肺癌细胞中RASSF4的高表达抑制肺癌细胞的增殖和侵袭能力

目的:探讨RASSF4在肺癌中的增殖和侵袭能力。方法:向肺癌细胞系H460和A549中导入RASSF4的cDNA质粒后,通过MTT、克隆形成实验、基质胶侵袭实验、流式细胞术等方法检测肺癌细胞的生长和侵袭能力。结果:RASSF4能够通过下调MMP2、MMP9和cyclinD1的表达,抑制肺癌细胞的侵袭、增殖及克隆形成能力。结论:RASSF4在肺癌细胞中通过抑制细胞生长及侵袭能力发挥重要的肿瘤抑制功能。     

含铂双药对比非铂单药二线治疗晚期非小细胞肺癌的系统评价

目的系统评价联合铂类的双药方案和非铂类单药方案二线治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的有效性及安全性。方法计算机检索PubMed、The Cochrane Library、Web of science、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)和万方数据库,收集含铂双药化疗方案对比非铂单药化疗方案二线治疗晚期NSCLC的随机对照试验,用RevMan 5.2进行荟萃分析。结果最终纳入11项临床随机对照试验,共1 167例患者。Meta分析结果显示,与非铂单药方案相比,含铂双药方案化疗可提高晚期NSCLC患者的化疗客观有效率(overall response rate,ORR)及疾病控制率(disease control rate,DCR),分别为1.43倍(RR=1.43,95%CI为1.08~1.89,P=0.010)和1.16倍(RR=1.16,95%CI为1.05~1.27,P=0.002)。同时,含铂双药方案化疗亦可延长晚期NSCLC患者的无进展生存期(progression-free survival,PFS),HR=0.74,95%CI为0.58~0.95,P=0.020;但含铂双药化疗与非铂单药化疗组1年生存率差异无统计学意义,RR=1.21,95%CI为0.91~1.61,P=0.190。安全性方面,含铂双药方案化疗最主要的不良反应为血小板减少,RR=2.99,95%CI为1.95~4.59,P<0.001;而3~4级白细胞减少、中性粒细胞减少、恶心呕吐和贫血等不良反应,含铂双药化疗与非铂单药化疗组差异均无统计学意义。结论与非铂单药化疗方案相比,含铂双药方案可提高晚期NSCLC患者化疗ORR及DCR,延长晚期NSCLC患者的PFS,但不能明显改善1年生存率。最主要不良反应为血小板减少,低毒耐受性好。因此,含铂双药化疗方案在一线治疗失败的晚期NSCLC患者的二线治疗中值得进一步推广。     

沙利度胺改善恶性肿瘤患者围化疗期恶心、呕吐的临床研究

目的 探讨沙利度胺治疗恶性肿瘤患者围化疗期恶心、呕吐的临床疗效及不良反应.方法 70例患者随机分为治疗组（38例）和对照组（32例）.治疗组于化疗前1d晚睡前开始顿服沙利度胺,起始剂量第1周100 mg/d,如能耐受不良反应,每晚增加50 mg,直至按剂量200 mg/d维持,如不能耐受加量者,则维持原剂量,服用至围化疗期结束;同时化疗前30 min静脉注射托烷司琼2 mg.对照组于化疗前30min静脉注射托烷司琼2mg,评价两组的止吐效果及不良反应.结果 治疗组与对照组的呕吐控制有效率分别为89.5％（34/38）、68.8％（22/32）,差异有统计学意义（P＜0.05）;两组的不良反应类似,差异无统计学意义（P＞0.05）.结论 沙利度胺联合托烷司琼可有效改善恶性肿瘤患者围化疗期的呕吐,不良反应可耐受,进一步提高了沙利度胺临床抗肿瘤治疗的适应证.     

~（18）F-FDG SPECT/CT检查结合CA125检测在卵巢癌术后复发转移诊断中的价值

目的：探讨18F-FDG SPECT/CT检查结合CA125检测在卵巢癌术后复发病例的早期诊断价值。方法：对43例卵巢癌术后病例同时进行18F-FDG SPECT/CT检查和CA125检测,怀疑复发的病例进行CT/MRI检查和临床随访,以进一步确诊。结果：43例病人中,18F-FDG SPECT/CT检查发现核素异常浓聚24例,经CT/MRI检查和临床资料证实为转移灶19例,阳性率和假阳性率分别为44.2%、11.6%,特异性为83.8%。本组病例CA125升高13例,证实为转移灶病例中CA125升高12例,阳性率和假阳性率分别为27.9%、2.3%,特异性为96.9%。结论：18F-FDG SPECT/CT检查和CA125检测是卵巢癌术后复发的可靠检查方法。     

马钱子碱经皮给药对乳腺癌骨转移抑制机制的探讨

目的:探讨马钱子碱经皮给药对乳腺癌骨转移的抑制机制,为乳腺癌的治疗提供新的途径.方法:培养人乳腺癌细胞株MDA-MB-231,取对数生长期细胞制成单细胞悬液.20只雌性Balb/c-nu/nu裸鼠麻醉后,无菌条件下,局部骨内注射乳腺癌单细胞悬液0.2 mL,复制乳腺癌骨转移模型.20只荷瘤裸鼠随机分为马钱子碱高剂量组、中剂量组、低剂量组和模型组4组,分别给予20％(0.2 mg/g)、10％(0.1 mg/g)和5％(0.05 mg/g)浓度的马钱子碱膏(每日总剂量≤腹腔给药的半数致死量)和凡士林经皮给药,涂抹裸鼠的整个腹部和造模的部位,1 g/次,4次/d(每次间隔3 h),连续15 d.影像学观察骨转移情况;RT-PCR检测并比较各组肿瘤组织中,骨转移相关因子VEGF、COX-2和PTHrP的表达量.结果:胫骨的X射线表现,马钱子碱高剂量组和中剂量组的骨质破坏不明显,低剂量组和模型组的骨质破坏明显,甚至出现病理性骨折.RT-PCR结果显示,钱子碱高剂量组VEGF、COX-2和PTHrP mRNA的表达分别为25.30±0.90、20.63±0.73和25.56±0.54,马钱子碱中剂量组分别为24.10±0.73、20.49±0.76和25.74±0.48,马钱子碱低剂量组分别为25.27±0.75、21.02±0.65和25.65±0.44,模型组分别为24.09±0.74、21.14±0.66和25.75±0.39.与模型组比较,马钱子碱各剂量组VEGF、COX-2和PTHrP mRNA的表达量随着马钱子碱剂量的增加逐渐下降,差异均有统计学意义,P＜0.05.结论:马钱子碱经皮给药能抑制裸鼠乳腺癌骨转移瘤的生长,减轻骨损伤,其机制可能是通过调控VEGF、COX-2和PTHrP的表达而抑制乳腺癌骨转移瘤的生长.     

Pro-oncogenic function of HIP-55/Drebrin-like (DBNL) through Ser269/Thr291-phospho-sensor motifs

HIP-55 (HPK1-interacting protein of 55 kDa, also named DBNL, SH3P7, and mAbp1) is a multidomain adaptor protein that is critical for organ development and the immune response. Here, we report the coupling of HIP-55 to cell growth control through its 14-3-3-binding phospho-Ser/Thr-sensor sites. Using affinity chromatography, we found HIP-55 formed a complex with 14-3-3 proteins, revealing a new node in phospho-Ser/Thr-mediated signaling networks. In addition, we demonstrated that HIP-55 is required for proper cell growth control. Enforced HIP-55 expression promoted proliferation, colony formation, migration, and invasion of lung cancer cells while silencing of HIP-55 reversed these effects. Importantly, HIP-55 was found to be upregulated in lung cancer cell lines and in tumor tissues of lung cancer patients. Upregulated HIP-55 was required to promote the growth of tumors in a xenograft animal model. However, tumors with S269A/T291A-mutated HIP-55, which ablates 14-3-3 binding, exhibited significantly reduced sizes, supporting a vital role of the HIP-55/14-3-3 protein interaction node in transmitting oncogenic signals. Mechanistically, HIP-55-mediated tumorigenesis activity appears to be in part mediated by antagonizing the tumor suppressor function of HPK1. Thus, the HIP-55–mediated oncogenic pathway, through S269/T291, may be exploited for the development of new therapeutic strategies.     

Effects of ARHI on cell cycle progression and apoptosis levels of breast cancer cells

The purposes of this study were to investigate the role of Aplysia Ras Homolog I (ARHI) on cell growth, proliferation, apoptosis, and other biological characteristics of HER2-positive breast cancer cells. Our goal was to provide experimental evidence for the development of future effective treatments of HER2-positive breast cancer. A pcDNA3.1-ARHI eukaryotic expression vector was constructed and transfected into the human HER2-positive breast cancer cell lines SK-BR-3 and JIMT-1. Then, various experimental methods were utilized to analyze the biological characteristics of ARHI-expressing breast cancer cells and to examine the impact of expression of the ARHI gene on cyclin D1, p27^Kip1, and calpain1 expression. We further analyzed the cells in each group after treatment with trastuzumab to examine the effects of this drug on various cellular characteristics. When we compared pcDNA3.1-ARHI-expressing SK-BR-3 and JIMT-1 cells to their respective empty vector and control groups, we found that cell viability was significantly lower (p?<?0.05) in the ARHI-expressing cells, and the proportions of G1 phase cells and apoptotic cells were significantly higher in the ARHI-expressing cells (p?<?0.05). In all groups of SK-BR-3 cells, trastuzumab treatment significantly decreased cell growth (p?<?0.05). The proportion of cells in G1 phase and the number of apoptotic cells in the pcDNA3.1-ARHI-expressing group were significantly higher than that in the empty vector group and the control group (p?<?0.05). The growth of pcDNA3.1-ARHI-transfected JIMT-1 cells was significantly decreased (p?<?0.05), while the proportion of apoptotic cells was significantly increased (p?<?0.05). Cell growth, viability, and the percentage of apoptotic cells were similar between the JIMT-1 empty vector and control groups. ARHI expression inhibited cyclin D1 expression in SK-BR-3 cells and JIMT-1 cells, while it promoted p27^Kip1 and calpain1 expression in these cells. ARHI expression inhibits the growth and proliferation of HER2-positive breast cancer cells, while it also promotes apoptosis in these cells. ARHI expression also improves the sensitivity of JIMT-1 cells to trastuzumab by inducing apoptosis.     

Serum lipid levels and the risk of biliary tract cancers and biliary stones: A population-based study in China

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Gallstones, the predominant risk factor for biliary cancers, are linked with hyperlipidemia. As part of a population-based case-control study conducted in Shanghai, China, we examined the associations of serum lipid levels with biliary stones and cancers. We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile duct, and 55 ampulla of Vater), 981 biliary stone cases and 858 healthy individuals randomly selected from the population. Participants completed an in-person interview and gave overnight fasting blood samples. Participants in the highest quintile of triglycerides (>/=160 mg/dl) had a 1.4-fold risk of biliary stones (95% CI = 1.1-1.9), a 1.9-fold risk of gallbladder cancer (95% CI = 1.3-2.8), and a 4.8-fold risk of bile duct cancer (95% CI = 2.8-8.1), compared to the reference group (third quintile: 90-124 mg/dl). Participants in the lowest quintile of high-density lipoprotein (HDL) (<30 mg/dl) had a 4.2-fold risk of biliary stones (95% CI = 3.0-6.0), an 11.6-fold risk of gallbladder cancer (95% CI = 7.3-18.5), and a 16.8-fold risk of bile duct cancer (95% CI = 9.1-30.9), relative to the reference group (third quintile: 40-49 mg/dl). In addition, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A (apo A) were inversely associated with biliary stones; whereas low levels as well as high levels of total cholesterol, LDL, apo A and apolipoprotein B (apo B) were associated with excess risks of biliary tract cancers. Our findings support a role for serum lipids in gallstone development and biliary carcinogenesis.     

Evaluation of the Seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification

BACKGROUND:

The seventh TNM staging system for gastric cancer of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) had a more detailed classification than the sixth TNM staging system for both the tumor (T) and lymph nodes (N). The authors compared survival rates assessed by the seventh staging system with those by the sixth system.

METHODS:

The authors analyzed the prospectively collected database on patients with gastric cancer who underwent surgery at Seoul National University Hospital between 1986 and 2006, and calculated the survival rates of 9998 cases with primary cancer, R0 resection, and >14 retrieved lymph nodes.

RESULTS:

The 5‐year cumulative survival rates (5YSR) according to the seventh edition T or N classifications were significantly different. The 5YSR according to seventh edition of the TNM staging system were 95.1% (stage IA), 88.4% (stage IB), 84.0% (stage IIA), 71.7% (stage IIB), 58.4% (stage IIIA), 41.3% (stage IIIB), and 26.1% (stage IIIC), which were significantly different from each other. The 5YSR of the seventh edition T2 and T3 classifications had significant differences in patients with every N classification, and the 5YSR of seventh edition N1 and N2 classifications had significant differences in T2 patients, T3 patients, and T4 patients. Each stage in the sixth edition was divided into the seventh edition stage with different survival rates. In addition, the number of homogenous groupings in seventh edition TNM stages was increased from 1 to 2.

CONCLUSIONS:

The seventh system provided a more detailed classification of prognosis than the sixth system, especially between T2 and T3 tumors and N1 and N2 tumors, although further studies were found to be needed for the N3a and N3b classification. Cancer 2010. © 2010 American Cancer Society.     

应用生物发光技术研究甲基硒酸对L9981-Luc肺癌细胞株移植瘤模型生长转移的影响

背景与目的 甲基硒酸是一种新型的人工合成的硒化合物.研究发现甲基硒酸对肿瘤细胞的生长转移有抑制作用.本研究的目的是探讨甲基硒酸对L9981-Luc裸鼠异体移植瘤生长和转移能力的抑制作用及机制.方法 建立L9981-Luc肺癌细胞株移植瘤模型,用精诺真活体动物可见光成像系统观察肺癌移植瘤肿瘤生长转移情况.实验将6周龄裸鼠15只,随机分为3组,每组5只,对照组每日腹腔注射生理盐水0.2 mL;甲基硒酸组每日腹腔注射甲基硒酸溶液50μg (0.2mL);顺铂组每周腹腔注射顺铂4 mg/kg.结果 接种第21天,不同组间原发瘤发光值比较差异有统计学意义(P=0.002);顺铂组发光值明显低于对照组(P=0.001),甲基硒酸组发光值明显低于对照组(P=0.031).不同药物处理组胸部转移信号发光值差异无统计学意义(P＞0.05).结论甲基硒酸能明显抑制L9981-Luc裸鼠异体移植瘤生长,并有抑制L9981-Luc原发瘤肺转移的趋势.