共查询到20条相似文献,搜索用时 312 毫秒
1.
Martin Heni J?rg Hennenlotter Marcus Scharpf Stefan Z. Lutz Christian Schwentner Tilman Todenh?fer David Schilling Ursula Kühs Valentina Gerber Fausto Machicao Harald Staiger Hans-Ulrich H?ring Arnulf Stenzl 《PloS one》2012,7(12)
Aims/Hypothesis
In different cancers types, insulin receptor isoform composition or insulin receptor substrate (IRS) isoforms are different to healthy tissue. This may be a molecular link to increased cancer risk in diabetes and obesity. Since this is yet unclear for prostate cancer, we investigated IR isoform composition and IRS balance in prostate cancer compared to benign and tumor adjacent benign prostate tissue and brought this into relation to cell proliferation.Methods
We studied 23 benign prostate samples from radical cystectomy or benign prostatic hyperplasia surgery, 30 samples from benign tissue directly adjacent to prostate cancer foci and 35 cancer samples from different patients. RNA expression levels for insulin receptor isoforms A and B, IRS-1, IRS-2, and IGF-1 receptor were assessed by quantitative real-time RT-PCR. In addition, RNA- and protein expression of the cell cycle regulator p27Kip1 was quantified by real-time RT-PCR and immunohistochemistry.Results
Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates (p<0.05). IRS-1 to IRS-2 ratios were lower in malignant than in benign prostatic tissue (p<0.05). These altered ratios both in cancer and adjacent tissue were significantly associated with reduced p27Kip1 content (p<0.02). Interestingly, IGF-1 receptor levels were significantly lower in patients with type 2 diabetes (p = 0.0019).Conclusions/Interpretation
We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy. 相似文献2.
Background
Identification of tumor heterogeneity and genomic similarities across different cancer types is essential to the design of effective stratified treatments and for the discovery of treatments that can be extended to different types of tumors. However, systematic investigations on comprehensive molecular profiles have not been fully explored to achieve this goal.Results
Here, we performed a network-based integrative pan-cancer genomic analysis on >3000 samples from 12 cancer types to uncover novel stratifications among tumors. Our study not only revealed recurrently reported cross-cancer similarities, but also identified novel ones. The macro-scale stratification demonstrates strong clinical relevance and reveals consistent risk tendency among cancer types. The micro-scale stratification shows essential pan-cancer heterogeneity with subgroup-specific gene network characteristics and biological functions.Conclusions
In summary, our comprehensive network-based pan-cancer stratification provides valuable information about inter- and intra- cancer stratification for patient clinical assessments and therapeutic strategies.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1687-x) contains supplementary material, which is available to authorized users. 相似文献3.
Yan Liu Fei Zhang Xiao-fang Zhang Li-sha Qi Lei Yang Hua Guo Ning Zhang 《Journal of biomedical science》2012,19(1):53
Background
We aimed to examine the expression level of Nucleophosmin (NPM1) protein in colon cancer tissues and to investigate the potential role of NPM1 in the regulation of cell migration and invasiveness.Methods
Immunohistochemical assay was performed to examine the expression pattern of NPM1 in 31 groups of colonic carcinoma samples, including colon tumors, adjacent normal tissues, and matched metastatic lymph nodes from the same patients. Small interfering RNA technique and exogenous expression of wild type NPM1 methods were used to further verify the function of NPM1.Results
High-expression of NPM1 correlates with lymph node metastasis (P = 0.0003) and poor survival rate of human colon cancer patients (P = 0.017). SiRNA-mediated reduction of NPM1 was also shown to inhibit the migration and invasiveness of metastatic colon cancer HCT116 cell line. In addition, the exogenous expression of NPM1 in HT29 cells, a NPM1 low expression and low invasive colon cancer cell line, enhanced cell migration and invasiveness along with increased cell proliferation.Conclusions
The current study uncovered the critical role of NPM1 in the regulation of colon cancer cells migration and invasion, and NPM1 may serve as a potential marker for the prognosis of colon cancer patients. 相似文献4.
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Background
Currently available methods for diagnosis and staging of prostate cancer lack the sensitivity to distinguish between patients with indolent prostate cancer and those requiring radical treatment. Alterations in key adherens (AJ) and tight junction (TJ) components have been hailed as potential biomarkers for prostate cancer progression but the majority of research has been carried out on individual molecules.Objective
To elucidate a panel of biomarkers that may help distinguish dormant prostate cancer from aggressive metastatic disease.Methods
We analysed the expression of 7 well known AJ and TJ components in cell lines derived from normal prostate epithelial tissue (PNT2), non-invasive (CAHPV-10) and invasive prostate cancer (LNCaP, DU145, PC-3) using gene expression, western blotting and immunofluorescence techniques.Results
Claudin 7, α –catenin and β-catenin protein expression were not significantly different between CAHPV-10 cells and PNT2 cells. However, in PC-3 cells, protein levels for claudin 7, α –catenin were significantly down regulated (−1.5 fold, p = <.001) or undetectable respectively. Immunofluoresence showed β-catenin localisation in PC-3 cells to be cytoplasmic as opposed to membraneous.Conclusion
These results suggest aberrant Claudin 7, α – and β-catenin expression and/or localisation patterns may be putative markers for distinguishing localised prostate cancer from aggressive metastatic disease when used collectively. 相似文献7.
Zhuochun Peng Karl Andersson Johan Lindholm Inger Bodin Setia Pramana Yudi Pawitan Monica Nistér Sten Nilsson Chunde Li 《PloS one》2014,9(10)
Background
Predicting the prognosis of prostate cancer disease through gene expression analysis is receiving increasing interest. In many cases, such analyses are based on formalin-fixed, paraffin embedded (FFPE) core needle biopsy material on which Gleason grading for diagnosis has been conducted. Since each patient typically has multiple biopsy samples, and since Gleason grading is an operator dependent procedure known to be difficult, the impact of the operator''s choice of biopsy was evaluated.Methods
Multiple biopsy samples from 43 patients were evaluated using a previously reported gene signature of IGFBP3, F3 and VGLL3 with potential prognostic value in estimating overall survival at diagnosis of prostate cancer. A four multiplex one-step qRT-PCR test kit, designed and optimized for measuring the signature in FFPE core needle biopsy samples was used. Concordance of gene expression levels between primary and secondary Gleason tumor patterns, as well as benign tissue specimens, was analyzed.Results
The gene expression levels of IGFBP3 and F3 in prostate cancer epithelial cell-containing tissue representing the primary and secondary Gleason patterns were high and consistent, while the low expressed VGLL3 showed more variation in its expression levels.Conclusion
The assessment of IGFBP3 and F3 gene expression levels in prostate cancer tissue is independent of Gleason patterns, meaning that the impact of operator''s choice of biopsy is low. 相似文献8.
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Nader Mansour Samaei Yaghoub Yazdani Reza Alizadeh-Navaei Hossein Azadeh Touraj Farazmandfar 《Journal of biomedical science》2014,21(1):73
Background
Aberrant DNA methylation as the most important reason making epigenetic silencing of genes is a main mechanism of gene inactivation in patients with colorectal cancer. In this study, we decided to identify promoter methylation status of ten genes encoding WNT negative regulators, and measure the expression of DNMT1 enzyme in colorectal cancer samples.Results
Aberrant methylation of APC gene was statistically significant associated with age over 50 (p = 0.017), DDK3 with male (p < 0.0001), SFRP4, WIF1, and WNT5a with increasing tumor stage (p = 0.004, p = 0.029, and p = 0.004), SFRP4 and WIF1 with tumor differentiation (p = 0.009 and p = 0.031) and SFRP2 and SFRP5 with histological type (p = 0.001 and p = 0.025). The increasing number of methylated genes correlated with the expression levels of the DNMT1 mRNA.Conclusions
The rate of gene promoter methylation of WNT pathway regulators is high in colorectal cancer cells. Hyper-methylation is associated with increased expression of the DNMT1 enzyme. 相似文献11.
Role of Raf-kinase inhibitor protein in colorectal cancer and its regulation by hydroxycamptothecine
Fang Nie Jianguo Cao Jinlu Tong Mingming Zhu Yuan Gao Zhihua Ran 《Journal of biomedical science》2015,22(1)
Background
Recently accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. However, studies investigating the role of RKIP in colorectal cancer have not been reported. The aim of this study was to investigate the role of RKIP on colorectal cancer cell differentiation, progression and its correlation with chemosensitivity.Results
Immunohistochemical analysis revealed that RKIP expression was higher in non-neoplastic colorectal tissue (NCRCT) and colorectal cancer tissue (CRCT) than that in metastatic lymph node tissue (MLNT) (P <0.05). P-ERK protein expression was higher in MLNT and CRCT than that in NCRCT (P = 0.02). Immunocytochemical analysis further revealed that RKIP expression was higher in the well differentiated cell line SW1116 as compared to that in the poorly differentiated cell line LoVo. Matrigel invasive assay demonstrated that the inhibition of RKIP by short hairpin RNA (shRNA) 271 transfection significantly increased the number of migrated cells (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.05), whereas over-expression of RKIP by PEBP-1 plasmid transfection significantly suppressed the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05). Meanwhile, down-regulation of RKIP induced an increase in the cell survival rate by inhibiting apoptosis induced by hydroxycamptothecine.Conclusions
RKIP was also found to be associated with cell differentiation, with a higher activity in well differentiated colorectal cancer cells than in poorly differentiated ones. The upregulated expression of RKIP in colorectal cancer cells inhibited cell invasion and metastasis, while downregulation of RKIP reduced chemosensitivity by inhibiting apoptosis induced by HCPT. 相似文献12.
Abdellatif Essabbani Luis Garcia Maria Josè Zonetti Tommaso Fisco Sabina Pucci Gilles Chiocchia 《PloS one》2013,8(2)
Background
In prostate cancer the secreted form of clusterin (sCLU) has been described as an anti-apoptotic protein whose expression is increased after therapeutic intervention, whereas, the nuclear protein form nCLU was reported to have pro-apoptotic properties.Methodology
In order to provide new therapeutic approaches targeting CLU, we developed a strategy based on exon skipping by using a lentiviral construct to preferentially induce the nuclear spliced form of the protein. The molecular construct was transduced in LNCaP cells for testing the modulation of sensitivity of the transduced cells to pro-apoptotic stress.Results and Conclusions
We showed an increase of nCLU/sCLU expression ratio in the prostate cancer cell line “LNCaP” after lentiviral vector-U7 nCLU transduction. Moreover, we showed a significant inhibition of cell proliferation in nCLU-U7 LNCaP cells after treatment with cisplatin and after exposure to ionizing radiation compared to control cells. Finally, we showed that nCLU-U7 LNCaP cells exposure to UV-C significantly reduced an increase of cell death compared to control. Finally, we showed that modulating nCLU expression had profound impact on Ku70/Bax interaction as well as Rad17 expression which could be a key mechanism in sensitizing cells to cell death. In conclusion, this is the first report showing that increasing of nCLU/sCLU expression ratio by using an “on demand alternative splicing” strategy successfully increased sensitivity to radiotherapy and chemotherapy of prostate cancer cells. 相似文献13.
Charles E. Birse Robert J. Lagier William FitzHugh Harvey I. Pass William N. Rom Eric S. Edell Aaron O. Bungum Fabien Maldonado James R. Jett Mehdi Mesri Erin Sult Elizabeth Joseloff Aiqun Li Jenny Heidbrink Gulshan Dhariwal Chad Danis Jennifer L. Tomic Robert J. Bruce Paul A. Moore Tao He Marcia E. Lewis Steve M. Ruben 《Clinical proteomics》2015,12(1)
Background
Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging.Results
We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21–1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775).Conclusions
Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.Electronic supplementary material
The online version of this article (doi:10.1186/s12014-015-9090-9) contains supplementary material, which is available to authorized users. 相似文献14.
Dogus Murat Altintas Nathalie Allioli Myriam Decaussin Simon de Bernard Alain Ruffion Jacques Samarut Virginie Vlaeminck-Guillem 《PloS one》2013,8(6)
Background
Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.Methods
ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1).Results and Discussion
By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94).Conclusions
We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools. 相似文献15.
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Bishnuhari Paudyal Pramila Paudyal Dilip Shah Hideyuki Tominaga Yoshito Tsushima Keigo Endo 《Journal of biomedical science》2014,21(1):35
Background
The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750.Results
Ex vivo analysis showed 2.1 ± 0.4%, 37.6 ± 6.3% and 38.5 ± 6.2% injected dose/g accumulated in the tumors at 15 min, 24 h and 48 h respectively. Tumor uptake was significantly decreased in pretreated with excess of bevacizumab (p = 0.002). Immunofluorescence analysis showed strong staining of anti-CD 31 antibody around the blood vessels. Anti-VEGF-A and bevacizumab showed heterogeneous expression throughout the tumor.Conclusions
Current study successfully detected the VEGF expression in HT29 colorectal cancer xenografts, signifying as a potential agent for non-invasive imaging of VEGF expression, which may be applied in clinical practice. 相似文献17.
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Fabrice Legeai Sylvie Gimenez Bernard Duvic Jean-Michel Escoubas Anne-Sophie Gosselin Grenet Florence Blanc Fran?ois Cousserans Imène Séninet Anthony Bretaudeau Doriane Mutuel Pierre-Alain Girard Christelle Monsempes Ghislaine Magdelenat Frédérique Hilliou René Feyereisen Mylène Ogliastro Anne-Nathalie Volkoff Emmanuelle Jacquin-Joly Emmanuelle d’Alen?on Nicolas Nègre Philippe Fournier 《BMC genomics》2014,15(1)
19.
Sung Hae Chang Jin Kyun Park Yun Jong Lee Ji Ae Yang Eun Young Lee Yeong Wook Song Eun Bong Lee 《Arthritis research & therapy》2014,16(4)
Introduction
Rheumatic diseases (RDs) are associated with different cancers; however, it is unclear whether particular cancers are more prevalent in certain RDs. In the present study, we examined the relative incidence of several cancers in a single homogeneous cohort of patients with different RDs.Methods
Patients (N = 3,586) diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM) or polymyositis were included. Cancer diagnosis was based on histopathology. The 2008 Korean National Cancer Registry served as the reference for calculating standardized incidence ratios (SIRs).Results
During the follow-up period of 31,064 person-years, 187 patients developed cancer. RA and SLE patients showed an increased risk of non-Hodgkin’s lymphoma (SIR for RA patients = 3.387, 95% confidence interval (CI) = 1.462 to 6.673; SIR for SLE patients = 7.408, 95% CI = 2.405 to 17.287). SLE patients also had a higher risk of cervical cancer (SIR = 4.282, 95% CI = 1.722 to 8.824). SSc patients showed a higher risk of lung cancer (SIR = 4.917, 95% CI = 1.977 to 10.131). Endometrial cancer was increased only in patients with DM (SIR = 30.529, 95% CI = 3.697 to 110.283). RA patients had a lower risk for gastric cancer (SIR = 0.663, 95% CI = 0.327 to 0.998). The mean time between the RD and cancer diagnoses ranged from 0.1 to 16.6 years, with the shortest time observed in patients with DM (2.0 ± 2.1 years).Conclusions
Different RDs are associated with particular cancers. Thus, cancer surveillance tailored to specific RDs might be beneficial.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0428-x) contains supplementary material, which is available to authorized users. 相似文献20.
Jun Kojima Jun Araya Hiromichi Hara Saburo Ito Naoki Takasaka Kenji Kobayashi Satoko Fujii Chikako Tsurushige Takanori Numata Takeo Ishikawa Kenichiro Shimizu Makoto Kawaishi Keisuke Saito Noriki Kamiya Jun Hirano Makoto Odaka Toshiaki Morikawa Hiroshi Hano Satoko Arai Toru Miyazaki Yumi Kaneko Katsutoshi Nakayama Kazuyoshi Kuwano 《Respiratory research》2013,14(1):30