Decreased blood riboflavin levels are correlated with defective expression of RFT2 gene in gastric cancer

AIM: To investigate the relationship between blood riboflavin levels and riboflavin transporter 2 (RFT2) gene expression in gastric carcinoma (GC) development.METHODS: High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC. Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue.RESULTS: A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane (0.398 ± 0.149 vs 1.479 ± 0.587; P = 0.040). Tumors exhibited low RFT2 protein expression (75%, 16.7%, 8.3% and 0% for no RFT2 staining, weak staining, medium staining and strong staining, respectively), which was significantly lower than that in the normal mucous membrane (10%, 16.7%, 26.7% and 46.7% for no RFT2 staining, weak staining, medium staining and strong staining, respectively; P < 0.05). Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade. Moreover, a significantly decrease in Uyghur patients was observed compared with Han patients. However, other parameters-gender, tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression. Blood riboflavin levels were reverse correlated with development of GC (1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients; P < 0.05). A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients (χ² = 2.619; P = 0.019).CONCLUSION: Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC.     

新疆不同民族食管癌血浆代谢组学差异分析

Objective To investigate the metabonomic variation between patients with esophageal cancer (EC) and healthy controls, and to analyze the variation between patients with EC. Methods 1H-MR and orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed on 108 plasma specimens from EC patients and 50 health controls, and the metabonomic variation between patients with EC and healthy controls analyzed. Results OPLS-DA analysis might correctly separate all plasma specimens from health controls and patients with EC ,leucine(0. 0043±0. 0006,0. 0040±0. 0006) ,alanine(0. 0039±0. 0007,0. 0033±0. 0006), isoleucine (0. 0067±0. 0010,0. 0063±0. 0009), valine (0. 0037±0. 0005,0. 0035±0. 0006) ,glycopretein(0. 0123±0. 0043,0. 0102±0. 0022), lactate(0. 0342±0. 0113,0. 0258±0. 0085), acetone (0. 0027±0. 0023,0. 0017±0. 0008), acetate (0. 0007±0. 0001,0. 0006±0. 0001),choline(0.0035±0.0006, 0.0029±0.0007), isobutyrate (0.0020±0.0004, 0.0018±0.0003),unsaturated lipid (0. 0072±0. 0013,0. 0059 + 0. 0018), VLDL (0. 1209±0. 0589,0. 0879±0. 0269), LDL (0. 0885±0. 0328,0. 0785±0. 0288), 1-methylhistidine(O. 0005±0. 0001,0. 0004±0. 0005)decreased in EC patient' s plasma with statistical significance (r total>0. 27, P<0. 05), dimethylamine (0. 0004±0. 0001,0. 0005±0. 0001), α-glucose (0. 0079±0. 0013,0. 0081±0. 0016), β-glucose (0. O139±0. 0024,0. 0142±0. 0029) ,citric acid (0. 0044±0. 0008,0. 0106±0. 0058) increase in the EC patient's plasma (r total<-0. 27 ,P<0. 05). There were clear variation between Han and Kazak patients,alanine(0. 0031±0. 0005,0. 0029±0. 0004), glutamine (0. 0010±0. 0001,0. 0009±0. 0001), tyrosine (0. 0009±0. 0001,0. 0008±0. 0001), 1-methylhistidine (0. 0005±O. 0001,0. 0004±0. 0001) increased in the Han patients (r>0. 35, P>0. 05), carnitine (0. 0028±0. 0006) was higher in Kazak patients than in Han patients (0. 0025±0. 0004), which had statistical siginificance (r=-0. 40, P<0. 05). Unsaturated lipid (0. 0059±0. 0018,0. 0047±0. 0011), isoleucine (0. 0062±0. 0011,0.13058±0. 0007), alanine (0.0032±0. 0007, 0. 0028±0. 0004) ,glycoprotein (0. 0096±0. 0019,0. 0086±0. 0011) ,glutamine (0. 0011±0. 0001,0. 01309±0. 0001) ,tyrosine(0. 0009±0. 0001, 0. 0008±0. 0001), 1-methylhistidine (0. 0005±0. 0001, 0. 0004±0. 0001)were increased in Uygnr patients as compared with Kazak patients, having statistical significance (r>0. 33 ,P<0. 05), carnifine (0. 0027±0. 0005) was higher in Kazak patients than in Uygur patients (0.0025±0.0004)(r=-0.36,P<0.05). Conclusion The results indicate that1H-MR spectra of plasma analyzed by OPLS-DA statistical methods might completely separate the EC patients from health controls. The metabonomic approach should be helpful in screening of EC patients.     

HPV16与新疆维吾尔族食管鳞癌的相关性

目的:调查新疆维吾尔族食管鳞癌患者中人乳头瘤状病毒(HPV)16型的感染率.方法:采用PCR技术检测82例新疆维吾尔族食管鳞癌和80例癌旁正常食管黏膜石蜡包埋组织HPV16的感染率,分析其与新疆维吾尔族食管鳞癌发生的关联性.结果:在新疆维吾尔族食管鳞癌组织中,HPV16型检出率为31.7%(26/82),与对照组12.5%(10/80)相比,差异有统计学意义(X2=8.643,P<0.05);按照年龄、性别、病理分化程度及临床分期对维吾尔族食管鳞癌中的HPV16感染状况比较,差异均无统计学意义(X2=0.301、0.149、2.876、0.105,均P>0.05).结论:HPV16型感染与新疆维吾尔族食管鳞癌的发生存在一定的相关性,但与患者的年龄、性别、病理分化程度及临床分期无明显的关联性.     

新疆伊犁地区食管鳞癌与儿茶酚-O-甲基转移酶基因Val158Met多态性的关联分析

目的 探讨儿茶酚-O-甲基转移酶(COMT)基因缬氨酸(Val)158甲硫氨酸(Met)(G→A转换)多态性在新疆伊犁地区人群中的分布及与食管鳞癌(ESCC)的关系.方法 采用以医院为基础的病例对照研究方法,研究对象共622名,包括214例ESCC患者,408名年龄、性别、民族相匹配的正常对照.以聚合酶链反应-限制性片段长度多态性方法分析COMT基因G/A多态性.结果 622名受试者COMT基因型频率分布依次为GG型占47.3%,GA型占42.3%,AA型占10.4%;等位基因G为68.4%,A为31.6%.食管癌组与正常对照组COMT基因型及等位基因频率分布差异无统计学意义(P＞0.05).分层分析显示,年龄≤60岁的食管癌组与正常对照组之间COMT基因型(x2=6.101)和等位基因频率(x2=4.493)差异有统计学意义(P值均＜0.05);哈萨克族、维吾尔族、汉族ESCC组间等位基因频率比较差异有统计学意义(x2=6.671,P＜0.05);三个民族正常对照组间COMT基因型(x2=13.567)及等位基因频率(x2=11.321)分布比较差异均有统计学意义(P值均＜0.05).将年龄及性别校正后,新疆伊犁地区食管癌组与正常对照组COMTVal158Met多态性在哈萨克族、维吾尔族、汉族之间差异均无统计学意义.结论 COMT基因Val158Met单核苷酸多态可能不是新疆伊犁地区食管鳞癌危险性的遗传标志.

Abstract：

Objective To explore the relationship between polymorphism of catechol-O-methyltransferase (COMT) gene valine (Val) 158 methionine (Met) (G to A transition)and the distribution in population and esophageal squamous cell carcinoma (ESCC) in Yili prefecture of Xinjiang.Methods A hospital based case-control study was adopted, a total of 622 subjects, which including 214 ESCC patients and 408 age, gender and ethnicity-matched normal control individuals.The polymorphism of COMT gene G to A transition was analyzed with PCR-restriction fragment length polymorphism approaches.Results The COMT genotype frequencies in 622 subjects in Yili prefecture were GG genotype accounted for 47.3%, GA type for 42.3% and AA type for 10.4%, G allele was 68.4% and A allele was 31.6%.There was no statistical difference in the COMT genotype and frequencies of allele distribution between ESCC group and control group.Furthermore, stratified analysis indicated that there was statistical difference between ESCC group and control group in subjects less than 60 years old.There was statistical difference in the allele distribution among Kazak,Uygur and Han ESCC groups.The COMT genotype and frequency of allele distribution among normal control groups of the three ethnic groups were statistically different.After corrected age and gender,there was no statistical difference in COMT Val158Met polymorphisms among Kazakh, Uygur and Han ethnic groups in both ESCC and control groups in Yili Prefecture of Xinjiang.Conclusion COMT gene Val158Met single nucleotide polymorphism may not be the genetic markers of ESCC risk in Yili Prefecture of Xinjiang.     

MiR-106b promotes migration and invasion through enhancing EMT via downregulation of Smad 7 in Kazakh’s esophageal squamous cell carcinoma

Tumor Biology - Accumulated evidence suggests that miR-106b played a key role in the promotion of the metastases of cancer; however, little is known about miR-106b in esophageal squamous cell...     

哈萨克族食管癌患者组织中细胞外信号调节激酶/丝裂原活化蛋白激酶信号通路的表达

目的 探讨细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MAPK)信号通路在哈萨克族食管鳞癌患者组织中的表达变化及意义.方法 采用Western blot技术检测在血清饥饿条件下、U0126梯度浓度处理下,食管癌细胞系EC9706中磷酸化ERK1(p-ERK1)和磷酸化ERK2(p-ERK2)的表达变化.采用实时荧光定量PCR法检测25例哈萨克族食管癌患者肿瘤组织和癌旁正常组织中总ERK1(t-ERK1)和总ERK2(t-ERK2)mRNA的表达变化.采用Western blot技术检测25例哈萨克族食管癌患者肿瘤组织、癌旁正常组织以及5例哈萨克族非食管癌者正常食管组织中t-ERK1、t-ERK2、p-ERK1和p-ERK2蛋白的表达变化.采用免疫组化染色法,在126例石蜡包埋标本(正常食管黏膜19例,食管原位癌55例,食管浸润癌52例)中验证p-ERK1和p-ERK2蛋白的表达变化.结果 在食管癌EC9706细胞中,ERK/MAPK信号通路呈高度活化状态.血清瞬时刺激10 min后,p-ERK1和p-ERK2的表达达到峰值.EC9706细胞在50 μmol/L的U0126处理下,p-ERK1和p-ERK2的表达几乎完全被抑制.t-ERK1 mRNA在25例哈萨克族食管癌患者肿瘤组织中的表达量为1.92±3.49,明显低于癌旁组织(3.67±7.47,P<0.05);t-ERK2 mRNA在食管癌组织和癌旁组织中的表达量差异无统计学意义(P>0.05).t-ERK1和t-ERK2蛋白在食管癌组织、相应癌旁组织和正常食管黏膜组织中的表达差异无统计学意义(P>0.05);但p-ERK1和p-ERK2蛋白在食管癌组织中的表达量(分别为0.87±0.14和0.79±0.10)均明显低于癌旁组织(分别为1.10±0.13和1.32±0.12,P<0.05)和正常食管黏膜组织(分别为1.50±0.22和1.64±0.18,P<0.05).免疫组化染色验证的结果 显示,p-ERK1和p-ERK2蛋白在浸润性食管癌组织中的阳性表达率均为7.7%(4/52),在癌旁正常食管黏膜组织中的阳性表达率均为31.6%(6/19),在食管原位癌组织中的阳性表达率均为85.5%(47/55),不同组织间的表达差异有统计学意义(P<0.05).结论 在食管癌细胞中,ERK/MAPK信号通路呈活化状态.ERK/MAPK信号通路活化水平的改变可能参与了哈萨克族食管癌患者肿瘤的早期发生.

Abstract：

Objective To investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients. Methods The expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas. Results ERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 μmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92±3.49 in the ESCC tissues and 3.67±7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P<0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P>0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87±0.14 and 0.79±0.10 in the ESCC tissues, and 1.10±0.13 and 1.32±0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P<0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P>0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P<0.05). Conclusions ERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.     

家兔食管粘膜下肿瘤光动力学诊断的实验研究

目的　探讨利用光敏剂单天门冬酰胺二氢卟酚e6 (NPe6 )的长波长区吸光谱对较深部食管肿瘤作光动力学诊断的可能性 ,以及NPe6的理想剂量和照光时间。方法　雄性日本纯种白兔 12只 ,在全麻下开腹 ,将VX2肿瘤细胞混悬液 (5× 10 6细胞 /ml) 0 1ml种植于食管粘膜下。 1周后将家兔随机分成 4组 (每组 3只 ) ,1组作为对照组 ,其余 3组分别按 1 0、2 5和 5 0mg/kg耳缘静脉注射NPe6 ,给药后 2、4、6和8h用半导体激光内镜荧光观测系统对食管粘膜下肿瘤及周围正常组织中的NPe6荧光进行观察 ,并计算肿瘤组织 /正常组织相对荧光强度 (T/N)比值。结果　各给药组家兔给药后不同时间在食管肿瘤部位发射出较强的NPe6荧光 ,与邻近正常食管呈鲜明对照。食管肿瘤与周围正常组织中NPe6荧光强度随给药后时间增加而减弱 ,但在给药后 2～ 6h ,T/N比值随时间增加而增大。 5 0mg/kg组T/N比值在给药后 4～ 8h明显高于其他 2组 (P <0 0 5 ) ,于 6h时显示最大值 (3 49± 0 32 )。而其他 2组间差异无显著意义 (P >0 0 5 )。对照组家兔的肿瘤及正常组织均未检测出荧光。结论　利用NPe6长波长区吸光谱 ,对较深部食管肿瘤作光动力学诊断是可行的 ,给药剂量为 5 0mg/kg、给药后 6h进行诊断较为适宜。     

Toxicity of Anthraquinones: Differential Effects of Rumex Seed Extracts on Rat Organ Weights and Biochemical and Haematological Parameters

The genus Rumex and related species such as Rheum and Polygonum are widely used as medicinal herbs and foods. They contain anthraquinones (AQ) such as emodin and chrysophanol as active ingredients, and there is concern about the toxicity of these compounds. This study evaluated the chronic effects of Rumex patientia seed aqueous and ethanolic extracts, in male and female rats separately, on organ weights and over 30 haematological, biochemical and histological parameters, immediately after 14‐week administration and after a further period of 15 days without drug treatment. Adverse changes were associated with long‐term AQ administration, and these focussed on the liver, lung and kidney, but after 15‐day convalescence, most had reverted to normal. In general, male rats appeared to be more susceptible than female rats at similar doses. The water extract produced no irreversible changes, which may reflect the lower dose of the AQ constituents or the presence of different ancillary compounds, and supports the traditional method of extracting Rumex seeds with water. In conclusion, ethanolic extracts of R. patientia caused irreversible pathological changes at very high doses (4000mg/kg), but lower doses and aqueous extracts produced either non‐significant or reversible changes. Long‐term administration of high doses of AQ extracts over a long period of time should be avoided until further assurances can be given, and given other existing reports of reproductive toxicity, should be avoided altogether during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.     

490例原发性支气管肺癌的外科治疗

目的总结490例原发性支气管肺癌的手术治疗经验.方法回顾分析本科自1978年1月～2003年1月间对490例不同民族肺癌患者手术治疗的临床病理资料和随访结果.结果全组手术切除448例,切除率为91.4%,其中全肺切除76例,肺叶切除372例.术后并发症发生率为10.4%,手术死亡率为0.8%.随访率为85.2%,术后1、3和5年生存率分别为88.1%、56.6%和42.3%.P-TNM分期、淋巴结状况、病理类型与预后有关(P＜0.05),而手术方式对预后无显著影响(P＞0.05).结论早期确诊是提高治疗效果的关键,手术治疗仍是治疗肺癌的首选方法,其次配合术后放疗、化疗.严格的围术期管理有助于防止术后并发症的发生.手术治疗的预后与肿瘤的P-TNM分期、病理类型和淋巴结转移有密切关系.