4) days, (143.8±17.6) days, (179. 3 ± 19. 8)days and (152. 6 ±23. 5) days respectively]. There were no significant differences among the other three groups. Conclusions The expression level of BRCA1 and class Ⅲβ-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class Ⅲβ-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.     

非小细胞肺癌患者肿瘤组织乳腺癌易感基因1和β微管蛋白Ⅲ表达及其与化疗疗效的关系

目的 观察肿瘤组织乳腺癌易感基因1(BRCA1)、β微管蛋白Ⅲ表达与ⅢB和(或)Ⅳ期非小细胞肺癌(NSCLC)采用紫杉醇联合顺铂(TP)方案化疗疗效的相关性.方法 入选初治、NSCLC临床TNM分期为ⅢB和(或)Ⅳ期、体能状态(PS)评分0～2分、预计生存期≥3个月的患者入选本研究.入选者均进行TP方案化疗,每3周重复,每2个周期评价1次疗效,共4～6个周期,无效者更换二线化疗方案.免疫组化检测肿瘤组织中BRCA1、β微管蛋白Ⅲ表达.根据BRCA1、β微管蛋白Ⅲ表达高低分为A组(BRCA1、β微管蛋白Ⅲ低表达)、B组(BRCA1、β微管蛋白Ⅲ高表达)、C组(BRCA1高表达,β微管蛋白Ⅲ低表达),D组(BRCA1低表达,B微管蛋白Ⅲ高表达).评价疗效指标:客观反应率(RR)、总生存时间(OS)、至肿瘤进展时间(TTP).结果 (1)人组87例ⅢB/Ⅳ期NSCLC患者,BRCA1、β微管蛋白Ⅲ表达阳性率分别为57.5%(50/87)、48.3%(42/87),BRCA1、β微管蛋白Ⅲ不同表达的NSCLC患者间临床特征比较差异无统计学意义.(2)87例患者中A组28例,B组23例,C组19例,D组17例.化疗前4组患者间的临床特征比较差异无统计学意义.4组患者RR分别为60.7%、34.8%、9/19、6/17;OS分别为(539.4±17.6)d、(267.2±20.5)d、(325.6±24.1)d、(283.7±26.2)d;TTP分别为(256.9±28.4)d、(143.8±17.6)d、(179.3±19.8)d、(152.6±23.5)d.方差分析显示,A组的RR、OS、TTP均优于其他3组,差异有统计学意义(P值分别为0.039、0.000和0.000).结论 BRCA1、β微管蛋白Ⅲ可作为TP方案疗效的预测分子;仅BRCA1、β微管蛋白Ⅲ低表达的NSCLC患者,可能是TP化疗方案的优势人群.

Abstract：

Objective To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class Ⅲβ-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage Ⅲβ/Ⅳ non-small cell lung cancer(NSCLC) patients. Methods A total of 92 stage Ⅲβ/Ⅳ NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class Ⅲβ-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR) , overall survival (OS) and time to tumor progression (TTP) were assessed. Results Among the 87 evaluated patients, the positive expression rates of BRCA1 and class Ⅲβ-tubulin were 57. 5% (50/87) and 48. 3%(42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class Ⅲβ-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class 1 p-tubulin) ,group B (high expression of both BRCA1 and class Ⅲβ-tubulin) , group C (high expression of only BRCA1) and group D (high expression of only class Ⅲβ-tubulin). The RR was higher in group A than other three groups (60. 7% , 34. 8% , 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539. 4 ± 17. 6) days, (267. 2 ± 20. 5) days, (325. 6 ± 24. 1) days and (283.7±26.2) days respectively ; TTP: (256. 9 ± 28. 4) days, (143.8±17.6) days, (179. 3 ± 19. 8)days and (152. 6 ±23. 5) days respectively]. There were no significant differences among the other three groups. Conclusions The expression level of BRCA1 and class Ⅲβ-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class Ⅲβ-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.     

Expression of E-selectin, integrinβ_1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance

AIM: To study the expression levels of E- selectin, integrinβ1 and immunoglobulin supperfamily member-intercellular adhesion molecule-1 (ICAM-1) in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma. METHODS: The serum contents of E-selectin, integrinβ1 and ICAM-1 were detected by enzyme-linked immuno-sorbent assay (ELISA), in 47 healthy individuals (control group) and in 57 patients with gastric carcinoma (gastric carcinoma group) respectively prior to operation and 7 d after operation. RESULTS: The serum E-selectin, ECAM-1 and integrinβ1 were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrinβ1 were significantly higher in gastric carcinoma patients than in controls (P < 0.01). A comparison of the E-selectin levels between the two groups showed statistically insignificant differnce (P = 0.64). In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients. CONCLUSION: Serum E-selectin, ICAM-1 and integrin pi expression levels are probably related to the metastasis and relapse of gastric cancer.     

Transforming growth factor—β1in invasion and metastasis in colorectal cancer

AIM：To investigate the role of TGFβ1 in invasion and metastasis in colorectal cancer by analysing TGFβ1 correlated wity depth of tumor invasion,stage and metastasis.METHODS:Serum TGFβ1levels were determined in50patients with colorectal cancer and 30healthy volunteers using a TGFβ1 enzyme-linked immunosorbent assay.TGFβ1 expression in primary and lymph node metastatic lesions were detected in 98cases of colorectal cancer by immunohistochemical staining and in situ hybridization.RESULTS:Serum levels of TGFβ1 in patients with colorectal cancer(40&#177;18μg&#183;L^-1)were significantly higher than those in the healthy control group(19&#177;8μg&#183;L^-1),P&lt;0.05.Elevated levels of serum TGFβ1were found in 60%of patients with colorectal cancer when the mean+2s was used as the upper limit of the normal range(35.1μg&#183;L^-1).Increases in serum TGFβ1 levels were significantly asociated with Dukei‘s stage(P&lt;0.05),but there was no significant difference between,Duki‘s stage Bpatients and Dukei‘s stage Cpatients.In the cytoplasm of cancer cells,TGFβ1 was immunostained in37.8%(37/98)of colorectal cancer,and this expression was confirmed by in situ hybridization,Among35cases of colorectal cancer with lymph node metastatic lesions,TGFβ1 positive staining was found in18(51.4%)cases of primary tumor,and 25(71.4%)cases with lymph node metastatic lesions,respectively,Of17cases with no staining in the primary lesion.7(41.2%)casesshowed TGFβ1 staining in the metastatic lesion.Serum TGFβ1 levels and TGFβ1 expression in colorectal cancer tissues were correlated significantly with depth of tumor invasion,stage and metastasis,Patients in stage C-D,T3-T4and with metastasis had significantly higher TGFβ1 levels than patients in stage A-B,T1-T2and without metastasis(P&lt;0.05).CONCLUSION:These results suggest that transforming growth factor-β1 is closely related to the invasion and metastasis of colorectal cancer.It increased the invasive and metastatic potential of tumor by altering a tumor microenvironment.TGFβ1 may be used as a possible biomarke.     

Gene transfer of somatostatin receptor type 2 by intratumoral injection inhibits established pancreatic carcinoma xenografts

AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmx5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group Ⅰ served as untreated control group. Group Ⅱ received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group Ⅲ received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group Ⅲ (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cms, and 1.412±0.146 g, respectively) and group Ⅱ (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P<0.05) The AI in group Ⅲ (1.47±0.13%) was significantly higher than that in groupⅠ(0.56±0.09%) and group Ⅱ (0.57±0.11%) (P<0.05). But there were no significant differences between groups Ⅰ and Ⅱ. CONCLUSION: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer.     

Preventing prolonged post-operative ileus in gastric cancer patients undergoing gastrectomy and intra-peritoneal chemotherapy

AIM: To assess the efficacy of metoclopramide (Met) for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy (IPC). METHODS: Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups. Sixteen patients received Met immediately after operation (group A), and 16 did not (group B). Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group (group C). All patients had received epidural pain control. The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort. Secondary endpoints were early complications during hospitalization. RESULTS: Gender, the type of resection, operating time, blood loss, tumor status and amount of narcotics were comparable in the three groups. However, the group C patients were older than those in groups A and B (67.5±17.7 vs 56.8±13.2,57.5±11.7 years, P= 0.048). First bowel flatus occurred after 4.35±0.93 d in group A, 4.94±1.37 d in group B, and 4.71±1.22 d in group C (P>0.05). Oral feeding of a soft diet was tolerated 7.21±1.92 d after operation in group A, 10.15±2.17 d in group B, and 7.53±1.35 d in group C (groups A and C vs group B, P<0.05). There was no significant difference in respect to the first flatus among the three groups. However, the time of tolerating oral intake with soft food in groups A and C patients was significantly shorter than that in group B patients. Levels of C-reactive protein (CRP) were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC. The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus. There was no increased risk of anastomotic leakage in patients receiving Met. CONCLUSION: The results suggest that a combination of intravenous Met and epidural pain control may be required to achieve a considerable decrease in time to resumption of oral soft diet in advanced gastric cancer patients who underwent gastrectomy and IPC. Furthermore, the administration of Met did not increase anastomotic leakage. Met has a role in the prevention of prolonged post-operative ileus.     

Anti-tumor activity of tanshinone ⅡA in combined with cyclophosphamide against Lewis mice with lung cancer

Objective:To explore the anti-tumor activity of tanshinone ⅡA in combined with cyclophosphamide against Lewis mice with lung cancer and the effect on cellular immune function.Methods:Lewis tumor cells were inoculated suhcutaneously into the right armpit of mice in each group(n=20) to establish Lewis lung cancer mice model.After model establishment,mice in the model group were given normal saline by lavage,qd.Mice in treatment Ⅰ group were given intraperitoneal injection of TanIIA,15 mg/kg,qd.Mice in treatment Ⅱ group were given intraperitoneal injection of CTX,25 mg/kg,qd.Mice in treatment Ⅲ group were given intraperitoneal injections of TanIIA and CTX,in which the administration method of TanIIA was the same as in treatment Ⅰ group,continuously for 2 weeks,and the dosage of CTX was the same as in treatment Ⅱ group,24 h after model establishment,every other day.Mice were sacrificed 2 weeks after establishment.The tumor tissues were collected to calculate the anti-tumor rate.Immunohistochemistry was used to detect the expressions of Bcl-2,Bax,VEGF,Angiostatin,and Endostatin.FCM was used to detect T lymphocyte subsets in spleen and liver of mice.Results:The tumor weight in treatment Ⅰ,Ⅱ,and Ⅲ groups was significantly lower than that in the model group(P0.05).The tumor weight in treatment Ⅲ group was significantly lower than that in treatment Ⅰ and Ⅱ groups(P0.05).The anti-tumor rate in treatment Ⅱ and Ⅲ groups was significantly higher than that in treatment Ⅰ group(P0.05).Bcl-2 expression in the tumor tissues of treatment Ⅰ,Ⅱ,and Ⅲgroups was significantly lower than that in the model group(P0.05),while Bax expression was significantly higher than that in the model group(P0.05).Bcl-2 expression in the tumor tissues of treatment Ⅰ and Ⅱ groups was significantly higher than that in treatment Ⅲ group(P0.05),while Bax expression was significantly lower than that in treatment Ⅲ group(P0.05).CD4~+ and CD4~+/CD8~+ in treatment Ⅰ,Ⅱ,and Ⅲ groups were significantly higher than those in the model group(P0.05).CD4~+ in treatment Ⅲ group was significantly higher than that in treatment Ⅰ and Ⅱ groups(P0.05),while CD4~+/CD8~+ was significantly higher than that in treatment Ⅱ group(P0.05).The comparison of CD8~+ among each group was not statistically significant(P0.05).NK cell activity in treatment Ⅰ,Ⅱ,and Ⅲ groups was significantly higher than that in the model group(P0.05).NK cell activity in treatment Ⅲ group was significantly higher than that in treatment Ⅰ and Ⅱ groups(P0.05).Conclusions:TannA in combined with CTX can down regulate Bcl-2 expression in lung cancer tissues,up regulate Bax expression,inhibit the neovascularization of tumor tissues,and enhance the immunological function,with a significant anti-tumor activity.     

Effects of augmentation of liver regeneration recombinant plasmid on rat hepatic fibrosis

AIM: To investigate the effects of eukaryotic expression of plasmid on augmentation of liver regeneration (ALR) in rat hepatic fibrosis and to explore their mechanisms. METHODS: Ten rats were randomly selected from 50 Wistar rats as normal control group. The rest were administered intraperitoneally with porcine serum twice weekly. After 8 wk, they were randomly divided into: model control group, colchicine group (Col), first ALR group (ALR1), second ALR group (ALR2). Then colchicine ALR recombinant plasmid were used to treat them respectively. At the end of the 4th wk, rats were killed. Serum indicators were detected and histopathological changes were graded. Expression of type Ⅰ, Ⅲ, collagen and TIMP-1 were detected by immunohisto-chemistry and expression of TIMP-1 mRNA was detected by semi-quantified RT-PCR. RESULTS: The histologic examination showed that the degree of the rat hepatic fibrosis in two ALR groups was lower than those in model control group. Compared with model group, ALR significantly reduced the serum levels of ALT, AST, HA, LN, PCIII and IV (P<0.05). Immunohistochemical staining showed that expression of type Ⅰ, Ⅲ, collagen and TIMP-1 in two ALR groups was ameliorated dramatically compared with model group (I collagen: 6.94±1.42,5.80±1.66 and 10.83±3.58 in ALR1, ALR2 and model groups, respectively; Ⅲ collagen: 7.18±1.95, 4.50±1.67 and 10.25±2.61, respectively; TIMP-1: 0.39±0.05,0.20±0.06 and 0.53±0.12, respectively,P<0.05 or P<0.01). The expression level of TIMP-1 mRNA in the liver tissues was markedly decreased in two ALR groups compared with model group (TIMP-1 mRNA/β-actin: 0.89±0.08, 0.65±0.11 and 1.36±0.11 in ALR1, ALR2 and model groups respectively, P<0.01). CONCLUSION: ALR recombinant plasmid has beneficial effects on rat hepatic fibrosis by enhancing regeneration of injured liver cells and inhibiting TIMP-1 expressions.     

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.     

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.     

Effects of N-acetylcysteine on expression of transforming growth factor-β1 in diabetic nephropathy rats

Objective To investigate the effects of N-acetylcysteine (NAC) on the expression of transforming growth factor-β1 (TGF-β1) in renal cortex of diabetic nephropathy rats.Methods A rat model of DN was established.The rats were randomly divided into control group,DN group and NAC group.After 8 weeks treatment,urinary albumin excretion rate (UAER) was determined.The expression of TGF-β1 in renal cortex was detected by immunohistochemistry and RT-PCR analysis.Pathomorphological changes of renal cortex were observed.Results (1)The levels of UA ER were significantly higher in DN group and NAC group [(1268.3±297.5) μg/24 h and (315.9-±86.8) μg/24 h] than in control group [(31.2±8.9) μg/24 h,q-29.85,16.76,both P＜0.01].The groups of DN and NAC versus group of control showed the increased levels of activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:7.35±1.17 and 3.87 ± 0.71 vs.1.95±0.34,q= 10.75,5.82,both P＜0.01];immune-histochemistry index of renal tubulointerstitium [21.21± 3.78 and 10.67±1.86 vs.3.62±0.79,q=15.20,11.36,both P＜0.01];the expression of mRNA in renal cortex[0.72±0.06 and 0.45±0.05 vs.0.23±0.04,q=9.13,7.45,both P＜0.01].The pathomorphological changes were significant in DN group and NAC group.(2)The NAC group versus DN group showed a decreased levels of UAER (q=8.17,P＜0.01),activity of TGF-β1 in renal cortex [immune-histochemistry index of glomerular mesangial area:q= 4.97,P＜0.01]immune-histochemistry index of renal tubulointerstitium (q = 6.86,P ＜ 0.01 );the expression of mRNA in renal cortex (q= 3.69,P＜0.05) and showed improvement of pathomorphology in renal cortex.(3) There was a significantly positive correlation between expression quantity of TGF-β1 mRNA in renal cortex and UAER level in NAC group(r= 0.749,P＜0.05).Conclusions The protective effects of NAC on the kidney of DN rats may be partly related with inhibition on the expression of TGF-β1.     

非小细胞肺癌患者呼出气冷凝液中p53蛋白检测的临床意义

Objective To study the clinical significance of the detection of p53 protein in exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC). Methods EBC and plasma of 98 patients with NSCLC were collected,p53 protein expression in EBC and plasma was detected by enzyme-linked immunosorbent assay,and the data were compared with those of 98 healthy controls. p53 protein expression in cancer tissue of 98 patients with NSCLC was detected by immunohistochemistry. p53 protein expression in EBC and plasma and positive expression rate of p53 protein in cancer tissue were compared among patients with different lung cancer type,stage,histologic type,tumor size,and lymph node metastasis,smoking history. The specificity and sensitivity of diagnosis of p53 protein in patients with NSCLC were analyzed by ROC curve. Results ① The level of p53 protein in EBC of patients with NSCLC was significantly higher than that in healthy control group [(233.99±7.91) ng/L vs ( 130. 26 ± 4. 73) ng/L,P ＜0. 01]. The level of p53 protein in serum of patients with NSCI.C was significantly higher than that in healthy control group [(292. 58 ± 8. 79) ng/L vs (141. 66±3. 33) ng/L,P ＜0. 01]. ② The level of p53 protein in EBC of patients with central lung cancer was higher than that in patients with peripheral lung cancer [(248. 22 ± 8. 58) ng/L vs (215. 78 ± 6.61) ng/L,P＜0. 01]. ③The level of p53 protein in EBC of patients with positive immunostaining group was higher than that in negative group [(249.77 ± 8.07) ng/L vs (216.86 ± 7.44) ng/L,P ＜ 0. 05]. ④The level of p53 protein in serum of smokers was significantly higher than that in non-smokers [(310.18 ± 9.04) ng/L vs (254. 55 ± 6. 91) ng/L,P ＜0. 01]. ⑤The positive expression rate of p53 protein in cancer tissue was 47. 96% (47/98). ⑥The sensitivity and specificity of diagnosis of p53 protein were 95. 90% and 90. 04% in plasma,and those were 92. 90% and 79. 59% in EBC. The cut off values of p53 protein were respectively 175. 68 ng/L and 166. 26 ng/L in EBC and serum. Conclusions The detection of p53 protein in EBC of patients with NSCLC is helpful for the diagnosis of lung cancer.     

Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-α

AIM: To investigate the effect of Boschniakia rossica (BR), oxymatrine (OM) and interferon-alpha (IFN-α) lb on the therapy of rat liver fibrosis and its mechanism. METHODS: By establishing a rat model of pig serum-induced liver fibrosis, liver/weight index and serum alanine transaminase (ALT) were observed to investigate the therapeutic effect of BR, OM and IFN-α Radioimmunoassay was utilized to measure procollagen type Ⅲ (PCⅢ) and collagen type Ⅳ (CⅣ). RT-PCR was used to assay the expression of liver transforming growth factor- beta 1 (TGF-β1) mRNA. Immunohistochemistry of alpha-smooth muscle actin (α-SMA) and pathologic changes of liver tissues were also under investigation. RESULTS: Serum PCⅢ and CⅣ in BR, OM and IFN-α groups were significantly declined compared with those in model group, and their RT-PCR revealed that TGF-β1 mRNA expression was also reduced more than that in model group. Immunohistochemistry demonstrated that α-SMA also declined more than that in model group. Serum ALT in IFN-α, control and model groups was within normal level. Serum ALT in BR group had no significant difference from those of IFN-α, control and model groups. Serum ALT in ON group was significantly higher than those in BR, IFN-α,model, and control groups. CONCLUSION: BR, OM and IFN-α can prevent pig serum-induced liver rat fibrosis by inhibiting the activation of hepatic stellate cells and synthesizing collagen. OM has hepatotoxicity to rat liver fibrosis induced by pig serum.     

Effect of Fuzheng Yiliu decoction combined with chemotherapy on patients with intermediate and late stage gastrointestinal cancer

AIM: To investigate the therapeutic effects of Fuzheng Yiliu (strengthening the body resistance to inhibit tumor) decoction combined with chemotherapy on the patients with intermediate and late stage gastrointestinal cancer. METHODS: Sixty patients were randomly divided into treatment group (chemotherapy combined with Fuzheng Yiliu decoction) and control group (chemotherapy alone). Four indexes, including the tumor recent remission rate (RR), the change of main symptoms, the toxic and side effects caused by chemotherapy and the change of performance status, were observed in the patients. Peripheral blood contents of CD3+, CD4+, CD8+ cells, CD4+/CD8+ and soluble interleukin-2 receptor (sIL-2R) were tested before and after treatment and the values were compared with those of healthy peoples. RESULTS: The improving rate of main symptoms (69.6%) and performance status (56.7%) were significantly higher in the treatment group than in the control group (34.8%, 26.7%, P<0.05). The occurrence rates of grade II toxic and side-effects on both bone marrow (13.3%) and digestive tract (30%) were lower in the treatment group compared to the control group (36.7%, 63.3%, P<0.05). Before treatment, the proportion of CD3+, CD4+ and CD4+/CD8+ decreased and the proportion of CD8+ and SIL-2R raised markedly both in the control group and treatment group as compared to the healttiy people. After treatment, that increased of CD3+, CD4+, CD4+/CD8+ increased (62.25±10.01% vs 68.31±9.72%, 36.83±10.44% vs 42.6±9.62%, 1.24±0.65 vs l.66±0.85, P<0.05) and the values of CD8+ and sIL-2R decreased obviously (33.06±7.69% vs 29.24±6.25%, 588.23±216.86 U/mL vs 475.87±211.36 U/mL,P<0.05) in the treatment group, whereas these values were opposite in the control group (64.22±6.91% vs60.63±5.75%,35.62±7.49% vs31.53±5.53%, 32.95±8.28% vs 37.14±7.48%, 1.17±0.43 vs 0.94±0.43, 573.63±214.32 U/mL vs 692.17?21.33 U/mL, P<0.05). CONCLUSION: Fuzheng Yiliu decoction can enhance therapeutic effects of chemotherapy on malignant gastrointestinal tumor, and also reduce the toxic and side effects on bone marrow and digestive tract, thereby improving the quality of life and cellular immunity in patients with malignant gastrointestinal tumor.     

Effect of moxibustion on prevention and treatment of nausea and vomiting caused by cisplatin in lung cancer

正Objective To observe the clinical effects between moxibustion combined with 5-hydroxy tryptamine (5-HT) receptor antagonist and simple 5-HT receptor antagonist in the prevention and treatment of nausea and vomiting caused by cisplatin chemotherapy in patients with lung cancer.Methods Fifty-eight patients with lung cancer treated with cisplatin chemotherapy were randomly assigned into an observation group and a control group,29 cases in each one. The patients in the two groups were applied by 5-HT receptor antagonist to prevent nausea and vomiting on the 1st three days of chemotherapy.     

Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

AIM: To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma (ESCC). METHODS: Beta-catenin mRNA expression level in 40 ESCC patients (28 males and 12 females, age range 38-82 years, median 60 years) was analyzed by real- time PCR. Beta-catenin mRNA expression levels in tumor cells were categorized as weaker (level 1) or equal to or stronger (level 2) than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS: Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis (0.0776 ± 0.0369 vs 0.3413 ± 0.1803, P < 0.001) and deeper tumor invasion (0.0751 ± 0.0356 vs 0.3667 ± 0.1928, P < 0.001), and a poorer survival rate (P = 0.0024) than ESCC with level 1 expression. CONCLUSION: Beta-catenin expression in ESCC is of great importance.     

Transforming growth factor-β and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma

AIM To understand the cellular and molecular changes inperipheral blood that can lead to the development of hepatocellular carcinoma(HCC) and provide new methods for its diagnosis and treatment.METHODS Peripheral blood mononuclear cells were isolated from the peripheral blood of HCC patients and normal controls and then analyzed by flow cytometry. The percentage of transforming growth factor-β(TGF-β)+ regulatory cells(Tregs) in the peripheral blood was measured, and the expression of TGF-β was also determined. Then, the relationship between the changes and the 5-year survival of patients was analyzed. In addition, recombinant human TGF-β(rh TGF-β) and recombinant human interleukin-6 were added to stimulate the cultured cells, and their effects on HCC were evaluated.RESULTS The expression of TGF-β and the percentage of TGF-β+ Tregs in the peripheral blood of HCC patients increased significantly compared with normal controls. Compared with the low TGF-β expression group, the high TGF-β expression group had a significantly lower 5-year survival rate, and the same result was found in the two TGF-β+ Treg groups, suggesting that TGF-β and TGF-β+ Tregs were negatively correlated with the overall survival of the patients. In addition, rh TGF-β promoted the growth of tumor cells and induced high expression levels of IL-6, which further promoted tumor proliferation.CONCLUSION The results showed that TGF-β may promote tumor growth and proliferation by inducing the production of IL-6, and TGF-β and TGF-β+ Tregs may serve as new markers for predicting a poor prognosis in HCC.     

Association of CT perfusion imaging with plasma levels of TGF-β1 and VEGF in patients with NSCLC

Objective: To study the association of CT perfusion imaging parameters with plasma level of transforming growth factor-β1(TGF-β1) and vascular endothelial growth(VEGF) in patients with non small cell cancer(NSCLC). Methods: A total of 67 patients with NSCLC(NSCLC group) and 64 patients with benign lesion(control group) were given with CT perfusion imaging to obtain blood flow, blood volume, mean transit time, time to peal and permeability surface through CT perfusion software. The plasma levels of TGF-β1 and VEGF were tested by ELISA. The relationship between plasma levels of TGF-β1, VEGF and CT perfusion imaging parameters were analyzed. Results: CT perfusion imaging parameters and the plasma levels of TGF-β1 and VEGF of NSCLC group were significantly higher than the control group(P0.05), while CT perfusion parameters and the levels of TGF-β1 and VEGF in NSCLC group showed significant difference in different tumor node metastasis stages(P0.05). Correlation analysis showed that the level of plasma TGF-β1 and VEGF were positively correlated with blood flow, blood volume, and mean transit time(P0.05), and negatively correlated with time to peal(P0.05). There was no significant correlation between TGF-β1 and VEGF with the permeability surface. Conclusions: CT perfusion imaging parameters in patients with NSCLC is closely associated with plasma TGF-β1, VEGF and its biological characteristics. CT perfusion imaging is a convenient method to detect tumor blood perfusion.