Twist与Akt在恶性肿瘤中作用的研究进展

恶性肿瘤是目前危害人类健康最严重的疾病,同时也是生命科学研究的热点。近年来的研究发现,Twist及Akt均具有癌基因的特性,它们能通过多种途径抑制细胞凋亡,是肿瘤转移的必要基因,在肿瘤的形成、发展和转移过程中均发挥了重要的作用。本文就Twist及Akt与恶性肿瘤的相关性作一综述。     

Twist和基质金属蛋白酶-2在乳腺浸润性导管癌组织中的表达分析

目的 分析探讨Twist和基质金属蛋白酶(MMP)-2在乳腺浸润性导管癌组织中的表达及其与乳腺浸润性导管癌临床病理特征的关系.方法 采用免疫组织化学EliVision Plus法检测68例乳腺浸润性导管癌及20例乳腺纤维腺瘤组织中Twist和MMP-2的表达,并结合临床病理特点进行分析.结果 Twist、MMP-2在乳腺浸润性导管癌组织中的阳性表达率分别为56%、74%,明显高于乳腺纤维腺瘤中的表达率15%和35%,差异有统计学意义(P<0.01).Twist、MMP-2蛋白在乳腺浸润性导管癌中阳性表达率为55.88%、73.53%,明显高于其在乳腺纤维腺瘤中阳性表达率15%、35%,差异有统计学意义(χ2值分别为10.380和10.055,P<0.01).乳腺浸润性导管癌组织中Twist与MMP-2的阳性表达呈正相关(r=0.272,P<0.05).结论 乳腺浸润性导管癌组织中Twist和MMP-2呈高表达,且两者呈正相关,联合检测Twist和MMP-2在乳腺浸润性导管癌中的阳性表达,有助于判断乳腺浸润性导管癌的淋巴结转移潜能.     

siRNA沉默Twist基因对鼻咽癌细胞CNE-2增殖的影响

目的探讨RNA干扰沉默Twist基因对人鼻咽癌细胞株CNE-2的迁移、侵袭和增殖等生物学活性的影响。方法构建Twist-shRNA表达载体,脂质体法将重组质粒分别转染入鼻咽癌细胞株CNE-2中,RT-PCR法检测Twist mRNA、Western blot法检测Twist蛋白表达量的变化。MTT法检测细胞的增殖,细胞创伤愈合试验观察细胞迁移能力,Tran-swell小室试验检测细胞侵袭能力的变化。结果沉默Twist基因可减慢CNE-2细胞生长速度(与对照组比较P<0.05),降低CNE-2细胞的迁移速度,抑制CNE-2的体外侵袭能力。结论靶向封闭Twist基因的表达,可明显抑制CNE-2细胞的增殖、迁移及侵袭能力,提示Twist可作为鼻咽癌防治的一个新的靶点。     

Twist在肝细胞癌组织中的表达及临床意义

目的:探讨Twist在肝细胞癌中的表达意义及其与缺氧诱导因子-1α(HIF-1α)的关系。方法:采用免疫组化方法分别检测89例肝细胞癌组织中Twist和HIF-1α的表达状况,并分析其与临床病理间的关系。结果:癌组织Twist的阳性表达率为70.79%,明显高于癌旁组织19.10%(P<0.05)。Twist和HIF-1α的表达呈正相关(P<0.05),与HCC病理分级呈正相关(P<0.05)。结论:肝细胞癌组织与癌旁组织在Twist高表达率上存在明显差异,在肝细胞癌发生、发展过程中它可能与HIF-1α信号通路有直接作用,检测Twist表达对预后判断有一定帮助。     

前列腺癌组织中Twist和缺氧诱导因子-1α的表达及意义

目的探讨Twist和缺氧诱导因子-1α（HIF-1α）在前列腺癌组织中的表达及意义。方法应用免疫组化（EnVision）法分别检测30例前列腺增生组织、30例前列腺上皮内瘤变组织及70例前列腺癌组织Twist、HIF-1α蛋白表达情况。结果①Twist、HIF-1α在前列腺增生组织、前列腺上皮内瘤变组织及前列腺癌组织中的阳性表达率分别为13.3%、43.3%、61.4%和16.7%、40.0%、64.3%,Twist、HIF-1α在前列腺癌组织中的阳性表达率均高于前列腺增生组织和前列腺上皮内瘤变组织,差异有统计学意义（P〈0.01）;Twist、HIF-1α在相同前列腺病变组织间表达差异无统计学意义（P〉0.05）。②Twist及HIF-1α的表达均与前列腺癌的Gleason分级、临床分期及骨转移相关（P〈0.01,P〈0.05）,而与年龄无关（P〉0.05）。③Twist、HIF-1α在前列腺癌组织中过度表达,且两者之间呈显著正相关（r=0.63,P〈0.01）。结论 Twist、HIF-1α在前列腺癌发生演变过程中起着重要作用,同时检测两者的表达将有助于判断前列腺癌的预后。     

Continuous subgaleal suction drainage for the treatment of chronic subdural haematoma

Summary Background. Chronic subdural haematoma is one of the most common entities encountered in daily practice. Many methods of treatment have been reported, each with its own advantages and disadvantages. Method. The authors present a novel technique for the management of chronic subdural haematoma which is a variation of a closed drainage system. After evacuation of the haematoma through a single burr hole, we inserted a Jackson Pratt drain into the subgaleal space, with suction facing the burr hole, allowing for continuous drainage of the remaining haematoma. Findings. We used the method for over 4 years to treat 224 patients. Seventeen patients (7.6%) needed a second operation for a recurrence of the haematoma no patient required a third operation. Postoperative complications developed in 3 patients. Two patients died while in the hospital, a mortality rate of 0.9%. Conclusions. The use of suction assisted evacuation, is followed by results that compare satisfactorily to reports of previous methods, with a low rate of recurrence and complications. It is relatively less invasive and can be used in high risk patients.     

Is there a way to avoid surgical complications of twist drill craniostomy for evacuation of a chronic subdural hematoma?

Summary Background. Although twist drill craniostomy for evacuation of a chronic subdural hematoma is a rapid and minimally invasive procedure, it carries the risk of complications because it is a ‘blind’ technique. Our aim was to analyse the complications in a series of patients treated by this technique in order to identify methods of avoidance by modifications in the surgical technique. Method. Thirty-nine patients with a chronic subdural hematoma underwent twist drill craniostomy between November 2002 and December 2005 in our clinic. When a surgical complication happened we modified our surgical technique to see if this avoided it in future patients. Findings. Surgical complications happened in 7 patients (17.9%) including inadequate drainage, brain penetration, acute epidural hematoma and catheter folding. After preventive modifications these complications did not recur. Conclusions. Modifications in the technique of twist drill craniostomy are described in this paper which may minimise the occurrence of surgical complications.     

Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system

Uterine sarcomas are rare tumors that account for 3% to 7% of uterine cancers. Their histopathologic classification was revised by the World Health Organization (WHO) in 2003. The objectives of this study were to determine the frequency of different subtypes of uterine sarcoma applying the WHO criteria to a series of cases, compare the outcome of patients with different subtypes, and compare their immunoprofiles using a panel of immunomarkers. Thirty-four uterine sarcomas were identified for a 20-year period (1988-2008). Eighteen benign tumors of smooth muscle or endometrial stromal origin served as a comparison group. A tissue microarray was prepared and immunostaining performed for 10 selected oncoproteins involved in cell proliferation (Ki-67, P53, p16, and phosphatase and tensin homolog [PTEN]), cell differentiation (CD10, h-caldesmon, estrogen receptor, and progesterone receptor), and apoptosis (bcl-2 and Twist). Hierarchical clustering analysis of the immunohistochemical results was performed. The uterine sarcomas were classified as follows: 20 leiomyosarcomas, 9 endometrial stromal sarcomas, and 5 undifferentiated endometrial sarcomas. The outcome for patients with uterine sarcoma was poor, irrespective of histologic type, even for those with stage I tumors. Of the patients with follow-up available, 12 (67%) of 18 with leiomyosarcoma, 4 of 5 with undifferentiated sarcoma, and 4 of 7 with endometrial stromal sarcoma experienced recurrence and 8 patients with high-grade sarcomas died of tumor. In our series, most uterine sarcomas were leiomyosarcomas. Comparison was made between leiomyosarcomas that recurred and those with a favorable outcome and 3 patients with leiomyosarcoma without evidence of recurrence on long-term follow-up had tumors that were negative/low expressors of Ki-67, p53, p16, and Twist, with strong expression of bcl-2. A subset of undifferentiated endometrial sarcomas composed of cells with uniform nuclei may be a separate entity from those with nuclear anaplasia and may be related to low-grade endometrial stromal sarcomas. It may be possible to identify a subset of leiomyosarcomas with a favorable prognosis based on staining with a panel of immunomarkers for cell proliferation and apoptosis.