MicroRNAs and liver cancer: Recent progress / 第二军医大学学报

MicroRNA (miRNA) is a small non-coding RNA that contains 21 to 23 nucleotides and can down-regulate gene expression by translational repression. Recent studies found that some miRNAs might function both as oncogenes and tumor suppressors; its role in the tumorigenesis may complement and enrich the mechanisms of tumorigenesis. Liver cancer is a great threat to human health, whose pathogenesis is still not completely understood. MiRNAs can influence the tumorigenesis, differentiation and treatment of liver cancer. Here we summarizes the related progression in research of miRNA and liver cancer.

Aspectos moleculares da tumorigênese hipofisária: [revisão] / Molecular aspects of pituitary tumorigenesis: [review]

Os tumores hipofisários, adenomas em sua quase totalidade, são de ocorrência freqüente, representando 10 por cento a 15 por cento de todas as neoplasias intracranianas. Estas lesões são classificadas em microadenomas (< 10 mm) ou macroadenomas (> 10 mm) e como secretoras ou quiescentes (não-funcionantes). Estes tumores são capazes de secretar, de maneira autônoma, os hormônios adenohipofisários, como o hormônio de crescimento (GH), a prolactina (PRL), o hormônio adrenocorticotrófico (ACTH), o hormônio tireotrófico (TSH), o hormônio folículo estimulante (FSH) e o hormônio luteinizante (LH). A ocorrência de metástase, caracterizando um carcinoma hipofisário, é bastante rara, mas são relativamente comuns tumores de comportamento agressivo que exibem sinais de invasão local. Embora a sua patogênese ainda não seja plenamente caracterizada, muitos mecanismos moleculares envolvidos na tumorigênese hipofisária já foram desvendados. Nesta revisão, serão descritos avanços consideráveis realizados na última década relativos à compreensão dos fatores envolvidos na progressão tumoral, incluindo a participação de oncogenes, supressores tumorais e fatores de crescimento.

Pituitary tumors, almost invariably adenomas, are of frequent occurrence, accounting for 10 percent to 15 percent of all the intracranial neoplasm. They are classified as microadenomas (< 10 mm) or macroadenomas (> 10 mm) and as secreting or clinically non-secreting (or not functioning) adenomas. These tumors are autonomously capable to release pituitary hormones such as the growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The occurrence of metastases, characterizing a pituitary carcinoma, is exceedingly rare. However tumors with aggressive behavior, leading to local invasion, are relatively common. Although the pathogenesis of pituitary tumors is fully characterized, many molecular mechanisms of pituitary tumorigenesis had already been revealed. This review intents to describe advances in the understanding of the involved advances that have been made in the last decade concerning pituitary tumors progression, including the participation of oncogenes, tumor suppressor genes and growth factors.

Detection of Apoptosis by M30 Monoclonal Antibody in Non-small Cell Lung Carcinomas / 대한흉부외과학회지

BACKGROUND: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. MATERIAL AND METHOD: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were performed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. RESULT: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; 61.7+/-26.8 cells vs. p53 negative group; 45.6+/-29.6 cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, AI > or =1) on M30 staining (p53 positive group; 52.4% [11/21] vs. p53 negative group 16.7% [4/24], p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and AI showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% CI 1.886~29.678; p=0.004) and the risk of recurrence almost 3.8-fold (R.R 3.795; 95% CI; 1.184~12.158; p=0.025) in the high AI (> or =1) compared to the low AI (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. CONCLUSION: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

p73 gene protein expression in lung cancer as related to clinicopathological characteristics and prognosis in the elderly / 中华老年医学杂志

Objective To study the expression of p73 gene in lung cancer and tumorigenesis, progression of lung cancer in the elderly. Methods The expression of p73 protein in 65 cases of lung cancer, adjacent tissues of cancer and normal tissues was determined by immunohistochemical SABC method. The results were analysed by combining the clinicopathological data and the prognosis. Results The results showed (1)the expression level of p73 protein in the cancer group was significantly different from the rest groups(47 7%,9 2%,4 6%, P 0 05),but it was correlated with the clinical stage (60 5%,22 7%) and survival time of the patients (72 2%,16 0%, P

Expression and significance of smad_4mRNA,TGF-?_1 ,and TGF-?R_1 in pancreatic carcinoma / 中国普通外科杂志

Objective To study the significance of expressions of smad_4mRNA,TGF-?_1, and TGF-?R_1 in pancreatic carcinoma(PC) . Methods Smad_4mRNA was detected by in situ hybridization. TGF-?_1 and TGF-?R_1 were detected by immunohistochemical method. Results The positive rates of smad_4mRNA,TGF-?_1 and TGF-?R_1 were singnificantly lower in 53 slices of pancreatic carcinoma than those in 25 slices of paracancerous tissue (all P

Serum melanoma-inhibiting activity protein in uveal melanoma / 中华眼底病杂志

Objective To detect the level of serum melanoma-inbibiting activity (MIA) in patients with uveal melanomas, and investigate the value of MIA in diagnosing and inspecting uveal melanomas. Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of MIA in peripheral serum of 27 patients with uveal melanoma, 6 with melanocyte tumor, 7 with other ocular tumors and 16 healthy individuals, respectively. Results The concentration of MIA in patients with uveal melanoma was significantly higher than that in the healthy ones (16 individuals) and the patients with adenoma of non pigmented ciliary epithelium (4 patients), retinoblastoma (2 patients), and retinal angioma 91 patient). The concnetration of MIA in patients with uveal melanoma without scleral infiltration or remote metastasis was obviously lower than that in the patients with scleral infiltration or remote metastasis, but didn′t differ much from which in the patients with melanocyte tumor. In the patients with uveal melanoma without infiltration or remote metastasis, there was no significant difference of MIA level between patients with spindle cell and mixed and epithelioid cell. Conclusion The level of serum MIA may be an effective index in diagnosing uveal melanoma, which can monitor the metastasis of uveal melanoma.

SUPPRESSION EFFECT OF ADENOVIRUS-MEDIATED GENE TRANSFER OF PTEN AND TIMP-2 ON INVASION OF HUMAN U87 GLIOMA CELLS IN VITRO / 解放军医学杂志

Objective To evaluate the effects of adenovirus mediated gene transfer of TIMP 2 and PTEN on invasion of human U87 glioma cells in vitro . Methods U87 cells were transinfected with AdTIMP 2 and AdPTEN in vitro . The mRNA and protein expressions of TIMP 2 and PTEN were detected with RT PCR and Western blotting, respectively. The relative activity of MMP 2 and MMP 9 was determined by gelatin zymogram, and invasion of U87 in vitro was observed using Boyden chamber. Results Gene and protein expressions of PTEN and TIMP 2 were shown to be up regulated when U87 was transinfected with AdPTEN and AdTIMP 2. The number of invasion cells of U87 infected with AdX gal, AdPTEN, AdTIMP 2 and PTEN+TIMP 2 was 55 64 13 27, 48 26 14 75, 35 27 10 94, 27 38 12 81, and 19 16 5 45, respectively. In vitro invasion of glioma cells was significantly inhibited after infected with AdTIMP 2 and/or AdPTEN, while the inhibition effect was more remarkable in the combined group than that in single group, and it was not consistent with the change in MMPs activity. Conclusion These results imply that combined TIMP 2 and PTEN gene therapy mediated by adenorirus may be useful for anti invasion therapy of malignant glioma

Effects of simvastatin on PDGF-BB and serum-induced proliferation of vascular smooth muscle cells and on the expression of tumor suppressor gene PTEN / 中国病理生理杂志

AIM: To observe the effect of simvastatin on the proliferation of vascular smooth muscle cells(VSMCs) induced by serum and growth factor PDGF-BB and the effect of simvastatin on the expression of PTEN,a important regulator of G 1/S cell cycle transition. METHODS: The DNA synthesis was determined by -TdR incorporation, cell cycle was examined with flow cytometry, the protein level of PTEN was measured by Western blot method. RESULTS: (1)Simvastatin inhibited -TdR incorporation in a dose dependent manner. (2) Flow cytometric DNA analysis revealed that simvastatin induced significantly enhancement of G 0/G 1 phase and decrease in S phase VSMCs.(3)Simvastatin increased protein level of PTEN and mevalonate, a metabolite of HMG-COA, reversed the effect of simvastatin on PTEN protein expression. CONCLUSION: Simvastatin may inhibit proliferation of VSMCs and retarded cell cycle in G 0/G 1 phase by increasing PTEN expression through inhibiting synthesis of mevalonate.

Expression of nm23 gene and its significance in heterotransplanted model of retinoblastoma in nude mice / 中华眼底病杂志

Purpose To investigate nucleoside diphosphate kinase (NDPK ) expression of tumor metastasis suppressor gene nm23 in heterotransplanted model of retinoblastoma(RB) in nude mice,and analyse the correlation between the expression of nm23 gene and the formation and progression of heterotransplanted RB. Methods SP immunohistochemical method was used to detect the expression of nm23 gene product NDPK in 20 tumors of heterotransplanted RB model and normal retinal tissue. Results The negative staining of nm23/ NDPK was found in normal retinal tissue , whereas 100% expression rate in RB tumors with positive number of 48.73?2.37. No statistical significance of the expression of nm23/ NDPK was observed between the intraocular growth phase (I～Ⅲ grade) and invasive phase (Ⅳ～Ⅴ grade) in heterotransplantedRB tumors. Conclusion The function of nm23 gene as a tumor metastasis suppressor in heterotransplanted RB tumors was less prominent ,but it may play a role in carcinogenesis and progrssion of RB and may predict poor prognosis.

Relationship between absence of expression of DPC4/SMAD4 gene and pathogenesis of pancreatic carcinoma / 中国普通外科杂志

Objective To review the relationship between absence of expression of DPC4/SMAD4 gene and pathogenesis of pancreatic carcinoma(PC). Methods A summerized paper was made on the review of relative literatures. Results and Conclusions A new gene DPC4 (located on chromosome 18q21.1 region) has been identified as a candidate tumor suppression gene. SMAD4 belongs to the evolutionarily conserved family of SMADs proteins that are crucial intracellular mediators of signals from the transforming growth factor ?(TGF-?). In TGF-? super family signal pathways, SMAD4 plays a pivotal role .There is a close relationship between absence of expression of DPC4 gene and pathogenesis of pancreatic carcinoma.

Gene transfer of human ANGPTL4 mediated by recombinant retroviral vector inhibits the growth of liver cancer / 中国普通外科杂志

Objective To construct recombinant retroviral vector containing human hepatocellular carcinoma-related gene ANGPTL4 ( angiopoietin-like 4) cDNA and to evaluate antitumor effect of recombinant retroviral vector-mediated human ANGPTL4 gene transfer. Methods ANGPTL4 cDNA was cloned in vitro from human liver cell lines HL-7702 and subcloned into plasmid vector pMSCV and sequenced. High-tiler recombinant retrovirus pMSCV-ANGPTLA and blank retrovirus pMSCV packaged under mediation of lipofectamine infected HepG2 cells in vitro, respectively. Flow cytometry and fluorescence microscopy detected expression of GFP (green fluorescence protein) in HepG2 cells. The expression of ANGPTL4 mRNA in HepG2 cells was determined. Results Recombinant retroviral vector pMSCV-ANGPTL4 was constructed successfully. Titer of recombinant retrovirus pMSCV-ANGPTL4 packaged is 1. 4 ? 106 infective viral grains /ml. Titer of blank retrovirus pMSCV packaged was 1. 5 ? 106 infective viral grains /ml. Positive cell rate of HepG2-ANGPTL4 cells group expressing GFP was 68.45% , and average intensity of fluorescence of HepG2-ANGPTL4 cells group was 31.67 -fold as that of HepG2 cells group. Positive cell rate of HepG2-pMSCV cells group expressing GFP was 77.72%, and average intensity of fluorescence of HepG2-pMSCV cells group was 64. 87 -fold as that of HepG2 cells group. The expression of ANGPTL4 mRNA in HepG2-ANGPTL4 cells group was higher than that in HepG2-pMSCV cells group (154%) and HepG2 cells group( 161%). The proliferation rate of HepG2-ANGPTL4 cells group in vitro was lower than HepG2-pMSCV cells group and HepG2 cells group (P

The effect of anti-oncogene p15, p16 on the proliferation of a human cholangiocarcinoma cell line / 中国普通外科杂志

ObjectiveTo study the effect of anti-oncogene p15 and p16 on the proliferation of human cholangiocarcinoma cell line.MethodsThe cDNA of anti-oncogene p15 and p16 was constructed into pcDNA3-neo plasmid carrier. The human cholangiocarcinoma cell line QBC939 were transfected with the recombinants pcDNA3p15 and pcDNA3p16 using lipofectin, respectively. The expression products were analyzed by Western blot. Cell viability and death were measured with MTT assay. Cell cycle was determined by flow cytophotometry and the formation of cell clone was detected. Results The growth of QBC939 cells was inhibited. The flow cytophotometry verified p15 and p16 induced QBC939 cell G1 blockade. Conclusion Anti-oncogene p15 and p16 together lead to the inhibition of cell cycle.

Biological effect of p27~(KIP1) on gastric carcinoma cells SGC7901 in nude mice / 中国普通外科杂志

Objective To determine the biological effect of p27 KIP1 on gastric carcinoma cells SGC7901. Methods The total length of p27 KIP1 cDNA was transfected into human gastric cancer cells SGC7901 by lipofectin transfection. Expression of p27 KIP1 in protein or mRNA level was examined by Western blotting and RNA dot blotting respectively. Effect of p27 KIP1 on cell growth was observed by trpan blue exclusion assay. Tumorigenicity test in nude mice was applied to assess the biological effect of p27 KIP1 in vitro. Results Expression of p27 KIP1 in protein or mRNA increased evidently in SGC7901 cells transfected with p27 KIP1 . The cell growth was reduced by 42% about 48h after the induction with Zn 2+ ,which was determined by cell viability assay. The tumorigenicity of nude mice was reduced evidently(P

Studying progression in gene p73 / 中国病理生理杂志

p73, a first p53 relative, has recently been identified as a new structural and functional homologue of the transcription factor p53. However, it is unclear whether this protein functions as a tumor suppressor. p73L, a second human p53-related gene, which shows strong amino-acid similarity to p73. In this article, we shall discuss the cloning, location, expression and functions of these two new candidate tumor suppressor genes and look forward to the future study.

MicroRNAs and liver cancer:recent progress / 第二军医大学学报

MicroRNA(miRNA)is a small non-coding RNA that contains 21 to 23 nucleotides and can down-regulate gene expression by translational repression.Recent studies found that some miRNAs might function both as oncogenes and tumor suppressors;its role in the tumorigenesis may complement and enrich the mechanisms of tumorigenesis.Liver cancer is a great threat to human health,whose pathogenesis is still not completely understood.MiRNAs can influence the tumorigenesis,differ- entiation and treatment of liver cancer.Here we summarizes the related progression in research of miRNA and liver cancer.