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991.

Background

TONSL has been suggested to function as an oncogene in lung, esophageal and cervical cancer. This study was aimed to identify the expression of TONSL and its role in hepatocellular carcinoma (HCC).

Methods

By data mining in the Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases, the expression profile of TONSL, its clinical significance, the potential mechanisms of its dysregulation and its underlying biological function in HCC were investigated.

Results

TONSL was significantly upregulated in HCC tissues relative to normal liver tissues (P?<?0.05). High TONSL expression was significantly correlated with advanced TNM stage, poorly differentiated tumors, vascular invasion, elevated serum alpha-fetoprotein expression and a worse prognosis (all P?<?0.05). Multivariate analysis further confirmed that TONSL overexpression was an independent risk factor for poor overall survival (OS) and recurrence-free survival (RFS) in HCC (all P?<?0.05). Additionally, 16% of HCC cases (n?=?370) had TONSL DNA amplification. The total methylation level of TONSL was moderately and negatively correlated with its mRNA expression (P?<?0.05). TONSL was predictively targeted by miR-133b, which was downregulated in HCC and negatively related to TONSL mRNA expression (all P?<?0.05). Kaplan-Meier analyses demonstrated that low miR-133b expression was significantly associated with poor OS and RFS (all P?<?0.05). Moreover, gene set enrichment analysis revealed that cases with TONSL overexpression were enriched in cell cycle regulation pathways (all P?<?0.05).

Conclusions

TONSL holds promise for serving as a prognostic biomarker for HCC. DNA amplification, hypomethylation and miR-133b downregulation could be the mechanisms associated with TONSL upregulation in HCC. TONSL might function as an oncogene via cell cycle regulation pathways in HCC.  相似文献   
992.
《Immunobiology》2022,227(6):152298
PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.  相似文献   
993.
低氧促进P19细胞向多巴胺能神经元分化   总被引:1,自引:0,他引:1  
目的观察低氧对P19细胞神经分化的影响,针对其向多巴胺能神经元分化的现象及机制进行探讨。方法实验分为常氧组(20%O2)和低氧组(3%O2,每天低氧10 m in)。对诱导分化的神经元采用免疫细胞化学染色方法鉴定。用流式细胞术及W estern b lot检测多巴胺能神经元,高效液相色谱法测定分泌的多巴胺。用RT-PCR技术检测低氧诱导因子HIF-1αmRNA水平。结果①在分化的P19细胞中,低氧组神经元含量高于常氧组(P<0.05),低氧组多巴胺能神经元含量及所分泌的多巴胺显著高于常氧组(P<0.001);②低氧组诱导期HIF-1αmRNA表达水平明显高于常氧组。结论低氧可以促进P19细胞的神经分化,尤其促进P19细胞向多巴胺能神经元分化,HIF-1α可能在其中起了一定作用。  相似文献   
994.
目的构建7q32区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞的部分基因表达图谱。方法通过差异RT-PCR和Northern杂交的方法检测定位于7q32区域的20个EST在鼻咽癌细胞和鼻咽癌组织及原代培养人正常鼻咽上皮细胞mRNA的表达水平。结果8个EST在鼻咽癌细胞HNE1和原代培养人正常鼻咽上皮细胞中表达量较一致,7个EST在两种细胞中均无表达,3个EST(W72688、H19830、AA130630)在鼻咽癌细胞株中表达上调,而2个EST(AA070437、H90882)在原代培养人鼻咽上皮细胞中表达上调。在13例鼻咽癌活检组织中30.7%(4/13)的AA070437表达下调,77%(10/13)的W72688和77%(10/13)的H19830表达上升。结论构建了7q32区域鼻咽癌细胞和组织及原代培养人正常鼻咽上皮细胞部分基因表达图谱,并初步认为A070437的表达下调和W72688、H19830的过表达与鼻咽癌的发生有关。  相似文献   
995.
Geographic or ethnic differences in the incidence of thyroid carcinoma, as well as in the histologic distribution of thyroid carcinoma between Japan and Western countries, have been described but are still unclear. The recent establishment of histologic criteria for the diagnosis of thyroid carcinoma by the WHO committee has facilitated the comparison of clinicopathological data of patients with thyroid carcinoma all over the world. The aim of the present review article is to clarify the epidemiological and clinicopathological differences of thyroid carcinoma between Japan and Western countries. We found recently no significant differences in the incidence, mortality, and histologic distribution of thyroid carcinoma between Japan and Western countries; this was contrary to our expectation. This is likely attributable to westernization of the Japanese diet, standardized medical levels, and international standardization of histologic criteria of thyroid carcinoma.  相似文献   
996.
997.
目的:对接受调强放射治疗的鼻咽癌病人进行治疗前的剂量验证.材料和方法:利用电离室,胶片和验证模体对39个接受调强放射治疗的鼻咽癌患者,在治疗开始前进行绝对剂量和相对剂量验证.绝对剂量验证主要在两个位置进行:一个在等中心位置,另一个在离等中心4cm靠进腮腺的位置.相对剂量主要用体模对单野和整个计划的剂量分布进行验证.将得到的剂量分布利用分析软件与计划中的剂量分布进行分析比较.利用剂量偏差(dose difference)、吻合距离(distance to agreement,DTA)、γ指数等参数来测量剂量验证的偏差.结果:中心点和腮腺边上点的平均绝对误差分别为2.70%和3.03%.对于测量感兴趣区域(ROI,region of interested)的相对误差的测量,90%的测量都在设定的标准(3%,3 mm)之内,对于未能达到剂量偏差和间距偏差标准的区域,结合γ分析后一般也可以得到满意的结果.结论:验证结果表明实际测量剂量分布与计划计算的剂量分布符合的相当理想.  相似文献   
998.
AIMS: To study cyclooxygenase-2 (COX-2) expression in ductal carcinoma in situ (DCIS) of the breast and its association with histological features. COX-2, an inducible prostaglandin synthase, has been shown to be important in mammary carcinogenesis, being associated with increased tumour size and unfavourable outcome in breast cancer. Animal studies indicate that COX-2 inhibition is effective in the prevention and treatment of mammary cancers. METHODS AND RESULTS: Fifty-one cases of DCIS diagnosed during 1990-2000 were reviewed. Immunohistochemistry for COX-2 was performed and the COX-2 staining scores were correlated with histological features. The majority of cases [41 of 51 (80%)] had positive COX-2 staining, of which 13 cases (25%) had strong staining. High nuclear grade DCIS was significantly associated with increased COX-2 staining (P = 0.04). CONCLUSIONS: High-grade lesions are known to be associated with a higher recurrence rate following excision and are often oestrogen receptor negative, and as such, may be less responsive to adjuvant tamoxifen therapy. There is a need to examine further the role of COX-2 expression in DCIS, as both a prognostic and predictive factor.  相似文献   
999.
目的:构建受AFP顺式作用元件调控的超抗原表达载体,将SEA(D227A)特异性的表达于AFP阳性肝癌细胞膜表面。方法:PCR扩增AFP基因启动子、增强子、linker—CD80tm和SEA(D227A)。将上述片断插入逆转录病毒载体pLXSN的多克隆位点,构建AFP基因顺式作用元件调控的肝癌特异性减毒超抗原表达载体(pLXSN SEA(D227A)—linker—CD80tm)。通过脂质体介导,以表达载体转染表达或不表达AFP的肿瘤细胞系,用RT—PCR和间接免疫荧光染色,检测SEA的表达。结果:成功地将AFP基因的启动子、增强子、linker—CD80tm和SEA(D227A)克隆到逆转录病毒载体pLXSN的多克隆位点,酶切鉴定和DNA序列分析无误,RT—PCR和间接免疫荧光法检测证实,SEA(D227A)能在AFP阳性的肝癌细胞膜特异性表达。结论:AFP顺式作用元件修饰的超抗原表达载体的构建,为下一步用其强化肝癌的免疫治疗奠定了基础。  相似文献   
1000.
AIMS: The objectives of this study were: (1) to determine, using immunohistochemistry, the level of expression of the cell cycle factors p53, p21 and cyclin D1 in a group of bronchioloalveolar carcinomas (BACs), and to compare these data to relevant published data for lung carcinoma; (2) to determine if higher expression rates for these factors in BAC were associated statistically with advanced clinical stage, greater tumour size, tobacco abuse, and/or BAC subtype; (3) to seek, using Fisher's exact t-test and paired data groups, any significant associations within the expression data for p53, p21 and cyclin D1. METHODS AND RESULTS: A panel of monoclonal antibodies against p53, p21 and cyclin D1 was applied to 19 bronchioloalveolar carcinomas (17 surgical pathology cases and two autopsies) from the tissue archives of St. Louis University. These immunohistochemical stains were graded on a semiquantitative scale according to the prevalence of nuclear staining within the tumour (< 10% positive cells = 0, 10-25% = 1+, 25-50% = 2+, 50-75% = 3+ and 75-100% = 4+). Six of 19 (32%) of BACs showed 1+ or greater p53 positivity, six of 19 (32%) showed 1+ or greater nuclear cyclin D1 positivity, and nine of 19 (47%) of BACs showed 1+ or greater p21 nuclear positivity. A statistically significant correlation was found between p53 and cyclin D1 expression (P = 0.046, Fisher's exact t-test), but not between p53 and p21, or between p21 and cyclin D1. No statistically significant association was found between the cell cycle factor expression data and subtype of BAC (mucinous vs. nonmucinous), tumour diameter, clinical stage or tobacco-use history. CONCLUSIONS: BACs show p53 immunostain positivity at a frequency similar to that published for p53 mutations in lung adenocarcinomas in general. Cyclin D1 and p21 nuclear expression characterizes a significant proportion of BACs, with cyclin D1 and p53 expression showing a statistically significant association. Aberrations in p53, p21, and cyclin D1 expression may be important in the development of a significant proportion of BACs.  相似文献   
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