Abstract: Objective To investigate the expression of inhibitor of apoptosis gene Livin and its relationship with expression of P53,Bcl-2 in esophageal carcinoma tissues. Methods The expression of Livin messenger ribonucleic acid (mRNA) in 36 esophageal carcinoma tissues and 18 paracancerous tissues were measured by reverse transcriptionpolymerase chain reaction (RT-PCR) combined with silver staining technique. The expression of Livin, P53 and Bcl-2 proteins were detected by immunohistochemical method (streptavidin-peroxidase). Results RT-PCR results: Livin mRNA positive expression of esophageal carcinoma tissues was more evident than that of paracancerous tissues, the expression of both variants was simultaneous basically. Immunohistochemical results: the Livin protein positive expression rate of esophageal carcinoma tissues was higher evidently than that of paracancerous tissues(Plt;0.01). Livin protein positive expression rate of external coat of esophagus invaded by carcinoma was higher than that of tunica muscularis esophagi invaded by carcinoma(Plt;0.05); Livin protein positive expression rate of lymph node metastasis was higher than that of normal lymph node (Plt;0.05). The expression of Livin protein was not related to the expression of P53 protein（χ2=1.00,P=0.505）,but it was positively related to the expression of Bcl-2 protein（χ2=10.60，P=0.003）. Conclusion Aberrant expression of Livin may be a new target for diagnosis and gene treatment of esophageal carcinoma.The aberrant expression of Livinand apoptosis related gene Bcl-2 may play synergetic roles in process of carcinogenesis of esophageal carcinoma.
Objective To observe the effect of gene expression of p53 and the polymorphism of p53 gene codon 72 on cl inical phenotype of keloids. Methods The tissue and blood samples were taken from 35 patients with keloids, 19 males and 16 females, and the course of disease was from 4 months to 8 years. Meanwhile, autologous peripheral blood was collected for genotype analysis. According to the observing scope, the tissue samples of the keloids were divided into 2 groups: the central group involving the central part of the keloids (the central area within two-thirds of the radius) and the peripheral group involving the peripheral part of the keloids (the peripheral area within one-third of the radius). According to the largest diameter of the keloids, the two groups were divided into 3 subgroups: the small size group with 5 patients (lt; 1 cm), the medium size group with 21 patients (1-3 cm) and the large size group with 9 patients (gt; 3 cm). DNA of the tissue and blood samples were extracted, and the PCR followed by DNA sequencing was used to detect the polymorphism of p53 gene codon 72. The expression change of P53 was detected by immunohistochemical staining. The fibroblast apoptosis in keloid tissues was detected by TUNEL method. Results The genetic genotype of p53 gene codon 72 in keloids included Arg/Arg in 7 cases, Pro/Arg in 21 cases, Pro/ Pro in 7 cases. The significant correlation was found between genotype and cl inical phenotype (P lt; 0.05). Immunohistochemical staining revealed that P53 was detectable in peripheral and central groups of small-medium size keloids and central groups keloids, and detectable in few cells in peripheral groups of large size keloids. The absorbency value was 3 439.359 8 ± 538.527 5 in Arg/Arg genotype, 3 273.186 2 ± 375.213 9 in Arg/Pro genotype, 1 691.372 9 ± 98.989 3 in Pro/Pro genotype. There weresignificant differences among the three genotypes (P lt; 0.05). The fibroblast apoptosis was detected by TUNEL, and the apoptotic cells were evenly distributed. The apoptosis index was 31.000 0 ± 3.266 0 in peripheral group of large size keloids, 42.300 0 ± 4.354 8 in peripheral group of medium size keloids, 44.600 0 ± 5.253 6 in peripheral group of small size keloids. There were significant differences among the three groups (P lt; 0.05). Conclusion There is close relationshi p between the cl inical phenotype of keloids and the expression of P53. The polymorphism variation of p53 gene codon 2 is beneficial for apoptosis of fibroblasts in keloids.
Objective To explore the expression of CD105 protein in esophageal squamous cell carcinoma and it＇s relationship with P53 protein. Methods Using streptavidin biotinperoxidase （SP） method, the expression of CD105 protein and P53 protein in esophageal squamous cell carcinoma were examined in normal esophageal tissues （n=10） and esophageal squamous cell carcinoma tissues（n=86）. Results The expression positive rate of CD105 protein was 74. 4%（64/86） in esophageal squamous cell carcinoma , 0% in normal esophageal epithelium. Expression positive rate of CD105 protein was 66. 1%（37/56） in early stage （stage Ⅰ-Ⅱ ）, 90.0% （27/30） in later stages （stage Ⅲ-Ⅳ ）. The expression of CD105 protein were bly associated with P53 protein（P〈0. 05）. Conclusion CD105 protein may participate in the onset and progression of esophageal squamous cell carcinoma. CD105 protein could he a new diagnostic /therapeutic target in esophageal squamous cell carcinoma.
Objective To evaluated the role of wt-P53 protein in telomerase regulation in keloid fibroblasts(KFBs). Methods The fibroblasts were derived from humankeloid tissue which was proved by pathological diagnosis. KFBs were divided into 2 groups, the transfection group and the untransfection group. wt-p53 gene was transfected into the fibroblasts by adenovirus vectors in the transfection group. The KFBs untransfected with wt-p53 gene served as control (untransfection group). After 48 hours of transfection, the expression of wt-P53 protein was analyzed by both Western blotting and immunofluorescence method, respectively. The telomerase activity was evaluated by TRAP-ELISA after 1-7 days of transfection. Results All the KFBs from 2 groups expressed wt-P53 protein. But the expression level of wt-P53 protein in the transfection group was significantly higher than that in the untransfection group.At the same time of high expression of wt-P53 protein, the telomeraseactivity of KFBs in transfection group was significantly lower than that in theuntransfection group(P＜0.05). Conclusion High level expression of wt-P53 protein can transiently inhibit the telomerase activity of KFBs.
ObjectiveTo systematically review the correlation between the expression of P53 and nasopharyngeal carcinoma. MethodsDatabases including The Cochrane Library (Issue 1, 2016), PubMed, EMbase, CBM, CNKI, VIP, and WanFang Data were searched from the inception to January 1st 2016 to collect case-control studies about the correlation between the expression of P53 and nasopharyngeal carcinoma, as well as its clinically pathologic features. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.2 software. Results Twelve studies were finally included in this meta-analysis. There were 630 cases of nasopharyngeal carcinoma and 253 controls. The results of meta-analysis showed that, the expression of P53 protein were significantly different between the nasopharyngeal carcinoma group and the control group (OR=21.34, 95%CI 13.59 to 33.50, P < 0.000 01), between the nasopharyngeal carcinoma with lymphatic node metastasis group and without lymphatic node metastasis group (OR=3.69, 95%CI 1.67 to 8.17, P=0.001), between the clinical stage Ⅰ to Ⅱ group and the clinical stage Ⅲ to Ⅳ group (OR=0.19, 95%CI 0.08 to 0.49, P=0.000 6). However, there were no significant differences in expression of P53 between the male nasopharyngeal carcinoma group and the female nasopharyngeal carcinoma group (OR=0.92, 95%CI 0.49 to 1.74, P=0.80), and between the < 50 nasopharyngeal carcinoma group and the≥50 nasopharyngeal carcinoma group (OR=1.70, 95%CI 0.70 to 4.11, P=0.24). ConclusionsCurrent evidence shows that, the expression of P53 protein is associated with the occurrence, development of nasopharyngeal carcinoma and may be positively correlated to degree of tumor malignance. It may be an indicator poor prognosis.
Objective To observe the expressions of P53 and CD34 in rectal cancer and distal mucosa and to explore the safe distal margin of radical surgery for rectal cancer at molecular pathologic level. Methods Forty-five cases of rectal cancer were marked before operation， and then the cases were detected by PET/CT. P53 and CD34 expressions in rectal tissues were detected by immunohistochemistry technique. Results P53 expression and microvessel density (MVD) in rectal cancer were significantly higher than those in distal mucosa， which in distal mucosa were decreased along the anal direction. P53 and CD34 were still found in the normal rectal tissue. P53 expression and MVD were not significantly different between in more than 1.5 cm distal rectal mucosa and in normal rectal tissue. Besides MVD was related to size of tumor in rectal cancer and distal 0.5 cm rectal mucosa tissue, P53 and CD34 in rectal cancer and distal mucosa rectal tissue were not associated with tumor diameter, stage and differentiation of rectal cancer. Conclusion From the molecular pathologic view, the resection of 2.0 cm rectal distal tissue should be safe for excision of rectal cancer.
Precision medicine is a new strategy that aims at preventing and treating human diseases by focusing on individual variations in people's genes, environment and lifestyle. Precision medicine has been used for cancer diagnosis and treatment and shows evident clinical efficacy. Rapid developments in molecular biology, genetics and sequencing technologies, as well as computational technology, has enabled the establishment of "big data", such as the Human Genome Project, which provides a basis for precision medicine. Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high incidence rate and low survival rate. Current therapies are often aggressive and carry considerable side effects. Much research now indicates that precision medicine can be used for HNSCC and may achieve improved results. From this perspective, we present an overview of the current status, potential strategies, and challenges of precision medicine in HNSCC. We focus on targeted therapy based on cell the surface signaling receptors epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor-2 (HER2), and on the PI3K/AKT/mTOR, JAK/STAT3 and RAS/RAF/MEK/ERK cellular signaling pathways. Gene therapy for the treatment of HNSCC is also discussed.
目的:分析基底細胞癌中P53蛋白的表達情況,探討P53蛋白的表達與基底細胞癌發生發展的關系,以及在基底細胞癌發病機制中的作用。方法:選取2006年7月至2007年2月,北京朝陽醫院皮膚科手術切除的基底細胞癌及正常皮膚組織石蠟標本各17例,免疫組織化學法分析P53蛋白在基底細胞癌和正常皮膚組織中的表達情況。結果:17例基底細胞癌中P53蛋白的表達率為100%。綜合染色強度和陽性細胞所占比例進行平均半定量分析,P53蛋白在基底細胞癌中表達程度為,而在正常皮膚組織中表達程度為+,兩者之間存在統計學上顯著性差異。結論:P53在基底細胞癌中呈現高度表達狀態,提示P53蛋白的表達與基底細胞癌的發病過程關系密切,可能在其發生發展過程中起重要作用。
A series of novel polycyclic spiro-fused carbocyclicoxindoles were synthesized and investigated for their in vitro antiproliferative activities against nine human cancer cell lines. Five compounds (10i, 101, 10n, 10p, and 10r) demonstrated anticancer activities against A2780s cells with IC50 values of less than 30 mu M. In particular, compound 10i showed anticancer activities against seven cancer cell lines and stronger activities than cisplatin in A2780s, A2780T, L126, and HCT116 cells. Further studies illustrated that compound 101 arrested cell cycle in G1 phase and induced apoptosis of HCT116 cells. This compound also effectively increased the protein levels of cleaved caspase-3, p53, and MDM2. Molecular docking results revealed that compound 101 could bind well to the p53-binding site on MDM2, indicating that it might work by blocking the MDM2-p53 interactions. (C) 2016 Elsevier Masson SAS. All rights reserved.