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Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer. .
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Humans , Lung Neoplasms , Carcinogenesis , InflammationABSTRACT
Lung cancer is the most common malignancy tumor. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer. Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase receptor in ERBB/HER family, which activates downstream signal transduction with other family members such as epidermal growth factor receptor (EGFR). HER2 gene mutation is closely related to the progression of many epithelial cell cancers. Tumors with high expression of HER2 show strong metastasis and invasion ability, poor sensitivity to chemotherapy, and are prone to relapse. At present, lung cancer driven gene targeted therapy has made rapid progress. Although the frequency of HER2 gene mutation in NSCLC is lower than that of EGFR, its driving mechanism in lung cancer is clear and partial targeted therapy is effective, which may become a new standard treatment in the future. This review focuses on the research progress of HER2 gene mutation in the treatment of NSCLC. .
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Objective To investigate the effect of signal transducers and activators of transcription 3(STAT-3)on sen-sitizing oral squamous cell carcinoma to cis-dichlorodiamineplatinum via downregulating miRNA-21. Methods Tscca and Tca8113P160 human tongue squamous cell carcinoma cell lines were employed in this study. WP1066 was used to suppress STAT-3 signaling pathway. Cells were divided into three groups:dimethyl sulphoxide (DMSO) group, cis-dichlorodiamine-platinum (DDP) group and WP1066+DDP group. Transcription level of miR-21 was assessed by real-time PCR, while the expression levels of STAT-3, p-STAT-3, tissue inhibitor of metalloproteinase-3 (TIMP-3) and matrix metalloproteinase-2/9 (MMP-2/9 ) were evaluated by Western blot assay. Matrigel matrix and transwell assay were used to determine cancer cell colony formation and invasive ability respectively. Expression level of miR-21 was examined by luciferase reporter gene as-say. Results Expression levels of STAT-3, pSTAT-3 and miR-21 were significantly suppressed by WP1066 treatment. The diameters of culture colony in cells treated with WP1066 and DDP were smaller than those in control group. The number of tongue cancer cells that migrated through the transwell membrane in WP1066 and DDP treated group was less than that in control group. Additionally, MMP-2/9 expression decreased while TIMP-3 increased dramatically in both cell lines in WP1066+DPP group compared to the other two groups. Conclusion Reduction of STAT-3 can sensitize oral squamous cell carcinoma to cis-dichlorodiamineplatinum via downregulating miR-21. Our study shows that DDP, in combination with WP1066, might be used as a potential target in the treatment of human oral squamous cell cancer.
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Long non-coding RNA (lncRNA) is a cluster with over 200 bp in length and has no protein-encoding product RNA, which is in-volved in cellular physiological or pathological process, especially in human oncogenesis. HOX transcript antisense RNA (HOTAIR), which is 2158 bp in length, is one of the most well-studied lncRNAs. Overexpression of HOTAIR is correlated with oncogenesis or me-tastasis in numerous epithelium original human cancers, including breast and colorectal cancers. Inhibiting HOTAIR expression could suppress cell growth and invasive ability of tumors. This review provides a brief summary of the latest progress in lncRNA-based can-cer research.
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Objective To investigate the influence of long non-coding RNA HOTAIR in proliferation and apoptosis of human tongue squamous cell carcinoma in vitro and in vivo. Methods siHOTAIR was used to inhibit the HOTAIR expression in Tb3.1 human tongue squamous cell carcinoma cell line. The experiments were divided into siHOTAIR group, nonsense sequence group and blank control group. Real-time PCR was used to detect the HOTAIR expression. MTT assay was employed to determine the cell survival. The expression levels of Bcl2, BAX, caspase-3, cleaved caspase-3 were examined by Western blot assay. Tb3.1 xenograft tumor model was established in BALB/c nude mice, and the tumor model was divided into control group, negative group, and siHOTAIR treated group. The tumor tissues were measured by immunohistochemistry stain (IHC) and TUNEL assay. Results The detection of real-time PCR showed that HOTAIR expression was reduced after treated with siHOTAIR. Western blots assay showed that Bcl-2 protein was suppressed while cleaved caspase-3 and BAX protein were up-regulated after treated with siHOTAIR. MTT assay indicated that the cell survival rate was significantly reduced in siHOTAIR treated group. Flow cytometry detected that apoptosis levels were increased in siHOTAIR group. The level of cell senescence was higher in the siHOTAIR group than that of control group. Results of IHC indicated that Ki-67 and Bcl-2 protein of tumor tissue were inhibited, while BAX and cleaved caspase-3protein expressions were elevated simultaneously in the siHOTAIR group. TUNEL assay suggested that more apoptosis was observed in siHOTAIR group. Conclusion HOTAIR can affect proliferation and apoptosis of tongue squamous cancer cells. HOTAIR may be one of the new candidate targets for human tongue cancer therapy.
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Objective:To investigate the risk factors of central lymph node metastasis (CLNM) and lateral neck lymph node me-tastasis in papillary thyroid microcarcinoma (PTMC) patients, and to analyze the importance of high resolution ultrasonography in the diagnosis of lateral neck lymph node metastasis in PTMC patients. Methods:A retrospective protocol was applied, and a total of 1 037 PTMC patients were reviewed. These patients underwent central lymph node dissection or thyroidectomy with lateral neck lymph node dissection between January and November in 2013 in the Tianjin Medical University Cancer Institute and Hospital. Clinicopathological factors, namely, age, sex, primary tumor size, multifocality, bilateralism, thyroid capsular invasion, and local invasion, were analyzed. Results: CLNMs were found in 332 of 1037 patients (32.0%), and 71 out of 1037 patients had lateral neck lymph node metastasis (6.85%). In the univariate analysis, patients with the following risk factors were at high risk of CLNM (P5 mm, multifocality, bilateralism, thyroid capsular invasion, and local invasion. Male patients with cen-tral lymph node metastasis positively showed high lateral neck lymph node metastasis rate (P5 mm, multifocality, bilateralism, thyroid capsular invasion, and lo-cal invasion). The importance of high-resolution ultrasonography in diagnosing lateral neck lymph node metastasis was revealed by the results. Thus, this method should be widely popularized. Radical neck dissection should be performed in male patients who received a positive diagnosis via ultrasonography or those with PTMC who had more than three positive nodes in the central lymph node metasta-sis. However, given the high occurrence rate of PTMC, a prospective study needs to be conducted in the future.
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Objective To explore the expressions of Cyclin-dependent kinase 5 (CDK5) and Epithelial-Mesenchymal Transition (EMT) related proteins including N-cadherin, Vimentin and E-cadherin in head and neck squamous cell carcino? ma (HNSCC), and to determine the relationship between the expression of CDK5 and prognosis. Methods The expression levels of CDK5 and EMT related proteins were evaluated by immunohistochemistry in 55 patients who were diagnosed as HN?SCC. They were also analyzed in different clinical pathological factors. The correlation of CDK5 and EMT related proteins as well as the relationship between the expression of CDK5 and prognosis were also analyzed. Results The expression level of CDK5 was significantly higher in patients with lymph node metastasis than that in patients with non-lymph node metastasis (91.67%vs 30.23%, P<0.05). It’s also higher in T3-T4 stages than that in T1-T2 stages (85%vs 20%, P<0.05). The ex?pression levels of N-cadherin and Vimentin were significantly higher in patients with lymph node metastasis than those in patients with non-lymph node metastasis (75.00%vs 6.98%;91.67%vs 27.91%, all P<0.05). However, the expression level of E-cadherin was significantly lower in patients with lymph node metastasis (8.33%vs 86.05%, P<0.05) compared to that in patients without. CDK5 was positively correlated with N-cadherin and Vimentin, but negatively correlated with E-cad?herin (rs=0.512, 0.443,-0.363, all P<0.01). The 3-year survival rates were significantly lower in patients with high expres?sion of CDK5 (37.5%) than that in patients with low expression of CDK5 (87%, Log-rankχ2=12.678, P<0.01). Conclusion CDK5 and EMT related proteins were activated abnormally in HNSCC with lymph node metastasis. CDK5 may be a new bio?logical marker for prognosis of HNSCC.
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BACKGROUND: Telomerase can maintain the telomere length and avoid cel replicative senescence and apoptosis in somatic cells. Its catalytic subunit cal ed telomerase reverse transcriptase has roles in mediating cellsurvival and anti-apoptotic functions. OBJECTIVE: To evaluate the effects of human telomerase reverse transcriptase on amyloid β1-40-induced human embryonic cortical neurons injury. METHODS: Human cortical neurons derived from 12-16 weeks old aborted fetuses were transfected with recombinant adenovirus vector encoding human telomerase reverse transcriptase. Expression of human telomerase reverse transcriptase was evaluated by immunocytochemical staining. Telomerase activity was measured using a PCR-based telomeric repeat amplification protocol enzyme-linked immunosorbent assay kit. Human embryonic cortical neurons were treated with 10 μmol/L ol/L amyloid β1-40 after transfected for 3 days. Cel viability, reactive oxygen species levels and glutathione contents in human embryonic cortical neurons were respectively detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate and chromatometry. RESULTS AND CONCLUSION: Expression of human telomerase reverse transcriptase reached peak at 3 days after transfection, and the telomerase activity was rebuilt; 10 μmol/L amyloid β1-40 could significantly reduce the cel viability of neurons and glutathione content (P < 0.05 and P < 0.01), and increase the reactive oxygen species levels (P < 0.05). The neurons transfected with human telomerase reverse transcriptase gene could be significantly against the toxicity of amyloid β1-40 and increase the cel viability and glutathione content (P < 0.05 and P < 0.01), and decrease the reactive oxygen species levels (P < 0.05). The results indicate that human telomerase reverse transcriptase can protect amyloid β1-40-induced human embryonic cortical neurons injury